NHMRC Research Achievements – Mental Health
END OF GRANT REPORTS
OUTCOMES OF NHMRC FUNDED RESEARCH INTO MENTAL HEALTH RELATED ISSUES
ENDING 2000 TO 2009
CONTENTS
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Dr Alan R Clough - Public Health (Australia)
Fellowship
Australian National University
Prof Bryan Rodgers - Project Grant Fellowship
Prof Anthony F Jorm - New Program Grant
A/Pr Kaarin J Anstey - Population Health CDA
Dr Peter J Butterworth - Public Health (Australia)
Fellowship
Prof Bryan Rodgers -NHMRC Research Fellow
Prof Helen M Christensen-NHMRC Research
Fellow
Baker IDI Heart and Diabetes Institute
Prof Murray D Esler - NHMRC Research Fellow
Dr Gavin W Lambert - Biomedical CDA
Prof Murray D Esler - Standard Project Grant
Curtin University of Technology
Prof Murray J Dyck - Standard Project Grant
Prof David A Hay - Standard Project Grant
Dr Ann M Williams-Australian Clinical Research
Fellowship
La Trobe University
Prof Alan Shiell - Standard
Project Grant
Dr Charles D Blaha - Standard Project Grant
Dr Melissa J Green -Australian Clinical
Research Fellowship
Mental Health Research Institute of Victoria
Prof Nicholas A Keks -Standard Project Grant
A/Pr Maarten van den Buuse-Standard Project
Grant
A/Pr Brian Dean -Standard Project Grant
Dr Murat Yucel - Standard Project Grant
Prof David L Copolov-Standard Project Grant
Prof David J Castle -Standard Project Grant
A/Pr Maarten van den Buuse-Standard Project
Grant
Menzies Research Institute TAS
Dr Kristy A Sanderson - Public Health
(Australia) Fellowship
Flinders University
Menzies School of Health Research NT
A/Pr Tracey D Wade - New Investigator
Dr Alan R Clough – NIDS 16
Dr Sheree J Cairney -Australian Clinical
Research Fellowship
Prof John T Condon - Standard Project Grant
Prof Mary A Luszcz - Standard Project Grant
Prof Bill W Blessing - Standard Project Grant
A/Pr Leon C Lack - Standard Project Grant
A/Pr Tracey D Wade - Standard Project Grant
Garvan Institute of Medical Research
Dr Ian P Blair – Peter Doherty Fellowship
Prof Peter R Schofield - Standard Project Grant
Griffith University
Prof Paula M Barrett - Standard Project Grant
Prof Alan Mackay-Sim - Standard Project Grant
Dr Sharon Dawe - Standard Project Grant
Prof Kim Halford - Standard Project Grant
James Cook University
A/Pr Komla Tsey - Standard
Project Grant
Monash University
A/Pr Benedict J Canny-Standard Project Grant
Prof Paul Fitzgerald -New Investigator
Prof Jayashri Kulkarni-Standard Project Grant
Prof Bruce J Tonge -Standard Project Grant
Prof Paul Fitzgerald - Standard Project Grant
Prof Bruce J Tonge -Standard Project Grant
Dr Britt Klein -Standard Project Grant
Prof Bruce J Tonge -Standard Project Grant
Prof Jayashri Kulkarni-Standard Project Grant
Dr Mark A Rogers- Neil Hamilton Fairley
Prof Arthur Christopoulos -Standard Project
Prof Jeff R Richardson -Standard Project
NHMRC Research Achievements - SUMMARY
Murdoch Children’s Research Institute
Prof John W Toumbourou -Standard Project
A/Pr Alasdair L Vance -Standard Project
Prof Anthony F Jorm- Standard Project
Prof Michael Berk- Standard Project
University of New England
Prof George C Patton - Standard Project
Dr Margaret L Brechman-Toussaint - New
Investigator
Queensland Institute of Medical Research
University of New South Wales
Dr Dale R Nyholt - Standard Project
Prof Nicholas G Martin - Standard Project
A/Pr Bryan J Mowry - Standard Project
A/Pr Maree R Teesson - NIDS 26
Prof Stewart L Einfeld - Standard Project
Prof Reginald F Westbrook -Standard Project
Prof Richard A Bryant - Standard Project
Prof Ian B Hickie - Epidemiology Project
A/Pr Skye McDonald - Standard Project
Prof Perminder S Sachdev - Standard Project
A/Pr Tony G Butler -Standard Project
A/Pr Maree R Teesson - Standard Project
A/Pr Jan Copeland - Standard Project
Prof Mark Dadds - Standard Project
Prof Gordon B Parker - New Program Grant
Prof Mark Dadds - NHMRC Research Fellow
Prof Susan C Kippax - Standard Project
Prof Reginald F Westbrook - Standard Project
Dr Janice M Fullerton -Howard Florey Fellow
Dr Gavan P McNally - Standard Project
Dr Adam J Guastella - Standard Project
Prof Richard A Bryant - New Program Grant
Prof Peter R Schofield - Standard Project
Prof Susan C Kippax - General Practice
Clinical Research
St. Vincent's Institute of Medical Research
Prof Michael W Parker - Standard Project
The Children's Hospital at Westmead
A/Pr Thiagarajan Sitharthan – NIDS 26
Turning Point Alcohol and Drug Centre
Dr Greg R Rumbold - Standard Project
University of Adelaide
Dr Rodney J Irvine - Standard Project
Prof Andrew A Somogyi - Standard Project
Prof Jason M White - Standard Project
Prof Michael G Sawyer - Standard Project
Prof Alexander C McFarlane - Standard Project
Prof Andrew A Somogyi - Standard Project
A/Pr Jozef Gecz - NHMRC Research Fellow
Dr Rodney J Irvine - Standard Project
Prof Jason M White - Standard Project
A/Pr Maria Makrides - Standard Project
University of Melbourne
Prof Christos Pantelis - Standard Project
Prof Patrick D McGorry - Standard Project
Prof Henry J Jackson - Standard Project
Prof George C Patton - Standard Project
A/Pr Sandra M Rees - Standard Project
A/Pr Brian Dean - Standard Project
Prof Patrick D McGorry - Standard Project
Prof Anthony F Jorm - NHMRC Research Fellow
Dr Lena A Sanci - Public Health Fellowship
Prof David L Copolov - Standard Project
Dr Andrew J Lawrence-NHMRC Research Fellow
Dr Mark A Bellgrove-Howard Florey Fellow
Prof Jane M Gunn - Standard Project
Dr Michelle A Kermode-Public Health Fellowship
A/Pr Brian Dean - Standard Project
A/Pr Jane E Pirkis- Population Health CDA
Prof Patrick D McGorry - New Program Grant
Dr Meghan L O'Donnell - Aust Clinical Reseach
Fellowship
A/Pr Terence J O'Brien - Standard Project
Dr Anthony J Hannan - Standard Project
University of Newcastle
A/Pr Amanda L Baker - Standard Project
A/Pr Amanda L Baker - Standard Project
Prof John AP Rostas - Standard Project
Prof Patricia T Michie - Standard Project
Prof Michael B Calford - Standard Project
A/Pr Ulrich A Schall - Standard Project
A/Pr Amanda L Baker - Clinical CDA
Prof Vaughan J Carr - Standard Project
Dr Christopher V Dayas -CJ Martin
Fellowship
A/Pr Ulrich A Schall - Standard Project
Prof Trevor A Day - Standard Project
Prof Brian Kelly - Standard Project
University of Queensland
Prof Susan H Spence - Standard Project
Dr Kathryn M Buller - Standard Project
Prof Justin A Kenardy - Standard Project
Prof Pankaj Sah - Standard Project
A/Pr Bryan J Mowry - Standard Project
Dr Elizabeth MJ Gillam - Standard Project
NHMRC Research Achievements - SUMMARY
Dr Guy N Elston - New Investigator
Prof Anthony F Jorm- Standard Project
Prof Jake M Najman - Standard Project
Prof Jake M Najman - Standard Project
Prof Stanley V Catts-Mental Health Early
Psychosis
Prof Perry F Bartlett - Transfer from BFI
Prof Ross McD Young - NIDS 26
Dr Tamara L Ownsworth- Public Health
Fellowship
A/Pr Bryan J Mowry - Standard Project
A/Pr Peter R Dodd - Standard Project
Prof John D Pettigrew - Development Grant
Dr Christopher E Jones - CJ Martin Fellowship
Prof Brian Key - Standard Project
Prof Justin A Kenardy - Standard Project
Dr Rodney L Rietze - New Investigator
Prof Ross Smith - Standard Project
Dr Andrew J Delaney - Standard Project
Prof David Kavanagh - Health Research
Partnership in Mental Health
Prof Perry F Bartlett - New Program Grant
Dr Rosa Alati - Public Health Fellowship
Dr Melissa R. Haswell-Elkins-Standard Project
A/Pr Linda J Richards - Standard Project
Dr Randal X Moldrich - CJ Martin Fellowship
University of Sydney
Prof Iain S McGregor - Standard Project
Dr Peregrine B Osborne - Standard Project
Prof Chris C Tennant - Standard Project
Prof Paul S Haber - Standard Project
Dr Brian I. O'Toole - Standard Project
Prof Michael Murray - Standard Project
A/Pr Thiagarajan Sitharthan - Standard Project
Prof Iain S McGregor - Standard Project
Prof Mark Onslow - NHMRC Research Fellow
Prof Iain S McGregor - Standard Project
Dr Kim L Felmingham - Australian Clinical
Research Fellowship
Dr Andrew H Kemp - Peter Doherty Fellowship
University of Western Australia
Prof Leon Flicker - Standard Project
Prof Gary K Hulse - Standard Project
Prof Nicola T Lautenschlager - Standard Project
Prof Gary K Hulse - Standard Project
Prof Assen V Jablensky - Standard Project
Prof Dieter B Wildenauer - Standard Project
Prof Osvaldo P Almeida - Standard Project
Prof Luba V Kalaydjieva - Standard Project
Prof Gary K Hulse - Standard Project
Prof Sergio E Starkstein - Standard Project
Dr David B. Preen - Standard Project
A/Pr Mathew T. Martin-Iverson - Standard
Project
NHMRC Research Achievements - SUMMARY
Australian National University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
148948
Prof Bryan Rodgers
Epidemiology
Australian National University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2005
$525,000.00
NHMRC Research Fellowship
Title of research award: NHMRC Research Fellowship
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Four main achievements were: 1) Adult psychological and social wellbeing was shown to be influenced by a wide
range of childhood family circumstances. The number of types of early adverity was more important than any
specific form of adversity, including apparently severe events such as physical and sexual abuse and family
separation. 2) Research on alcohol consumption and depression has shown consistently greater distress in
abstainers as well as heavy drinkers by comparison with people who are moderate drinkers. We have found
several characteristics of non-drinkers that help explain their heightened distress and depression but this does not
seem due to past history of alcohol use or abuse. 3) We found high rates of eating disordered behaviour in young
and middle-aged women in the general population and these behaviours are asociated with significant distress and
impaired quality of life. We believe that the public health significance of behaviours such as binge eating, laxative
use and vomiting has been underestimated and that attention has been focussed too narrowly on severe eating
disorders (anorexia and bulimia nervosa). 4) We have provided information on what forms of self-help and
complementary therapies are acceptable to the general public and which, therefore, can be used to prevent or
alleviate common mental health problems before they become sufficiently serious as to require specialist
professional treatment. These therapeutic approaches can be applied in non-medical settings and we have assisted
in the provision of information and advice in areas, such as the family law system, where service providers do not
have specialist mental health training or experience.
Expected future outcomes:
We are continuing our research in all of the above areas, with greater emphasis on informing policy development
and service provision. In the area of ill-health related to non-drinking, we are extending our research interests to
include physical health and morbity and well as psychological outcomes.
Name of contact:
Email of contact:
Bryan Rodgers
Bryan.Rodgers@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
179805
Prof Anthony F Jorm
Mental Health
Australian National University
Start Year:
End Year:
Total funding:
Grant Type:
2002
2006
$0.00
New Program Grant
Title of research award: Epidemiology of high prevalence mental disorders: Aetiology, course and public health
interventions
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
[1] Completion of two waves of the PATH through Life Project, with each wave taking more than 2 years to
complete. This project involves interviewing 7485 participants to obtain data on demographic, mental health and
cognitive functioning. Individuals are followed to identify risk factors for anxiety, depression, suicidal behaviour,
drug taking and cognitive performance at subsequent occasions. We have also completed clinical examinations
and MRI scans on a subset of the 60-64 year old cohort. From the MRI scans, volumes have been measured for
hippocampus, amygdala, entorhinal cortex, anterior cingulate, gray matter, white matter, CSF, total brain, and
regional white-matter hyperintensities have been quantified. Genotyping has been completed for several candidate
polymorphisms. [2] Development of a range of interventions to improve mental health literacy and reduce
symptoms of anxiety and depression. RCTs were conducted to establish the usefulness of Mental Health First Aid
Training, MoodGYM, BluePages and a written guide to effective treatments for depression. Trials have also been
conducted of web interventions in schools and in general practice settings. Surveys of mental health literacy in
adolescence, and for eating disorder were also completed, as well as a large national survey of mental health
literacy in Japan and Australia. A study of dementia health literacy was also completed.
Expected future outcomes:
The major epidemiological study funded by the Program Grant and the e-health component has secured NHMRC
funding through project grant support from 2006 and 2007.
Name of contact:
Email of contact:
Helen Christensen
helen.christensen@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
179839
A/Pr Kaarin J Anstey
Mental Health
Australian National University
Start Year:
End Year:
Total funding:
Grant Type:
2002
2006
$450,000.00
Population Health CDA
Title of research award: Antecedents and Consequences of Cognitive Decline and Depression in Later Life
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
A large range of research on risk factors for poor cognitive performance and brain aging was published. This work
was important because it included adults aged in their 20s, 40s and 60s, as well as adults in late life. Some risk
factors that have previously been associated with cognition only in late life, were found to be significant in young
adults. Factors examined included smoking, alcohol consumption, physical activity, HRT, and medical conditions.
Research also focussed on risk factors for suicidality and depression in late life and identified for example, that
older men who would like to be in the work force but are not, are at very high risk of suicidal ideation.
Psychological distress and potential cognitive impairment associated with visual impairment and cataract surgery
were also evaluated in a clinical trial. The first population-based study of mental health problems associated with
head injury in Australia was published. Further work investigated how cognitive decline in late life is associated
with falls in adults without cognitive impairment, and made recommendations that current screening instruments
for falling include brief cognitive measures. Other work focussed on driving cessation showing that health
perception is more important than actual medical conditions in predicting driving cessation, and that giving up
driving is associated with increased risk of depression.
Expected future outcomes:
Work in progress or submitted includes systematic reviews of risk factors for cognitive decline and dementia, an
evaluation of depression in relation to transition to residential care, and evaluation of subtle changes in brain
function associated with mild cognitive disorders.
Name of contact:
Email of contact:
Kaarin Anstey
Kaarin.anstey@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
316970
Dr Peter J Butterworth
Mental Health
Australian National University
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2005
2008
$264,000.00
Public Health (Australia)
Title of research award: Welfare receipt, social exclusion and mental health: exploring the relationship between
social disadvantage and mental health, and identifying and testing appropriate social policy responses.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The project explored the relationship between social disadvantage and common mental disorders and provided an
evidence base to inform ongoing welfare reform, and the design and delivery of appropriate interventions to
promote employment and social inclusion. The training award enabled the recipient to conduct a program of
epidemiological research investigating the social and economic consequences of mental disorders amongst
disadvantaged Australians and the identification of underlying risk and protective factors. The research examined
a number of different at-risk populations, including income support recipients, those experiencing unemployment,
caregivers, early-retirees, and those experiencing financial hardship. Aside from the peer-reviewed manuscripts
detailed below and presentations at international and national conferences, other project output included several
reports for government and presentations at national meetings of peak organisations in the social welfare and
employment areas. These presentations raised awareness and knowledge amongst policy makers and service
delivery agencies of important policy and service delivery implications of common mental disorders and will
promote better health outcomes. The project involved collaboration and policy-relevant research for a number of
Commonwealth government departments including Department of Families, Housing, Community Services and
Indigenous Affairs, and Department of Education, Employment and Workplace Relations.
Expected future outcomes:
Expected future outcomes include further publications in peer-reviewed journals. The recipient successfully
applied for a CDA fellowship which will further develop this research project with an increased emphasis on
evaluation of health services and the development of intervention options.
Name of contact:
Email of contact:
Peter Butterworth
Peter.Butterworth@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
366758
Start Year:
Prof Bryan Rodgers
End Year:
Public Health and Health Services not elsewhere classified
Australian National University
Grant Type:
2006
2008
Total funding: $572,500.00
NHMRC Research Fellowship
Title of research award: NHMRC Research Fellowship
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Achievements were in four main areas: (1) the public health significance of eating disordered behaviours in the
general population; (2) the importance of early life experiences for adult health; (3) the relationship between
employment and mental health; (4) the health of drinkers and abstainers. A series of publications from the Health
& Well-Being of Female ACT Residents Study highlighted the burden of eating-disordered behaviours in the
community even though the large majority of these do not meet criteria for formal diagnosis. Level of disability is
related to particular symptoms but individuals often do not recognise their problem or seek professional help.
Prospective and retrospective studies have quantified associations between childhood circumstances and adult
health. The relationship between childhood adversity and poor adult mental health is not explained by social
position in adulthood. Insecure employment, as well as higher job demands and lower control over work activities,
is associated with poorer mental health. The mental health of those working in jobs combining insecurity with
high demands and low control is as poor as the mental health of unemployed people. Men who retire early have
poor mental health initially but are similar to later retirees by the time they reach age 65. Abstainers as well as
heavy drinkers have poorer health than moderate drinkers. Research in this field should not concentrate on
lifetime abstainers, as self-reported lifetime abstinence is highly inaccurate. Comparisons between abstainers and
moderate drinkers should make allowance for past heavy drinking in both groups not just the former group.
Expected future outcomes:
We are conducting interventions to improve eating disorder mental health literacy in the community. We are
continuing research on childhood adversity, including abuse, and adult health. Research on employment and
mental health now utilises longitudinal data. We are investigating factors such as social relationships as possible
reasons for poor health of non-drinkers.
Name of contact:
Email of contact:
Bryan Rodgers
bryan.rodgers@anu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
366781
Prof Helen M Christensen
Mental Health
Australian National University
Title of research award: NHMRC PRF
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The Fellowship was renewed with promotion in 2009 to SPRF
Expected future outcomes:
The research projects will continue
Name of contact:
Email of contact:
Helen Christensen
Helen.Christensen@anu.edu.au
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$713,750.00
NHMRC Research Fellowship
NHMRC Research Achievements - SUMMARY
Baker IDI Heart and Diabetes Institute
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
182810
Prof Murray D Esler
Autonomic Nervous System
Baker IDI Heart and Diabetes Institute
Start Year:
End Year:
Total funding:
Grant Type:
2000
2004
$650,000.00
NHMRC Research Fellowship
Title of research award: NHMRC Senior Principal Research Fellowship
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Achievements were made in several areas relevant to health: 1. The way in which blood pressure is elevated in
overweight people has been worked out. A stimulant division of the automatic section of the nervous system, the
sympathetic nervous system, is activated in obesity, particularly involving the nerves passing to the kidneys.
Through changing the kidney's control of how much salt is in the body, this raises blood pressure. The research
illustrates the potential value of two non-drug hypertension treatments in obesity, exerise training and dietery
calorie restriction, both of which inhibit the excessive activity of the nerves to the kidney such as to lower blood
pressure. Further, the research suggests that a new class of blood pressure lowering drug, the "Imidazoline-binding
agents", which inhibit the sympathetic nervous system, are ideally suited for use in overweight people with high
blood pressure. At present the entry of this class of antihypertensive drug into use in Australia is inexplicably
being prevented by the Government. 2. The importance of mental stress and psychiatric illness of several types
(including depressive illness) as a cause of heart attack was proven. Depressive illness is now regarded as an
important heart "risk factor", right up there with high blood cholesterol, diabetes , smoking and high blood
pressure in its importance. Treating depression well has become part of heart attack prevention clinical care.
Expected future outcomes:
1. Knowledge of the body stress processes conveying heart risk in patients with panic disorder should lead to
better preventive care of panic sufferers, by allowing specific drug targeting of these abnomal nervous system
mechanisms which damage the heart. 2. The new class of blood pressure-lowering drugs, Imidazilone binding
agents, will specifially target obesity-related hypertension.
Name of contact:
Email of contact:
Professor Murray Esler
murray.esler@baker.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
182829
Dr Gavin W Lambert
Psychiatry
Baker IDI Heart and Diabetes Institute
Start Year:
End Year:
Total funding:
Grant Type:
2002
2006
$400,000.00
Biomedical CDA
Title of research award: RD Wright Career Development Fellowship
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
There is strong evidence that patients with major depressive disorder (MDD) are at increased risk of developing
coronary heart disease. While the mechanism of increased cardiac risk attributable to MDD at this stage is not
completely known my investigations indicate the importance of neuronal (particularly sympathetic nervous
overactivity) processes in the generation of cardiac risk. In a range of clinical contexts stimulation of the cardiac
sympathetic outflow has been demonstrated to contribute to myocardial infarction, ventricular arrhythmias and
sudden death. Activation of the sympathetic outflow to the heart is common in patients unexpectedly developing
ventricular tachycardia and ventricular fibrillation outside hospital. In heart failure there is similarly a high level
of stimulation of the cardiac sympathetic nerves, which has been directly linked to the development of ventricular
arrhythmias and sudden death. Using methods developed in our laboratory we found that sympathetic activity in
patients with MDD followed a bimodal distribution, some values being very high. Indicative of a defect in
function of the noradrenaline transporter (the protein that stops the action of noradrenaline released from nerves)
the extraction of tritiated noradrenaline by the heart was substantially reduced in patients with MDD.
Antidepressant therapy, using a serotonin specific reuptake inhibitor (SSRI), abolished the excessive sympathetic
activation seen in patients with MDD. In this study I have identified a subset of patients with MDD in whom
sympathetic activity is extraordinarily high, treatment with an SSRI reduces sympathetic activity in a manner
likely to reduce cardiac risk.
Expected future outcomes:
There is a clear need to identify the underlying neurochemical mechanisms responsible for MDD and their linkage
to the heart and vascular system. Further knowledge of the mechanisms responsible for generating cardiac risk
may pave the way for novel and perhaps relatively simple therapeutic strategies to be administered in those with
MDD in order to modify cardiac risk.
Name of contact:
Email of contact:
Gavin Lambert
gavin.lambert@baker.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
367606
Prof Murray D Esler
Mental Health
Baker IDI Heart and Diabetes Institute
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$445,875.00
Standard Project Grant
Title of research award: Panic Disorder: neurobiology and mechanisms of cardiac risk
Lay Description (from application):
Some people are subject to episodes of recurring, often inexplicable anxiety which are very unpleasant and
accompanied by physical symptoms such as sweating, palpitations, tremor and a sensation of suffocation.
Recurring attacks over a period of months, or years, forms the basis for the diagnostic of "panic disorder". It has
until recently been felt that although panic disorder was distressing and disabling, it did not constitute a risk of
life. Sufferers often fear that they have heart disease, because of the nature of their symptoms, but have been
reassured that this is not the case. Recent epidemiological studies, however, indicate that there is an increased risk
in patients with panic disorder. Our hypotheses in this research project are as follow: That some specific genes
predispose to the development of panic disorder - through actions on the nervous system and blood vessels and
that drug treatment (selective serotonin uptake blockers) and psychological treatment (cognitive behaviour
therapy, CBT) reduce cardiac risk in panic disorder. We will test these hypothesis using state of the art clinical
scientific methods. Panic disorder has an important cardiological dimension which needs to be better understood
for cardiac protection to be achieved in panic disorder patients.
Research achievements (from final report):
Panic disorder is a psychologically disabling condition, but additionally, in some sufferers carries a risk of heart
attack, disorders of heart rhythm and sudden death. This research was directed at trying to understand the
mechanisms of heart risk. The findings are: (i) An automatic stimulant system of the nervous system, the
sympathetic nervous system, is markedly activated during panic attacks; (ii) Panic disorder sufferers have a
problem of gene control, an "epigenetic" disorder, involving the noradrenaline transporter gene, which controls the
body mechanism for neutralizing the chemical messenger when is released from sympathetic nerves. This
intensifies the stimulation of the heart during panic attacks, adversely enhancing the stress response in the heart;
(iii) Panic disorder patients have very high rates of release of serotonin by brain neurons (the presumed chemical
basis of the disorder)
Expected future outcomes:
Identification of panic disorder sufferers at heart risk (these are a minority of patients) and provision of
pharmacological cardiac protection, directed at these demonstrated mechanisms of heart risk.
Name of contact:
Email of contact:
Professor Murray Esler
murray.esler@bakeridi.edu.au
NHMRC Research Achievements - SUMMARY
Curtin University of Technology
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
141107
Prof Murray J Dyck
Health, Clinical and Counselling Psychology
Curtin University of Technology
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$263,311.27
Standard Project Grant
Title of research award: Direct and indirect assessment of 5 ability structures underlying 7 categories of
childhood psychopathology
Lay Description (from application):
This research has four main aims. First, we aim to obtain detailed knowledge of how normal children develop a
range of different abilities, including motor coordination, language skills, the ability to understand other people,
self-control, and general cognitive ability. Second, with this knowledge of normal development we will be able to
identify cases in which normal development does not occur and to identify the exact ability area(s) in which
development is abnormal. Patterns of abnormal development will be studied in children with one of seven
disorders, including Autistic Disorder, Intellectual Disability, and Developmental Coordination Disorder. Third,
we will assess whether deficits in some ability correspond to impairments in just one basic psychological structure
(e.g., language deficits are related to impairment in the ability to recognise sounds) or whether they can be due to
impairments in several structures (e.g., the ability to recognise faces or the ability to maintain attention). Finally,
we will investigate whether and how impairments in one or more basic psychological structures can result in
deficits in one or more of the ability areas that are the basis for the diagnosis of one or more developmental
disorders. This research is expected to lead to an enhanced ability to assess the exact nature of any given
developmental disorder which, in turn, should enhance clinical care of the child.
Research achievements (from final report):
This research will contirbute to changing and improving the way in which developmental disorders are diagnosed
and defined. The research clearly demonstrates what problems children with ostensibly different disorders have in
common with each other and also demonstrates the relative strengths that distinguish children with one disorder
from children with other disorders. The research suggests that the way different neocognitive structures interact
with each other is what is primarily affected in developmental disorders, and understanding exactly which
interactions have been affected, and how they have been affected, is the ley task for future research.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
229005
Prof David A Hay
Mental Health
Curtin University of Technology
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$557,500.00
Standard Project Grant
Title of research award: Solving the jigsaw! Understanding biological and environmental effects on ADHD
through discordant monozygotic twins
Lay Description (from application):
The recent Child and Adolescent component of the National Mental Health Survey identified Attention Deficit
Hyperactivity Disorder(ADHD) as the most common behavioural problem among Australian children. Since 1991
our Australian Twin ADHD Project (ATAP) has developed as one of the world's largest programs on the genetics
of ADHD, and in 2001 we published the first text on this topic. In this grant we turn the focus onto environmental
influences with the question "Why can one identical twin have ADHD, while the other twin has no difficulties?"
Using the unique resources of the Australian Twin Registry and the WA Twin Child Health Study, we shall work
across the country to find over 100 identical twin pairs who are very different in ADHD. In this way, each ADHD
affected twin has an unaffected 'control twin', offering a powerful means for comparing the two. Such a study is
really only possible in Australia, as no other country has such twin resources for research. The questions we want
to consider with these children include the following 1/ Twins have a more difficult time before and at birth. To
what extent do these problems contribute to differences between the twins? 2/ Are there differences in specific
aspects of brain functioning? 3/ Is it that one twin grows out of their ADHD but the other does not? If so, what
distinguishes the children? 4/ What is it like growing up with a twin who has ADHD, when you have no
difficulties yourself? 5/ When one twin has ADHD symptoms, is the family more likely to seek help, as they can
see how different this child is form the other twin? Obviously identical twins in wehich only one has ADHD are a
very unique group. By covering all aspects of development, from brain functioning to service utilisation, the hope
is that this study will provide invaluable insights into this common condition which will help all children and
families where the diagnosis of ADHD has been made.
Research achievements (from final report):
ADHD remains a controversial diagnosis. This project has achieved in four main areas (1) understanding the
range of conditions which often are comorbid with ADHD ,which must be considered in best practice and which
add credence to the diagnostic label of ADHD, (2) appreciating the causes of such comorbidity e.g. children with
ADHD often have reading problems not as a consequence of ADHD but because the same genes determine both,
(3) identifying some of the obstetric and other issues which may contribute to one identical twin but not the other
having ADHD, and (4) for the first time, alerting workers to the problems such as anxiety facing children who
have a sibling with ADHD. This project will lead to better practice in treating ADHD children and supporting
their families in this, the most common behavioural disorder in Australian children.
Expected future outcomes:
Improved understanding by clinicians and the community about ADHD. Our new NIMH grant to determine more
about the genes in ADHD Our new role as the world centre for the sharing of information among ADHD
researchers
Name of contact:
Email of contact:
Professor David Hay
d.hay@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
274906
Dr Ann M Williams
Health, Clinical and Counselling Psychology
Curtin University of Technology
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2004
2007
$259,000.00
Australian Clinical Research
Title of research award: The devlopment and testing of an instrument to measure the personal control and
associated emotional comfort needs of hospitalised patients
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Reduced personal control has been identified as a source of psychological distress in hospitalised patients. The
manner by which hospital staff interact with patients is a factor that can influence a person's perception of personal
control. This project developed a new instrument that evaluated the emotional care provided by staff to patients in
the form of interactions. The instrument was a questionnaire designed to be completed by hospitalized patients.
Preliminary testing of this instrument was carried out initially on a cancer ward, and then across an acute care
private hospital producing encouraging results. Emotional care delivery on the cancer ward was measured using
the instrument and found to be improved by using a coordinated research-based educational approach led by a
clinical champion. However, levels varied during the project and factors such as the emotional distress of the staff
were indicated as impacting on the quality of emotional care delivered to patients. Further testing of this
instrument in different patient populations is recommended. Health care providers are challenged by how to best
allocate limited resources and it is essential that appropriate, cost-effective strategies are developed to address
differing needs. It was found that this instrument could be used to identify patients who may be in most need of
additional emotional care. The instrument could also be used to test various interventions aimed at improving the
emotional wellbeing of patients in hospital.
Expected future outcomes:
This project has highlighted the complexity of emotional care. Future work will focus on the evaluation of
different interventions to promote emotional wellbeing in hospitalised patients. This will include further testing of
the instrument and investigation into the impact of the emotional wellbeing of hospital staff on emotional care
delivery.
Name of contact:
Email of contact:
Anne Williams
Anne.Williams@curtin.edu.au
NHMRC Research Achievements - SUMMARY
Flinders University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
160009
A/Pr Tracey D Wade
Psychiatry
Flinders University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$225,000.00
New Investigator
Title of research award: An investigation of the aetiology of eating disorders: interactions between genes and
environmental risk factors
Lay Description (from application):
Eating disorders, along with substance abuse, carry the highest risk of premature death, from both natural and
unnatural causes, out of 27 mental disorder categories. Eating disorders, including anorexia nervosa, bulimia
nervosa, and binge-eating disorder, affect about 6% of Australian women. Despite increased levels of research
into the aetiology of eating disorders over the last 20 years, little knowledge exists as to which risk factors cause
women to attempt weight loss to the point of increasing their risk of premature mortality. A review of twin studies
in eating disorders concludes that there is increasing evidence to suggest that genetic factors play a role in the
development of eating disorders. In addition, a recent series of studies, examining risk factors before the age of
eating disorder onset, have found the following events to specifically predict the development of an eating
disorder as opposed to another psychiatric condition: negative self-evaluation, parental alcoholism, low parental
contact and high parental expectations, critical comments about weight, shape or eating during childhood, and
childhood obesity. To date, no studies have attempted to integrate the findings from twin studies with the findings
from early risk factor studies. Specifically, the ways in which genes interact with the environment to increase the
chances of genetic vulnerability to an eating disorder being expressed have not been examined. The proposed
project seeks to investigate precisely these interactions between genes and the environment, by examining a large
number of female twins, aged 29-37. An enhanced understanding of how genes interact with the environment to
either increase the chances that a woman will develop an eating disorder, or alternatively to protect a woman from
developing an eating disorder, will benefit our understanding of how to target prevention and treatment strategies.
Research achievements (from final report):
Over the three-year period of the grant, a total of 6728 female twins from the Australian Twin Registry were
approached to participate in this study. Participation entailed filling out a self-report questionnaire about a number
of issues relating to current mental health and experiences in the family when growing up, and either a telephone
interview or a self-report questionnaire about any experience of eating disorders over the woman's lifetime. Of the
women approached, 2021 agreed to participate in the study, resulting in the completion of 1287 interviews and
633 self-reports on eating disorders. This database represents the only one in the world that has used an extensive
interview about eating disorders and thus gives us a rich source of data to examine an extensive list of questions.
The first few questions that will be addressed in scientific publications are: (1) does the environment affect the
severity of the eating disorder? (2) is our current diagnostic criteria for eating disorders the best way of
summarising the experience that women have with disordered eating? (3) what specific sources of environment
might increase genetic susceptibility to developing an eating disorder? (4) do the different types of eating
disorders (e.g., anorexia nervosa, bulimia nervosa) share a common genetic susceptibility? The potential benefits
of this research will be twofold. First, clarification of the types of disordered eating that represent clinically
significant problems will inform treatment guidelines and treatment eligibility criteria. Second, identification of
the types of environment that should be targeted for intervention will enable us to have a maximum impact on
protecting women from the development of an eating disorder.
Expected future outcomes:
The findings of the study will be published in a series of papers in international scientific journals. The ultimate
impact of this work will be on the classification of eating disorders and also on the identification of strategies that
can target environmental risk factors in order to modify genetic risk for developing an eating disorder.
Name of contact:
Email of contact:
Tracey Wade
tracey.wade@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
160017
Prof John T Condon
Psychiatry
Flinders University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$170,000.00
Standard Project Grant
Title of research award: Adolescent Males' beliefs and feelings about the consequences of a partner's pregnancy:
a survey and intervention study
Lay Description (from application):
Each year, in Australia, approximately 28,000 adolescents become pregnant. The psychological, social and
financial cost of adolescent pregnancy in Australia is substantial, in both the long and short term. An unexpected
finding in North American studies is that a substantial number of adolescent pregnancies occur by design.
Prevention programs in Australia and elsewhere assume adolescents do not wish to become pregnant and focus on
educating adolescents about "causes" rather than "consequences". Research conducted by one of us (JAQ) found
that over 75% of pregnant teenagers said they had deliberately become pregnant. Another of us (JTC) studied
1,500 Australian adolescents attitudes and beliefs about pregnancy and parenthood. The findings showed high
levels of idealisation, especially in males. Males have been largely neglected in adolescent pregnancy research.
The first component of this study is a survey of 500 adolescents to investigate their attitudes and beliefs about
pregnancy occurring in a sexual partner, and the consequences of that event for them both. The assessment tool is
a computer role-play simulation with its starting point the announcement of a pregnancy. The intervention study
involves 300 adolescents and comprises viewing and discussing a video in which 4 adolescent males talk about
their experiences of the consequences of pregnancy in a sexual partner. The use of 4 groups with different
sequences of assessment and intervention will enable us to ascertain the effectiveness of the intervention. Of
particular interest is whether the video or the role-play makes any impact on idealised attitudes and beliefs. This
research is the first undertaken on adolescent male attitudes and beliefs using a computer role-play. It will provide
essential information for the development of effective, male-oriented prevention programs which focus on
consequences as well as causes of adolescent pregnancy.
Research achievements (from final report):
The incidence of unplanned teenage pregnancy continues to pose a threat to the well-being of young people,
through pregnancy terminations and teenage births. The CD Rom measure and role-play intervention "If I were
Ben…" has both given a voice to young men's feelings and beliefs about the impact of an announced pregnancy,
and has provided a 'lived experience" to act as a deterrent. The adolescent males aged on average 15 years old
generally presented an idealised approach to teen fatherhood, with 30% choosing hypothetically to "keep the
baby". However when asked to evaluate the CD Rom intervention, 70% of the young men said the program had
made them think about new issues, think they should never get into a situation where they could be a teenage
father, and helped them understand the effect of a pregnancy on themselves. 60% became very involved in the
role-play situation. The response to the program by teachers and students strongly indicated that computerised and
multimedia interventions and surveys are far more attractive and accessible to young people than traditional
methods
Expected future outcomes:
The successful reception of the interactive CD ROM role -play game in schools, among adolescent males and their
teachers, indicates the utility of this approach to preventive health education. Future versions could include
extended cultural variety, a version for girls and versions covering other adolescent behaviour putting health at
risk.
Name of contact:
Email of contact:
Carolyn Corkindale
carolyn.corkindale@rgh.sa.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
229922
Prof Mary A Luszcz
Public Health and Health Services nec
Flinders University
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$385,000.00
Standard Project Grant
Title of research award: Late life transitions and pathways to healthy ageing
Lay Description (from application):
The rapid ageing of the oldest-old segment of the population calls for a concerted effort to determine the ways to
healthy ageing. This project aims to identify ways in which older adults deal with key transitions or points of
major change that occur in late life. Such transitions or events might include widowhood, change in living
arrangements, or ceasing to drive. They may pose a challenge to healthy ageing if ones choice of a coping strategy
is poor, others are not available to assist during the transition, or thinking and health problems are extensive. We
plan to extend an existing longitudinal study that commenced in 1992 with 2087 adults, mostly over the age of 70.
Repeat interviews and assessments of surviving participants (numbering about 800) will be completed, covering a
wide range of social, health, psychological and functional domains. In addition, we intend to identify participants'
particular transitions on the basis of previously collected data or incidents arising since we last saw them. A series
of questions will be devised to gain more information concerning perceptions of these transitions, how they
responded to them and what their impact was. We are interested in the consequences for the individual participant,
those with whom they associate and the health care system more broadly. Hence the second part of the research
strategy involves seeking information from other informants known to the ALSA participant and identified by
them at baseline. The final component is to gather relevant additional data (e.g., from Health Insurance
Commission files) to determine wider implications of transitions for social networks and health care systems. The
outcomes include a better understanding of which transitions are most consequential for healthy ageing; how to
effectively use existing resources to maintain or enhance healthy ageing; and the interpersonal and societal
implications of transitions. (1940 characters with spaces)
Research achievements (from final report):
The project comprised the 7th wave of Australian Longitudinal Study of Ageing and the 4th multidisciplinary
home interview and evaluation, augmented by secondary data from informants, the Health Insurance Commission
(HIC) and service providers. It aimed to understand how major transitions occurring late in life are negotiated by
individuals and facilitated by social and family networks and access to health care. Participants (N=487
Interviewed + 395 Objective Assessments; Informants n=449; HIC & Service Providers' data n=438) reported 400
transitions in the previous 3 years. Particular attention was focused on social networks, and their protection against
transitions in disability, death and relocation to residential care. Family networks are crucial in protecting against
disability, while friends have a stronger role in deterring death. Cognitive factors, rather than physiological ones,
were shown to be more important in protecting against falling and driving cessation. These findings have
significant benefits for practice and policy development. In the case of social networks, interventions could focus
on facilitating maintenance or renewal of acquaintances with friends and support for families with ageing
members. Cognitive screening should form an integral part of screening for driving continuation and the
likelihood of falls. Our examination of characteristics of the oldest old cohort revealed many examples of
resilience in the face of losses and late life disabilities. Case studies of these individual could form the basis of
public awareness campaigns aimed at better informing attitudes toward ageing. Publications and conference
presentations provide a further indication of the breadth of the study.
Expected future outcomes:
rther mining of ALSA data for policy relevant evidence on ageing well is substantial. ALSA data also are central
to the successful AWAP project 410215, and will be pooled with other Longitudinal Ageing Studies to develop
best practice models of how to compress morbidity and optimize healthy and productive ageing.
Name of contact:
Email of contact:
Mary Luszcz
mary.luszcz@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
187616
Prof William - Bill W Blessing
Psychiatry
Flinders University
Start Year:
End Year:
Total funding:
Grant Type:
2002
2006
$870,000.00
Standard Project Grant
Title of research award: Brain and skin blood flow: new animal model for understanding psychiatric disorders
and evaluating psychotropic agents.
Lay Description (from application):
We suddenly become pale when we get a fright; cutaneous blood vessels are linked to psychological function. The
skin vessel constriction response occurs because special neurochemical pathways in the brain send messages to
the spinal cord, and from there messages traverse peripheral sympathetic nerves to constrict the blood vessels in
the skin. By measuring skin blood flow in the rabbit ear and the rat tail we have been able to discover the major
brain pathway by which the constrict-the-skin-blood-vessels message reaches the spinal cord. The pathway
involves the amygdala, a forebrain region important in emotional expression and the raphe nuclei in the medulla
oblongata. Drugs which affect psychological function also effect skin blood flow. Ecstasy, the street drug used to
induce euphoria also constricts the skin vessels, and, sadly, the body temperature may increase so much that death
ensues. Ecstasy vigorously constricts the skin blood vessels in rabbits, and temperature increases. Ecstasy is
thought to act on serotonin-containing nerve cells in the brain, releasing serotonin (5-HT) onto special 5-HT2A
receptors. Activation of these receptors affects both psychological function and skin blood flow. Modern drugs
used to treat schizophrenia, so called atypical antipsychotics like clozapine and olanzapine, are thought to act as
antagonists at 5-HT2A receptors in the brain. We were thus very excited when we discovered in our rabbit model
that clozapine reverses the skin vasoconstriction induced by ecstasy. This means that we have specific hypotheses
concerning the actual brain pathways and neurotransmitters whereby ecstasy and clozapine exert their effects on
skin blood flow. Elucidating these pathways in rabbits and rats will provide solid knowledge concerning the
mechanism of action of the atypical antipsychotics, and it may well prove possible to use our animal model to
predict whether proposed new antipsychotic agents will be therapeutically effective.
Research achievements (from final report):
Our project has illuminated the role of the lower brainstem in the CNS pathway regulating cardiac function during
psychological stress and during fever. We have demonstrated that clozapine, a drug important in schizophrenia
treatment, profoundly and selectively inhibits neuronal activity involved in cutaneous body temperature
regulation, at rest and when this outflow is activated by exposing the animal to cold, by adminitering the
psychoactive drug MDMA (ecstasy) or the fever causing agent lipopolysaccharide, or by subjecting the animal to
apparently minor non-noxious alerting stimuli (eg tapping on the cage). We have made significant advances in
understanding the neurotransmitter receptor mechanisms involved in CNS control of body temperature, and this
knowledge will form a framework for elucidating the specific neural pathways involved in clozapine's effect on
vasoconstriction, a framework that we believe relevant to its therapeutic actions. We have illuminated brain and
spinal cord pathways involved in thermoregulatory mechanisms in rabbits and rats. We determined that the
conduction velocity of neurons regulating body temperature in the ear pinna in rabbits is not more than 1m/s, ie
they are unmyelinated. Our work provides stong evidence that serotonin synthesising neurons are part of the
population of brainstem neurons controlling cutaneous body temperature reulation. In conscious rabbits we have
demonstrated that inhibition of neuronal function in the brainstem region completely abolishes alerting responses,
adding to the overall picture of CNS control by a neural pathway descending from the amygdala and relaying in
the lower brainstem.
Expected future outcomes:
We have provided a neuroanatomical framework for integration of the neuropharmacological mechanisms
whereby clozapine affects neuronal activity involved in body temperature regulation. As we increase our
knowledge of how clozapine works, we should also gather clues as to the nature of the brain malfunctions that
result in schizophrenia.
Name of contact:
Email of contact:
Professor Bill Blessing
w.w.blessing@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
275564
A/Pr Leon C Lack
Health, Clinical and Counselling Psychology
Flinders University
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$264,750.00
Standard Project Grant
Title of research award: Evaluation of a rapid behavioural treatment for sleep onset insomnia
Lay Description (from application):
Chronic insomnia is a prevalent health problem that affects 5-10% of the population. It is associated with
significant physical and mental health problems as well as lowered quality of life. By far the most common
treatment for insomnia continues to be sleeping tablets despite the problems of drug dependence, daytime
impairment and long term loss of effect. It is also despite the evidence that behavioural therapies are more
effective in the long term. In clinical experiments stimulus control therapy (SCT) is consistently the most effective
of the behavioural therapies. However, SCT is difficult to carry out over the 4-6 week period necessary for
effective treatment. If the treatment process could be shortened, it may increase the number of successful
treatments. We have developed a laboratory procedure which includes the effective elements of SCT. These
elements include sleep restriction and the experience of one rapid sleep onset each night. Our procedure involves
some sleep deprivation and the experience of many (over 40) rapid sleep onsets over just one day. Therefore, it
condenses 40 nights of the re-training benefits of SCT into just one day. A preliminary study has shown this
procedure to be as effective as normal SCT. However, with no follow-up therapy to the procedure the initial gains
tended to diminish with time. Our proposal is to test and extend the possible benefits of this new treatment
procedure. We will compare it with the standard SCT as well as combine it with SCT. We feel that the greatest
benefit may be to use the laboratory procedure as a "kick start" to SCT, which will by-pass the most difficult first
2--3 weeks of SCT. This will greatly reduce the time as well as absolutely improve the outcome. In further studies
the laboratory procedure may be transferred to the patient s home, thereby further increasing its effectiveness. We
feel the proposal will lead to a significant improvement in the non-drug treatment of insomnia.
Research achievements (from final report):
Chronic severe insomnia is a prevalent (5-10%) debilitating condition with significant societal and economic
burden. Although Behavioural therapies are effective for the treatment of chronic insomnia, their relatively slow
response rate can discourage compliance and reduce effectiveness. The research project tested the effectiveness of
a novel brief but intensive treatment procedure in comparison and in combination with standard treatment. The
procedure, called intensive sleep re-training (ISR), consisted of a 26 hour period of sleep deprivation to ensure
rapidly falling asleep. Half-hourly opportunities to fall asleep gave the insomnia participants at least 45
experiences of falling asleep quickly during this procedure. This was shown to be effective treatment on its own
for chronic insomnia. When combined with standard treatment it was more effective than either alone and
provided a rapid and sustained improvement in sleep and daytime functioning more effective than drug therapy.
ISR in combination with standard cognitive/behavioural therapy promises to advance the treatment of chronic
insomnia and provide even better outcomes for sleep and daytime functioning that can be obtained with current
therapies.
Expected future outcomes:
The main disadvantage of this therapy is cost for laboratory time. This may be reduced with the simultaneous
treatment of several patients in a sleep laboratory. Alternatively, new technology now available may be able to
awaken patients at PSG sleep onset to allow home based implementation of the therapy.
Name of contact:
Email of contact:
Leon Lack
leon.lack@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
324715
A/Pr Tracey D Wade
Mental Health
Flinders University
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$263,500.00
Standard Project Grant
Title of research award: Risk Factors for the development of eating disorder phenotypes and endophenotypes in
adolescent twins
Lay Description (from application):
The overall aim of the project is to develop a better understanding of how environment, temperament and genes
work together to cause disordered eating and eating disorders. Eating disorders, including anorexia nervosa and
bulimia nervosa, are an extremely difficult and costly condition to treat, and are associated with high mortality.
Eating disorders in adolescence lead to increased risk for anxiety disorders, chronic fatigue, chronic pain,
depressive disorders, infectious diseases, suicide attempts, and limitation in activities due to poor health in
adulthood. Full- and partial-syndrome eating disorders affect around 10% of adolescent girls. Given the
seriousness of the consequences of eating disorders, and the large number of Australians affected, a better
understanding of what causes the development of eating disorders is required. The current research investigates
identical and non-identical adolescent female twins aged 13-15 years. As well as examining their eating, this study
will look at the sort of environments and temperaments that may increase genetic susceptibility to develop eating
problems. The types of environment to be examined include media influence, weight related peer teasing, parental
dieting, and pre- and pernatal complications. Twin temperament will also be examined, including perfectionism,
sense of ineffectiveness, body dissatisfaction and depression. Parental anxiety and novelty seeking will also be
examined for impact on the development of disordered eating in their children. The twins will be followed up over
a 2-year period, the peak risk age for onset of eating problems. By comparing the identical and non-identical
twins, we can define the characteristics of those most at risk of developing eating problems. The results of this
project can be used to formulate specific prevention strategies.
Research achievements (from final report):
The original aim was to assess 400 families, where parents completed a self-report questionnaire and their twin
daughters completed an interview over the telephone. At Wave 1, of the 411 families approached, parents from
350 families (85.4%) returned self-report questionnaires, and 699 twins were interviewed. At Wave 2, 351
families were followed up, and 668 twins were interviewed. Both waves of data collection are complete. A
subsequent grant from NHMRC (480420) is now being used to conduct a third wave of data on this cohort
including genotyping and neuropsychological functioning. The potential benefits of this valuable data set are
multiple as it represents: (1) A prospective longitudinal data set that can inform our understanding of risk factors
for disordered eating, (2) data that can be used to inform revision of DSM-V with respect to better recognition of
the EDNOS cateogry, (3) data that will identify potential endophneotypes for disordered eating that will aid in the
search for candidate genes, and (4) a unique data set of twins that allows for investigation of GxE in increasing the
risk of disordered eating.
Expected future outcomes:
The data set is unique in the world as being the only longitudinal and prospective data set of adolescent twins,
who ar enow becoming adults. As such, future publications will capture much attention. Its value has already been
noted as its work was selected for focus in a BBC documentary being made in 2009 - our work in eating disorders
was chosen above other twin registries in the world.
Name of contact:
Email of contact:
Tracey Wade
tracey.wade@flinders.edu.au
NHMRC Research Achievements - SUMMARY
Garvan Institute of Medical Research
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
7028
Dr Ian P Blair
Genetics not elsewhere classified
Garvan Institute of Medical Research
Start Year:
End Year:
Total funding:
Grant Type:
2000
2004
$55,000.00
Peter Doherty Fellowship
Title of research award: Australian Postoctoral Fellowship (Peter Doherty). Title: Positional cloning of a
susceptibility gene on chromosome 4q35 for bipolar affective disorder.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Bipolar disorder is a major psychiatric illness with a population prevalence of up to 1.6%. The disorder is
genetically complex and its biological basis remains unknown. Genetic linkage analysis was used to localise a
gene that confers susceptibilty to bipolar disorder on chromosome 4q35. Positional cloning was combined with
association analysis to provide evidence that a cadherin gene, FAT, confers susceptibility to bipolar disorder in
four independent patient cohorts (allelic P values range from 0.003 to 0.024). The bipolar associated region of the
FAT gene was localised to an interval that encodes an intracellular EVH1 domain of the FAT protein. This
domain interacts with Ena/VASP proteins, as well as beta-catenin binding sites. Expression of Fat, Catnb (betacatenin), and the three genes (Enah, Evl, and Vasp) that code for the Ena/VASP proteins, were investigated in
mouse therapeutic treatment models of bipolar disorder. Fat was shown to be significantly downregulated
(P=0.027), and Catnb and Enah were significantly upregulated (P=0.0003 and 0.005 respectively), in response to
therapeutic doses of the anti-manic drug, lithium. Using a protein interaction map, the expression of genes
encoding mouse homologues of the FAT (ft) interacting proteins was investigated. Of 14 interacting molecules
that showed expression following microarray analysis, eight showed significantly altered expression in response to
therapeutic doses of lithium (binomial P=0.004). Together, these observations implicate FAT and it's protein
partners in a molecular pathway involved in the pathogenesis of bipolar disorder. This identifies potential targets
for novel therapeutic treatments for those who suffer from this devastating illness.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
Ian Blair
i.blair@garvan.org.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
230802
Prof Peter R Schofield
Psychiatry
Garvan Institute of Medical Research
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$780,000.00
Standard Project Grant
Title of research award: Understanding the molecular basis of bipolar affective disorder
Lay Description (from application):
Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1.6%.
The illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion
to normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be
the sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide
fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary
prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown.
However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an
opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to
investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously
reported strong evidence for a novel bipolar disorder susceptibility gene on chromosome 4, a finding which has
subsequently been reproduced in several independent studies. Consequently, we hypothesise that there is a gene
located on chromosome 4 that predisposes to bipolar disorder. The aim of this proposal is to identify the
chromosome 4 bipolar susceptibility gene and understand how the gene causes bipolar disorder. Identifying the
genes responsible for bipolar disorder will allow us to define and understand the biological basis of this severe
psychiatric condition. This will ultimately lead to major improvements in the ability to diagnose, treat and prevent
the illness.
Research achievements (from final report):
This project has identified and characterised a susceptibility gene located on chromosome 4q35 that predisposes to
bipolar affective disorder. It has: 1. identified, mapped, and characterised all genes within the bipolar disorder
candidate region on chromosome 4q35. 2. screened all genes within the candidate region for sequence variations
using bipolar kindreds that show evidence for linkage to the chromosome 4q35 locus. 3. tested these sequence
variations in a large bipolar case-control cohort, in order to identify the gene that shows a positive association with
the disorder, which was shown to be the protocadherin gene FAT. 4. validated the role of the protocadherin FAT
susceptibility gene in large independent bipolar cohorts. 5. studied the expression and function of the FAT bipolar
susceptibility gene and begun to investigate the functional consequence of the sequence variations in illness
predisposition and defined the molecular and biochemical pathways involved in the pathogenesis of the disorder.
Expected future outcomes:
Identification of the specific molecular mechanisms by which the FAT gene results in susceptibility to bipolar
disorder
Name of contact:
Email of contact:
Prof Peter R Schofield
p.schofield@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Griffith University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
145308
Prof Paula M Barrett
Mental Health
Griffith University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$351,634.00
Standard Project Grant
Title of research award: Project Grant
Lay Description (from application):
Anxiety and depression are the most common forms of psychological distress affecting Australian children today.
These disorders are seriously disabling and continuous across time. Therefore, it is very important to understand
more about the onset and course of these disorders, and about factors which influence these disorders in either a
positive or negative manner. There are three major goals for the current project. The first is to further our
understanding of the development, maintenance, and amelioration of anxiety and depression in a child and youth
population. The second is to understand the relationship between these two disorders in children and youth. The
third is to use the acquired information to assist in the identification of optimal ages for preventive interventions,
and to aid in the matching of interventions to the specific needs and vulnerabilities of children versus adolescents.
This project aims to meet these goals through implementation of a controlled prevention trial. The aims fo the
research are: 1. To examine the relationship between symptoms of anxiety and depresison in Australian children
and youth 2. To gain valuable clinical information regarding the assessment and prevention of these disorders 3.
To understand the risk and protective factors associated with these disorders, and the impact of these factors over
time 4. To implement and evaluate a school-based prevention program The expected outcomes of the research are:
1. To acquire valuable information related to the onset & course of anxiety and depression in children and youth,
and their associated risk and protective factors 2. To further development of more timely and targeted
interventions for the prevention of anxiety and depression 4. To enhance the emotional resilience of participating
children and prevent the onset of anxiety and depression 5. To promote Australian research by publishing the
results of the project within the international research literature
Research achievements (from final report):
This project represented the first controlled trial of universal prevntion for both child anxiety and depression;
presenting longitudinal results up to three-years follow-up. This project has identified optimal timing of
intervention for prevention of emotional distress in schools; with results indicating strongest preventative effects
for primary school-aged children. These results provide evidence that prevention of anxiety and depression must
start early in school, and continue throughout schooling in a multi-level approach to provide durable preventative
effects. This poroject was significant in terms of altering the trajectory of risk for child and youth with emotional
distress. Results provided evidence that risk for anxiety and depression was reduced over time, reducing the onset
of anxiety and depressive disorders in schools where children and youth received an evidence-based prevention
program compared to schools which did not receive such intervention. .
Expected future outcomes:
This project has the potential to produce long-term effective prevention outcomes for a large sample of children
and youth. The intervention delivered in this project may provide longer term outcomes, with a reduction in actual
adult psychopathology, and associated reductions in economic loss and personnal suffering associated with adult
mental health.
Name of contact:
Email of contact:
Paula Barrett
P.Barrett@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
189405
Prof Alan Mackay-Sim
Psychiatry
Griffith University
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$355,000.00
Standard Project Grant
Title of research award: Schizophrenia, vitamin D and brain development
Lay Description (from application):
Schizophrenia is a group of brain disorders that affects approximately 1 in 100 people. The symptoms can include
delusions (false beliefs), hallucinations (e.g., hearing voices), blunted emotions, poor planning ability and reduced
motivation. Because these disorders often start in early adulthood, and can be chronic, schizophrenia contributes
substantially to the burden of disease across the globe. The causes of schizophrenia are poorly understood, but it is
clear that both genetic factors and environmental factors can contribute to the risk of developing schizophrenia. As
part of an integrated program of research searching for novel environmental risk factors for schizophrenia, this
application examines the impact of low prenatal vitamin D on brain development. Vitamin D is a steroid hormone
mostly derived from the action of bright sunshine on the skin. Our past research (based on population studies, cell
culture studies and animal experiments) have provided tantalizing clues about the impact of low prenatal vitamin
D on brain development. This project will explore two important areas. We will explore mechanims by which
LOW vitamin D may cause LESS programmed cell death (apoptosis). Programmed cell death is a crucial feature
in brain development, and any alteration to the orderly sequence of brain development may leave the person
vulnerable to adult-onset brain disorders like schizophrenia. Secondly, we will compare the behaviour and brain
markers of adult rats born of mothers depleted of vitamin D versus normal mothers. Finally, we will examine the
impact of vitamin D on neural tissue cultures obtained from nasal biopsy. If low prenatal vitamin D is a risk factor
for schizophrenia, then it may be possible to reduce the incidence of schizophrenia by providing pregnant women
with a safe and cheap vitamin tablet (similar to how folate supplements have reduced the incidence of spina
bifida) .
Research achievements (from final report):
Studies show that a significant number of women of child bearing age are deficient in vitamin D, even in Australia
and even in sunny Queensland. The main source of vitamin D is from the action of sunlight on the skin. Low
sunshine levels during early development are associated with increased risk in schizophrenia. Our research is
demonstrating that vitamin D is important in brain development. We have found that the vitamin D receptor is
found throughout the human human brain. In rats, we found that low vitamin D during embryonic development
changes the size and shape of the brain at birth. This was accompanied by cellular changes in the brain and
changes in the chemical composition in the brain. When these animals became adults subtle changes in brain
shape and chemistry remained. There were also subtle, though significant, changes in adult behaviour. These
animals were significantly more active. The interesting aspect of this increased locomotion is that it appears to
result from increased dopamine in the brains of these animals deprived of vitamin D during development.
Increased dopamine is characteristic of schizophrenia and the main drugs used to treat schizophrenia cause a
decrease in the action of dopamine. We are currently testing this hypothesis by direct measurement of dopamine in
the brains of these animals. Vitamin D is likely to be important for human brain development; deficiency may lead
to changes in adult brain and behaviour, and may increase the risk of some diseases.
Expected future outcomes:
The goal of our research is to ascertain the importance of vitamin D in brain development and its effects on the
adult brain. This may help understand how low vitamin D during development increases the risk of schizophrenia.
If so, vitamin D supplementation in pregnancy may reduce this risk.
Name of contact:
Email of contact:
Professor John Mcgrath
john_mcgrath@qcmhr.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
326220
Start Year:
2005
CIA Name: Dr Sharon Dawe
End Year:
2008
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$0.00
Admin Inst: Griffith University
Grant Type: Standard Project Grant
Title of research award: An empirical investigation of psychosis proneness in amphetamine users: Current and
predictive validity
Lay Description (from application):
The use of amphetamines has increased in Australia in the last decade. According to the 1998 National Household
Survey, lifetime use of amphetamines has increased by over 50% from approximately 6% in 1995 to
approximately 9% in 1998; recent use (last 12 months) has increased from 2% in 1995 to approximately 4% in
1998. This increase appears to be even greater in Queensland, the site of the proposed study, which has seen both
an overall increase in the use of illicit drugs and an increase in the use of amphetamines specifically. The most
recent estimate of the number of current users (use within the last 12months) aged 14 years and over in
Queensland is 85.5000. This compares to 17.000 recent heroin users in the same age range. Of particular concern
is the increase in the use of methamphetamine, which has high abuse potential producing euphoric effects that are
similar to, but longer lasting than, those of cocaine. Also of concern, given the increasing purity and availablity of
methamphetamine, is the link between amphetamine use and psychosis, a psychotic disorder characterised by
sensory hallucinations, paranoid delusions and a loosening of associations. Despite this well established link, there
are surprisingly few studies in which the course and onset of amphetamine psychosis has been studied. In this
reseach the relationship between subclinical features of psychosis, measures of psychosis proneness and other
factors implicated in the development of schizophrenia will be investigated in a prospective cohort in which
amphetamine users will be followed up once per month for twelve months.
Research achievements (from final report):
This study investigated the relationship between dose, pattern and duration of use amphetamine use and emergent
psychotic symptoms in a cohort of amphetemine users. Of particular interest was determining the relative
contribution of dose, family history of schizophrenia. The final sample consisted of 201 amphetamine users who
were contacted monthly for 12 months to ask about their substance use and general emotional health including
symptoms associated with psychosis such as suspiciousness and hallucinations. Rention was good with
approximately 86% of the sample retained. Preliminary data analyses point to high rates of psychosis and ongoing
drug use.
Expected future outcomes:
This study will pave the way for further investigations into psychosis proness in amphetamine users. The high
rates of psychosis and the high rates of subclinical sympotms in partiucalr hostilitya nd suspiciousness add to the
clinical literature and indicate that services need to consider these as tyical consequences of amphetamine use.
Name of contact:
Email of contact:
Professor Sharon Dawe
s.dawe@griffith.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
326231
Prof Kim Halford
Health, Clinical and Counselling Psychology
Griffith University
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$0.00
Standard Project Grant
Title of research award: A randomized controlled trial of a couple-based program for the transition to
parenthood.
Lay Description (from application):
Couples who become parents face a very important and potentially very rewarding task: working together to raise
their child. The current research evaluates the effects of a couple-based education program for people having their
first child. The program helps couples develop realistic expectations about parenthood and effective ways of
supporting each other as parents. The program also helps partners to understand and promote positive infant
development, to enhance their couple communication, and to promote a positive couple relationship while
parenting. The program is offered through one face-to-face workshop held during the late stage of pregnancy, and
then a home-based learning package consisting of a mix of videotaped information packages, reading and
telephone based sessions with a psychologist. The overall aim is to produce an easily accessible support program
for new parents that will enhance a couple's relationship with each other and their child. It is hoped this will
reduce problems and enhance enjoyment of people becoming parents.
Research achievements (from final report):
Two approachs to assisting and supporting couples having their first child were compared: Becoming a Parent - an
individual education program for the woman focused on support and infant care, and Couple CARE for Parents
(CCP) - a couple focussed program helping the partners to support each other, parent effectively, and enhance
their couple relationship. Relative to couples doing the individual program, couples completeing CCP
significantly improved their couple communciation, and reported higher relationship satisfaction and less
parenting stress and these benefits were maintained two years after the birth. The couple support and education
program was of particular help to couples that had a baby that was difficult to soothe, couples that lacked social
support from family, or that had low relationship satisfaction before the birth.
Expected future outcomes:
The CCP couple program is being trialed in the United States and tested for its ability to help single, low income
couples, and whether the porgram reduces the prevalence of inter-partner violence within couples.It is hoped that
the porgram will become widely available to expectant parents.
Name of contact:
Email of contact:
Kim Halford
K.Halford@psy.uq.edu.au
NHMRC Research Achievements - SUMMARY
James Cook University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
252741
A/Pr Komla Tsey
Indigenous Health
James Cook University
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$464,850.00
Standard Project Grant
Title of research award: Evaluation of Family Wellbeing (FWB) Empowerment program: a participatory action
research initiative
Lay Description (from application):
We have shown that family well being empowerment training in Indigenous communities can significantly
enhance program participants' sense of control and responsibility for the conditions affecting their health and well
being (Tsey and Every, 2000a;Tsey and Every, 2000b). Following this, there has been a great deal of interest and
demand for the family well being program not only in Indigenous Australia, but also among Maori people in New
Zealand. Presently, we are involved in four collaborative initiatives with indigenous communities in response to
growing interest and demand for the program. The current proposal is a joint initiative between University of
Queensland, Apunipima Cape York Health Council and Gurriny Yealamucka Health Services which aims to: a.
Consolidate and extend the existing family well being initiatives in Hopevale and Yarrabah to two other north
Queensland communities (yet to be selected from several that have expressed an interest), using a participatory
action research process b. Undertake a meta evaluation of outcomes across all four sites This proposal aims to
increase our understanding about ways in which individuals and groups of people can be better supported in their
efforts to bring about changes in personal and social life.
Research achievements (from final report):
Empowerment is a process whereby individuals and communities of people become stronger and more confident
in controlling or exerting greater influence over the issues affecting their lives. It is a two-way process. Individuals
need to learn to take greater responsibility and control for their own situation or processes of change. But for
individual change to be effective and sustainable, reciprocal change needs to occur in the wider social
environment. The values based Family Wellbeing (FWB) empowerment tool has proved highly relevant to the
challenge of rebuilding social norms in Indigenous communities. Self-reported improvements in FWB participant
Social and Emotional Well-Being included those occurring at the level of the individual and those which radiated
further, translating into positive effects on relationships within the family and the broader community. Individual
changes included recognition of one's potential in relation to further education, capacity to improve current living
conditions, such as creating a peaceful home, reading more, beginning the process of healing trauma related to
sexual abuse, improved confidence, trust , empathy and 'having the courage to say "No"' Changes within the
family included spending more time at home, building confidence between husband, wife and children, talking to
children 'properly', 'coming down to your children's level' and doing activities with the family, such as going
fishing or taking children to the beach. A wide range of health, education and other human services are now
incorporating the empowerment tool into their activities.
Expected future outcomes:
Consolidation and adaptation of the approach to the needs of 4 new communities as part of a $1.5 National
Suicide Strategy funding suicide prevention project (2007-9); development of quantitative tools to measure
outcomes including economic evaluation of future empowerment interventions, thereby strengthening the
evidence base in the important but little researched area of empowerment and health.
Name of contact:
Email of contact:
Komla Tsey
komla.tsey@jcu.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
333414
Dr Alan R Clough
Mental Health
James Cook University
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2005
2008
$300,000.00
Public Health (Australia)
Title of research award: Improving the evidence base to reduce harm from alcohol and other substance use in
northern Australia and surrounding regions: developing a centre of excellence.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The principal aim of this research was to compile data on substance use and related health indicators in rural and
remote localities in northern Australia. I used a 'community epidemiology' approach to compile data on substance
use patterns and consequences, particularly tobacco, cannabis and alcohol. A significant evidence base has been
developed to guide the development of harm reduction strategies and policies, to build the capacity of local
community people to become involved in collecting their own evidence for sustained intervention strategies. The
local cultural relevance, validity and reliability of evaluations of initiatives has been enhanced. A team of
researchers conducting prevention studies has been developed in north Queensland.
Expected future outcomes:
Strategies to address cannabis and tobacco problems will be enhanced across far north Queensland. Alcoholrelated violence in inner-city areas will be reduced.
Name of contact:
Email of contact:
Rick Speare
rick.speare@jcu.edu.au
NHMRC Research Achievements - SUMMARY
La Trobe University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
107224
Prof Alan Shiell
Health Economics
La Trobe University
Start Year:
End Year:
Total funding:
Grant Type:
2000
2002
$505,000.00
Standard Project Grant
Title of research award: Economic evaluation of PRISM: a community based intervention trial
Lay Description (from application):
This project evaluates the costs and outcomes of PRISM (Program of Resources, Information and Support to
Mothers). PRISM is a community based intervention designed to promote the physical and mental health of
mothers. This research project seeks to evaluate the costs and outcomes of the PRISM intervention in order to help
inform judgements about its value. PRISM is being introduced in 8 local communities in Victoria with a further 8
communities acting as comparators. The full costs of the intervention will be measured as will the impact the
intervention has on the physical and mental health of mothers. Estimates of the intervention's economic benefits,
that is the value that community members attach to the intervention's main outcomes will also be ascertained. In
this way it is possible to judge whether or not the benefits of PRISM are worth its costs. Advanced statistical
techniques will be used to ascertain the extent to which improved health outcomes in mothers are determined by
individual, organisational or community-level factors.
Research achievements (from final report):
This project (EcoPRISM) added an economic and ecological evaluation to a sister project (also funded by
NHMRC) called PRISM. PRISM was a community-based, cluster randomised trial to evaluate an intervention to
promote the health of recent mothers. The EcoPRISM project used innovative methods for recording
prospectively how the intervention unfolded in each of the intervention communities,. In addition, we evaluated
the broader impact of the intervention (on council policies for example) and the cost-effectiveness of the
intervention. The contribution that EcoPRISM will make falls into two areas - methods development in complex
interventions and policy evaluation. The lessons learnt in this project will enable us improve the design and better
evaluate the implementation of complex interventions in communities and organisations.
Expected future outcomes:
The project has provided the foundation for a six year, $2.4 million international collaboration on theory, methods
and ethics of complex interventions that links Australian researchers with Canada, the UK, and the USA, funded
by the Canadian Institutes of Health Research
Name of contact:
Email of contact:
Alan Shiell
ashiell@ucalgary.ca
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
191215
Prof Judith Lumley
Epidemiology
La Trobe University
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$252,500.00
Standard Project Grant
Title of research award: Reducing maternal depression two years after birth: follow-up cohort within a
community randomised trial
Lay Description (from application):
Maternal depression following childbirth is a significant public health issue. Previous Victorian research has
found that 15-17% of women experience depression 6-9 months after birth, and of those depressed then, 30% are
likely still to be depressed or depressed again two years after the birth. In 1998 16 Victorian municipalities began
participating in the first ever community randomised trial of prevention and early intervention in depression PRISM (Program of Resources, Information and Support for Mothers). PRISM involves eight areas participating
in a range of primary care and community based strategies designed to mobilise appropriate community support
for mothers and children with a view to reducing maternal depression and improving maternal physical health and
recovery after birth. The other eight areas are participating as comparison communities. Evaluation in PRISM is
assessing major health outcomes for mothers and wider community benefits (flow-on effects) of the intervention
program. Process and impact evaluation has also been undertaken to document and assess the different program
elements and enhance the reproducibility of the program if successful. All women giving birth in the 16 areas are
currently being surveyed six months after birth (from August 2000-February 2002). Within PRISM it is now
proposed to follow-up women again two years after birth, to assess the impact of the intervention program on:
*recovery from depression among the group of mothers in both intervention and comparison areas who were
depressed six months after birth; and *the overall prevalence of depression and physical ill-health in all mothers.
This follow-up study has the capacity to provide infromation on the poorly documented natural history of maternal
depression from birth through the next two years in a large sample, including both urban and rural residents.
Research achievements (from final report):
This project completed the research undertaken for a large community intervention study PRISM (Program of
Resources, Information and Support for Mothers) which investigated a range of primary care and commuity-based
strategies toreduce maternal depression and improve maternal physical health after childbirth. Details of the main
PRISM study and its findings are available on the project website: www.latrobe.edu.au/mchr/prism This project
enabled follow-up of women to two years after birth, and over 9,000 women from sixteen municipalities (eight
metropolitan and eight rural) returned questionnaires mailed to them on behalf of the research team by their local
council. The study will report findings concerning the impact of the PRISM intervention strategies on maternal
health outcomes to two years post-birth. These include recovery from depression in the group of women who were
depressed at six months after birth in both intervention and comparison communities, and the overall prevalence
of depression and physical ill-health in all mothers. It is expected that findings from the study will be available in
2009.
Expected future outcomes:
The outcomes of the study will provide information on the poorly documented natural history of maternal
depression from birth through to two years in a large sample including both urban and rural residents
Name of contact:
Email of contact:
Prof Judith Lumley
j.lumley@latrobe.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
280617
Dr Angela J Taft
Primary Health Care
La Trobe University
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$423,500.00
Standard Project Grant
Title of research award: MOSAIC (MOtherS' Advocates In the Community) randomised controlled intervention
trial
Lay Description (from application):
Intimate partner abuse or domestic violence is common and damaging for women in the early childbearing years.
It has a negative effect on the mental and physical health of women and their children. Because of poor health,
victimised women and children are frequent attenders to family doctors (GPs), but doctors face many barriers in
making an effective response. One of these barriers is the critical absence of evidence for what would help women
attending GPs in dealing with partner abuse. This is vital to inform both GP training and clinical practice. There is
sound evidence that home visiting or support by peers improves the health of disadvantaged mothers and children.
Similarly, advocacy improves the health and wellbeing of abused women. The MOSAIC community intervention
trial combines these two elements: home visiting/peer support and domestic violence advocacy and this strategy
will be evaluated in a randomised trial. The trial aims to reduce partner abuse and depression among women
pregnant or with children under 5 attending GPs. It also aims to strengthen mother-child bonds. Trained and
supported GPs from 40 participating practices will identify 700 abused or at risk women over a 40 week period.
Women in the intervention arm of the trial, identified as abused or at risk by their GPs will be offered the support
of trained para-professional 'mentor mothers' for up to a year, while the comparison arm will be offered standard
GP care. Recent funding allows a pilot study of mentor mother recruitment and training to be undertaken in 2003.
The study will strengthen GP support for this difficult issue and build a 'critical mass' of GPs interested in partner
abuse management in the 5 participating divisions. The MOSAIC study will assess the value to GPs and women
of an enhanced support system for victims' care and provide much needed evidence of an intervention embedded
in general practice to reduce partner abuse of pregnant women and women with young children.
Research achievements (from final report):
MOSAIC successfully evaluated a social support strategy - community mentor mothers - to improve the safety,
mental wellbeing and parenting strength of recent mothers experiencing intimate partner violence (IPV) - with a
rigorous trial design and a sub-study in the Vietnamese community. The results (when published) will have
significance for the care of all maternal victims enduring IPV. The study developed acknowledged new resources
for primary care clinicians seeing women experiencing IPV. 1. An innovative curriculum and international
consensus guidelines for general practioners (GPs) to work with victims, perpetrators and children experiencing
IPV. The guidelines have been endorsed and disseminated by the RACGP on their website and referred to in the
RACGP Red Book on Preventive Medicine (RACGP). 2. A new study involving the eight maternal and child
health (MCH) nurse teams involved in MOSAIC was funded by the ARC to further develop and evaluate an
evidence-based good practice model for MCH nurses caring for new mothers experiencing partner violence.
MOSAIC has published a mentor training manual and study protocol and undertaken (a) process and impact
evaluation surveys with over 160 clinician stakeholders and (b) in depth inteviews with 36 participant women and
18 mentors (including those speaking Vietnamese, conducted in their own language). This enhances the
sustainability of the study and responds to calls for more comprehensive methods for complex intervention trials.
MOSAIC has been presented to six international conferences and results will be presented to the US government
multidisciplinary Family Violence Prevention Fund and WONCAEurope (family medicine) conferences in late
2009.
Expected future outcomes:
Mentor mothers are a potential strategy for Australian policy-makers to complement formal family/domestic
violence services in order to prevent and reduce partner violence among mothers who are enduring these harmful
behaviours, even in CALD communities. Australian primary care clinicians will be better trained, resourced and
supported to care for their patients/clients experiencing IPV.
Name of contact:
Email of contact:
Dr Angela Taft
a.taft@latrobe.edu.au
NHMRC Research Achievements - SUMMARY
Macquarie University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
192107
Prof Ronald M Rapee
Health, Clinical and Counselling Psychology
Macquarie University
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$302,500.00
Standard Project Grant
Title of research award: Theoretically guided improvement in the treatment of social phobia: A randomised
controlled trial. (2002-2004)
Lay Description (from application):
Social phobia is a serious mental disorder that affects up to 13% of the population across their lifetime and causes
marked life interference and costs to the community. Treatments for social phobia have been improving over the
past decades and currently, there is good outcome with standard treatment packages. However, several authors
have pointed out that treatment outcomes, while good, are far from perfect. We have recently developed a model
of social anxiety that points out how people with social phobia may be different to the average. Based on this
model, we can make several predictions for potential improvements to current treatment packages. The current
grant seeks to test these improvements. The proposal is to compare people with social phobia who receive a
standard treatment package with those who receive this packaged plus the newly predicted components. It is
predicted that the addition of these extra components will results in considerably greater improvements in both the
short and long terms.
Research achievements (from final report):
Social anxiety can be a debilitating condition when experienced at severe levels and can dramatically interfere
with a person's life. Non medication treatments over the past 30 years have shown some good promise and have
resulted in reasonable changes that last for many years. However, effects are limited and there is always hope for
greater efficacy. The past five years have seen improvements in our understanding of some of the mechanisms that
maintain this condition. In turn, this has lead to gradual changes in the strategies used to treat social anxiety.
While it is hoped that these changes have resulted in stronger effects of treatment, at this stage, we do not know
whether this is the case. The current study was aimed to answer this question. One hundred and fifty people with
high levels of social anxiety were given one of three possible treatments: general relaxation and stress
management, a traditional psychological (cognitive behavioural) treatment program, or a "newer" cognitive
behavioural treatment program in which the traditional strategies were enhanced with new techniques based on
current models. While we have not yet analysed all of the results, preliminary indications are that the new
treatment package is proving significantly better than either the nonspecific stress management package or (more
importantly) the traditional package. These results mean that we can be confident that we are moving in the right
direction with newer, non-medication treatments for social anxiety. Importantly, we now have treatments that are
even more effective for reducing the burden of this serious mental disorder and for helping people to achieve a
satisfying and fulfilling life.
Expected future outcomes:
As a result of this research we are now able to identify some of the most effective treatments for the reduction of
social anxiety. It is expected that the effects of this treatment will last and they do not rely on the use of
medications. These results will allow hundreds of thousands of Australians to increase their life satisfaction and
the roles that they play in our society.
Name of contact:
Email of contact:
Prof Ronald Rapee
Ron.Rapee@mq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
235307
Dr Charles D Blaha
Central Nervous System
Macquarie University
Start Year:
End Year:
Total funding:
Grant Type:
2003
2004
$230,000.00
Standard Project Grant
Title of research award: Neuropathways and synaptic adaptations underlying drug addiction in central dopamine
systems
Lay Description (from application):
There is a rising trend in addiction to drugs, such as opioids (heroin) and stimulants (methamphetamine and
ecstasy). A key feature of this addiction is intensified craving for the drug with repeated use. A major brain
component thought to mediate drug-craving is the dopamine (DA) neurotransmitter system, consisting of cells in
the midbrain that project nerve terminals to forebrain structures involved in reward-based learning. DA cells
undergo long-term depression (LTD) and potentiation (LTP) of synaptic strength when excitatory inputs to DA
cells are stimulated. These findings are important to drug addiction as amphetamine has been shown to block LTD
and enhance LTP in brain slices of DA cells. Thus, changes in LTD and LTP by illicit drugs may underlie the
conditions necessary for expression of drug-induced behavioural sensitisation, the best-accepted model of drugcraving in human addiction. To date, these studies have all been conducted in brain slices. Therefore, the
functional importance of this synaptic plasticity in midbrain DA cells has yet to be shown in terms of changes in
DA release in forebrain terminals in the living animal. For the first time we will address this issue by recording
DA cell firing activity together with DA release using a newly developed technique that permits DA release to be
monitored in the living brain in 'real-time' (100,000 samples/sec). This will allow us to identify the origin (cortical
excitatory inputs) and receptor mechanisms that mediate LTP and LTD in DA cells and their effects on DA
release.Recording DA cell activity with real-time measurement of DA release will promote a new cutting-edge
technology to the Australian Neurosciences. These data will provide 'first of its kind' evidence of the functional
anatomy and receptor mechanisms underlying synaptic plasticity in DA neurons associated with repeated drug use
and ultimately enhance our basic understanding of the neural mechanisms of human drug addiction.
Research achievements (from final report):
There is a rising trend in Australian youth to abuse illicit drugs that are highly addictive, such as
methamphetamine and ecstasy. A key feature of addiction to these drugs is intensified craving with their repeated
use. A brain component implicated in mediating drug craving is the dopamine neurotransmitter system with
neuronal cells residing in the human midbrain and projecting to several forebrain structures. The release of
dopamine in these forebrain structures strengthens the perception of the pleasurable effects of these drugs. As
such, an increase in release of dopamine in the forebrain by drugs of abuse is considered an essential physiological
'first-step" to drug addiction. Recordings in brain slices indicate that dopamine cells undergo normal expected
changes in synaptic strength (plasticity) when excitatory neuronal inputs to dopamine cells are active. However,
exposure to drugs of abuse appears to enhance this synaptic plasticity. The present research combined
electrophysiological and neurochemical recording techniques to quantify the impact of amphetamines on midbrain
dopamine neuron firing activity and forebrain dopamine release. This cutting-edge technology allowed the
identification of both the origin of excitatory inputs to dopamine neuronal cells, as well as the receptor
mechanisms in the midbrain that mediate the marked changes in dopamine cell synaptic activity and the
consequences of these changes on dopamine transmission in the forebrain. These findings are important to
understanding drug addiction as they provide clues as to what may underlie the physiological conditions necessary
for the expression of drug addiction in humans.
Expected future outcomes:
Results obtained from our studies of the functional anatomy and receptor mechanisms underlying normal and
amphetamine-modified dopamine synaptic plasticity will enable identification and further analysis of critically
important maladaptive neural mechanisms associated with acute and repeated exposure to other drugs of abuse,
such as heroin and alcohol.
Name of contact:
Email of contact:
Charles D. Blaha
cblaha@memphis.edu
NHMRC Research Achievements - SUMMARY
Grant ID:
192111
Start Year:
2002
CIA Name: Dr Melissa J Green
End Year:
2006
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$219,024.00
Admin Inst: Macquarie University
Grant Type: Australian Clinical Research
Fellowship
Title of research award: Perceiving and believing: Forming beliefs about others intentions from facial
expressions in their social context.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
In a series of experiments combining cognitive and psychophysiological (eye-movement) data, this research
showed that cognitive deficits in attention and context processing in schizophrena contribute to impaired mental
state perception in others, from faces expressing different emotions within naturalistic social settings. The research
was the first to examine context processing deficits in schizophrenia with reference to social cognition, and
received additional financial support from Macquarie University, the Schizophrenia Research Institute (SRI)
Australia, and the National Alliance for Research on Schizophrenia and Depression (NARSAD), USA. The
research led to national collaboration with researchers at the Universities of Melbourne, Sydney, and New South
Wales, as well as ongoing international collaborations with the Universities of London, Texas, and the Max
Planck Institute, Germany. These collaborations have seen the adaptation of social context processing tasks for
use with native American samples, other clinical populations (e.g., bipolar disorder, borderline personality
disorder), neuroimaging technologies, and more recently, the remediation of social-cognitive deficits in
schizophrenia. To date, research activities within the Fellowship period have resulted in the publication of two
book chapters, ten journal publications, and 15 conference papers. Ongoing research at Macquarie University
follows from initial success in showing short-term remediation of facial emotion processing impairments in
schizophrenia, using an interactive training tool that teaches the participant to redirect visual attention to relevant
features of social information. Future research to determine the long term benefits of this remediation package,
and/or the development of new tools targeting both social cognitive and related neurocognitive skills, has the
potential to significantly impact on standard clinical treatment of cognitive and social difficulties in schizophrenia.
Expected future outcomes:
The continued development of user-friendly, interactive remediation tools to target social and emotion processing
difficulties, alongside core cognitive deficits in psychosis, will lead to increased accessibility of treatment options
that can augment pharmacological management of symptoms, and ultimately facilitate long term improvements in
cognitive and social functioning in psychotic disorders.
Name of contact:
Email of contact:
Dr Melissa Green
melissa.green@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
281514
Dr Carolyn A Schniering
Health, Clinical and Counselling Psychology
Macquarie University
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$269,625.00
New Investigator
Title of research award: Improved treatment of comorbid anxiety and depression in adolescents: A randomised
controlled trial
Lay Description (from application):
Anxiety and depression are serious mental disorders that affect large numbers of children and adolescents in our
community. In particular, young people with both anxiety and depression may experience severe difficulties
including poor physical health, social and interpersonal problems, academic problems, drug and alcohol problems,
long-term adjustment problems and suicidal behaviour. Although a range of very effective treatments have been
developed to treat anxiety and depression separately, there is very little work on the treatment of young people
with both these problems. Some studies suggest that youth with both anxiety and depression together do worse in
currently available treatments, compared to their peers with only a single condition. The current grant seeks to test
whether a new treatment addressing both anxiety and depression concurrently, is superior to standard treatments
for adolescents experiencing both these emotional problems. It is predicted that the addition of extra components
to standard treatments, will result in considerably greater improvements in these more complex cases.
Research achievements (from final report):
Adolescents with concurrent anxiety and depression experience severe difficulties including poor health,
interpersonal problems, academic problems, drug/alcohol problems, and suicidal behaviour. Although effective
treatments have been developed to treat anxiety and depression separately, there are few treatments for young
people with concurrent problems. Studies show that adolescents with both difficulties do not do as well as their
peers with a single problem, using available treatments. This innovative study tested a new targeted treatment for
adolescents with comorbid anxiety and depression. The study was conducted at the Centre for Emotional Health,
Macquarie University. The new treatment integrated cognitive-behavioural components for anxiety and depression
into one intensive package, and included components for parents on how to support their child. Adolescents were
randomly allocated to either the new treatment or a wait-list condition. Results showed that the severity of anxiety
and mood disorders decreased significantly at post, and a significant proportion of adolescents were diagnosis free
compared to waitlist. Importantly, life interference related to emotional problems was also reduced and levels of
positive emotion increased. These gains were maintained at 6 and 12-month follow-up. The new programme looks
to be promising in the treatment of comorbid anxiety and depression in youth. The programme and its related
treatment manuals (adolescent, parent, therapist) will have applications in many mental health settings nationally
and internationally. Effective treatments for childhood disorders are essential to early intervention, and also the
prevention of mental health problems into adulthood.
Expected future outcomes:
This project was the first step in developing more targeted treatments for youth with comorbid anxiety/depression.
Effective treatments are essential to early intervention and prevention of mental health problems into adulthood.
The next step may be to improve on cost effectiveness by reducing the number of sessions.
Name of contact:
Email of contact:
Dr Carolyn Schniering
carolyn.schniering@mq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
382008
Dr Jennifer L Hudson
Health, Clinical and Counselling Psychology
Macquarie University
Start Year:
End Year:
Total funding:
Grant Type:
2006
2009
$371,575.00
Standard Project Grant
Title of research award: Enhancing the efficacy of cognitive behavioural treatment for children with anxiety
disorders: Treating parent anxiety
Lay Description (from application):
Much attention is focused on childhood problems such as attention-deficit, depression and substance abuse.
However, the most prevalent psychological problem experienced in childhood is anxiety. There is even some
evidence to suggest that anxiety may lead to later problems such as depression or substance abuse. We know that
anxiety disorders are a widespread problem in our youth. We also know that anxiety, if left untreated, will persist
through the child's life and cause significant disruption to their life. The good news is that there has been an
increased interest in these disorders and as a result treatments that work have been developed. However, a recent
review of the best psychological treatments for anxiety in children showed that on average studies are reporting
remission rates of only 56.5%. Clearly we need to develop more effective treatments for anxious children. One
possible approach to improve outcomes for children with anxiety is to provide additional treatment for the parents.
We know that anxiety runs in families: anxious children are more likely than non-anxious children to have
anxious parents. A number of theories have suggested that parental anxiety plays an important role in the
development of anxiety in children: An anxious parent may model anxious behaviour, encourage avoidance of
anxious situations and reinforce anxious behaviour in their child. The results of this study will determine whether
it is possible to improve the efficacy of treatments for anxiety in children by addressing anxiety in their parents. If
the data show no additional benefit of the modified treatment, therapists can be more efficient in their treatment of
anxious children by ignoring the parent's own anxiety. However, if as expected the modified treatment proves to
be more efficacious, then we will have identified an important strategy to increase the efficacy of intervention for
this highly prevalent and debilitating childhood problem.
Research achievements (from final report):
We know that anxiety disorders are a widespread problem in our youth. We also know that anxiety, if left
untreated, will persist through the child's life and cause significant disruption to their life. The good news is that
there has been an increased interest in these disorders and as a result treatments that work have been developed.
However, not all children respond to treatment and we need to develop more effective treatments for anxious
children. Because anxiety runs in families, the purpose of this NHMRC project was to determine whether we
could enhance outcomes for children by providing additional treatment for parents. In our study, 66.8% of
mothers and 36.2% of fathers of anxious children met criteria for anxiety disorder prior to treatment. In our study,
children's response to treatment did not depend on parent's anxiety status or parental participation in an additional
treatment component. Importantly the study showed that 65% of anxious mothers still met criteria for anxiety
disorder at the end of treatment (regardless of whether they received additional treatment). These findings suggest
that we need to provide a more intensive and targeted program for anxious parents of anxious children.
Expected future outcomes:
Future directions will involve developing more targeted and intensive programs for anxious parents of anxious
children. This project will lead to future clinical trials to enahnce outcomes for anxious children.
Name of contact:
Email of contact:
Jennifer L. Hudson
jhudson@psy.mq.edu.au
NHMRC Research Achievements - SUMMARY
Mental Health Research Institute of Victoria
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
149885
Prof Nicholas A Keks
Psychiatry
Mental Health Research Institute of Victoria
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$300,000.00
Standard Project Grant
Title of research award: Competence to give informed consent for research participation in schizophrenia and
related psychoses
Lay Description (from application):
There is current controversy surrounding the ethics of allowing people with mental illness to participate in
research. By trying to safe guard what is considered a vulnerable group, we may also be denying these people
their rights to make decisions for themselves. The potential benefits of clinical research in an area where
treatments are often ineffective and cause serious side effects may also be denied to these people. This study aims
to measure the capacities of patients with psychoses to give informed consent to participate in clinical research.
The uniqueness of this project is that subjects will be rated as either competent or incompetent according to legal
definitions applicable in Australia by utilising predetermined thresholds. We will also determine whether
performance of patients in tests of competence can be improved through an established educational program.
Additionally we plan to re-evaluate patients after a period of 6 months in order to test the reliability of competence
performance.
Research achievements (from final report):
The project determined the range and prevalence of competency issues in patients with schizophrenia or related
psychosis (N=489). In terms of capacity to give informed consent to research, patients were considerably more
competent than commonly assumed. The project incorporated the notion of context, where competency is viewed
on a sliding scale, depending on the situation. Subsequently, specific measurable levels of competency for three
common research situations were developed for clinical use. Estimates of the prevalence of impaired competency
were made and normative information for several prominent competency tests is now available from healthy
controls (N=50), patients with psychosis (N=389) and physically unwell groups (N=50). The use of several
competency measures allowed the cross-validation of an abbreviated measure of competency that can be readily
adapted to a clinical setting. Comparing each group's results indicated surprisingly little difference between the
medically unwell and the patients with psychosis. This highlights that widely held assumptions regarding
competency in patients with psychosis are likely to be incorrect. The influence of psychotic symptoms on
competency was also assessed. Only symptoms that impact globally on patient functioning, such as formal
thought disorder were associated with impaired competency. Symptoms such as delusions and/hallucinations,
although troubling to the patient, did not compromise capacity to make decisions regarding research participation.
This is of importance to patients who are commonly excluded from research because of the severity of such
symptoms. Neurocognitive testing indicated executive functioning was the most prominent predictor of
competency. Variations in level performance on tasks of memory, learning and intellectual abilities did not
significantly predict competency performance. Identification of "at risk" patients using widely available
neurocognitive tests is now therefore possible.
Expected future outcomes:
Research in psychosis has been limited by restricted patient recruitment as it is assumed these patients are not
competent to make an informed decision regarding research participation. This research suggests many of these
patients are in fact able to make such a decision. This encourages the patients' rights to autonomy and selfdetermination to seek alternative treatments as they see fit.
Name of contact:
Email of contact:
Professor Nicholas Keks
nicholas.keks@boxhill.org.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
193100
A/Pr Maarten van den Buuse
Mental Health
Mental Health Research Institute of Victoria
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$175,000.00
Standard Project Grant
Title of research award: Role of brain serotonin in animal models of schizophrenia
Lay Description (from application):
There is increasing evidence that deficiencies in the release of a brain chemical called serotonin play an important
role in the development of schizophrenia. Post-mortem studies have shown changes in the levels of 'receptors'
(keyholes for messenger chemicals in the brain) for serotonin in schizophrenia. In addition, in the treatment of
schizophrenia, the more recently introduced 'atypical' antipsychotic drugs are superior to the more traditional
'typical' antipsychotics in terms of efficacy and side-effect profile. Typical antipsychotic drugs act mainly through
blockade of receptors for a brain chemical called dopamine. Atypical drugs appear to have additional actions, in
particular blocking the effect of serotonin in the brain. This evidence is mostly circumstancial, relying to a large
extent on biochemical analysis of brain regions and 'receptors' on which antipsychotics MAY act. It is currently
unclear exactly how and where in the brain changes in serotonin activity influence behavioural processes causing
schizophrenia. It is also unclear how and where typical and atypical antipsychotic drugs interact with the role of
serotonin in schizophrenia. In this project we intend to inactivate specific parts of the serotonin system of
otherwise intact, freely moving rats. Using behavioural observation methods relevant for schizophrenia, we will
analyze if and how these interventions influence the behaviour of these rats. The results can have important
implications for our fundamental understanding of the involvement of serotonin in the brain in schizophrenia.
Research achievements (from final report):
The work in this project had led to a better understanding of the role of a messenger chemical in the brain,
serotonin, in aspects of schizophrenia. We are now able to distinguish the relative role of different cell-groups
containing serotonin. We have also been able to define how serotonin in one particular part of the brain, the dorsal
hippocampus, seems to play an inhibitory role in some of the symptoms of schizophrenia. This work was done
using laboratory studies. Clinical studies should be done focusing on serotonin in the dorsal hippocampus, to
confirm its role in human brain function and in the action of antipsychotic drugs. This may ultimately lead to new
treatments or even preventative strategies in this devastating mental illness.
Expected future outcomes:
The findings may lead to new or improved treatments against the symptoms of schizophrenia.
Name of contact:
Email of contact:
Dr. M. Van Den Buuse
mvandenbuuse@mhri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
193299
A/Pr Brian Dean
Psychiatry
Mental Health Research Institute of Victoria
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$540,000.00
Standard Project Grant
Title of research award: High-throughput screening of the genome and proteome in postmortem CNS from
subjects with schizophrenia
Lay Description (from application):
Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying
pathology of the illness remains unknown. This application seeks funding to use new technologies to screen
approximately 60% of the expressed human genome and proteome to determine which genes are being
differentially expressed in two regions thought to be important in generating the symptoms of the illness, the
frontal cortex and hippocampus. This project will generate a large amount of data, however by comparing the data
from subjects with schizophrenia to that from control subjects and subjects with bipolar disorder who were
psychotic and being treated with antipsychotic drugs close to death will allow us to identify changes that are
specific to schizophrenia. Genes that are expressing different levels of mRNA and protein will become prime
targets for future investigations as they are likely to be central to the pathology of the illness.
Research achievements (from final report):
We have complete the experimental protocols that have measured levels of mRNA for approximately 12,500
genes in the frontal cortex of subjects with schizoprhenia, bipolar disorder and age/sex matched controls. This is a
seminal work in comapring so many genes to determine which are affected in a disorder-specific manner. We
have also analysed the levels of approximately levels of approximately 3000 proteins in the same brain regions
from the same groups of subjects. We are in the process of identifying the proteins that are altered in
schizoprhenia and bipolar disorder. We are in the process of completing an analysis on tissue from 25 subjects
with schizophrenia and 25 control subjects. The magnitude of data from these experiments means there will be a
wealth of findings once a full analises is completed. We will find genes that are expressed abnormally at the level
of mRNA and proteins in the brains of subjects with schizoprhenia and bipoalr disorder. These genes will be
likely to be central to the cause of both disorders. We will use our data from the larger cohort of subjects with
schizophrenia to determine if the syndrome (a group of disease clustered under one name because of similar
symptoms) can be divided into disease using the biological measure of altered brain protein expression patterns.
The potential benefits from both approaches will be the identification of genes that are central to schizophrenia
and bipolar disorder and these genes will become targets for drugs that should turn out to be an improved way of
treating the two disorders.
Expected future outcomes:
The identification of key functional pathways in the brain that are the cause of schizoprhenia and bipolar disorder.
Identifying such pathways will open up the exciting prospect of the development of drugs, which on altering the
activity of the derranged pathway, will be useful in treating schizophrenia and bipolar disorder.
Name of contact:
Email of contact:
Brian Dean
bdean_mhri@iprimus.com.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
236175
Dr Murat Yucel
Psychiatry
Mental Health Research Institute of Victoria
Start Year:
End Year:
Total funding:
Grant Type:
2003
2004
$340,000.00
Standard Project Grant
Title of research award: Relationship between anterior cingulate morphology, neuronal integrity and function in
schizophrenia, obsessive-compulsive disorder and healthy controls.
Lay Description (from application):
Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend
to appear in early adulthood and have a number of important similarities. These include problems with planning
and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior
cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and
attention. However, it is now recognised as the interface between the emotional, feeling part of the brain and the
controlling, thinking part. Many, if not all, of the functions performed by the anterior cingulate are disturbed in
both schizophrenia and OCD, meaning that studying this region may provide important clues to the nature of the
two illnesses. One important characteristic of the anterior cingulate which has not been considered in previous
research is its division into three distinct subregions, each with their own specific function. In particular, there is a
cognitive region, which deals with response selection and information processing, and an emotional region, which
assesses motivational content and controls emotional learning. Because of the nature of the two disorders we
intend to study, we believe that schizophrenia will be associated with more abnormalities of the cognitive region,
while OCD will be associated with changes in the emotional region. Another important feature of our research
design is that we intend to collect data from the same subjects using four separate brain imaging techniques, which
provide information about different levels of brain structure and function. This will allow us to interpret our
findings from measures of brain chemistry in the context of our findings of brain function. Hopefully this will help
us to clarify the pathophysiology of schizophrenia and OCD, and provide potential ways to assess the effect of
different treatment strategies in these illnesses.
Research achievements (from final report):
The psychiatric disorders schizophrenia (SZ) and obsessive-compulsive disorder (OCD) are extremely debilitating
and associated with enormous personal, social, and economic costs. For these reasons, it is critical to understand
the cause and neurobiological mechanisms involved in order to develop effective intervention strategies to prevent
these illnesses or ameliorate their effects. There is now compelling evidence to implicate a brain region called the
anterior cingulate cortex (ACC) in the pathophysiology of both schizophrenia and OCD, but the exact nature of
how this brain region is invoved in these disorders is still unclear. Our early findings suggest that when
comprehesively examined, the specific region and side of the ACC disturbances, as well as the nature of the
disturbances (anatomical, functional, chemical etc) are markedly different between the two disorders and may
explain the differing presentations of schizophrenia and OCD. Specifically, the SZ patients showed anatomical
abnormalitites together with reduced N-acetylaspartate (NAA; a marker of neuronal/axonal integrity) levels and
associated reduction in blood oxygenation level dependent (BOLD) activation in the left cog-ACC during
performance of a cognitive interference paradigm, while OCD patients showed no anatomical abnormalitites,
preserved dorsal-ACC neurochemistry and activation but increased creatine/phosphocreatine and choline levels
(Cr; Cho; markers of increased energy metabolism and myelin/membrane turnover) in the right aff-ACC. These
early findings demonstrate the complexity of ACC involvement across psychiatric disorders, and suggest that the
side, subregion and type of dysfunction are key parameters for understanding ACC involvement in the
pathophysiology of these conditions.
Expected future outcomes:
Future outcomes include more compreheive analyses of existing data to more clearly determine the unique and
overlapping contributions of this part of the brain to the abnormal behviours seen in schizophrenia and OCD. This
should provide benefits in terms of understanding the mechanisms that can lead to psychotic and anxiety
disorders.
Name of contact:
Email of contact:
Dr Murat Yucel
murat@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
236025
Prof David L Copolov
Psychiatry
Mental Health Research Institute of Victoria
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$285,000.00
Standard Project Grant
Title of research award: The Neurobiology of Auditory Hallucinations: Characterisation of dysfunction with in a
neural circuitry model.
Lay Description (from application):
This is a highly innovative research proposal which is based on years of extensive research by our group. Auditory
hallucinations are a prominent and potentially disabling symptom of psychosis, however it is extremely difficult to
study them scientifically. Past research by our group (and other groups internationally) has indicated that an
extensive network in the brain is activated whenever auditory hallucinations occur, but the source of this brain
activity is unclear. It was thought that the source may be the same brain circuits that are involved in generating
"inner speech" or monitoring it, but our past research has ruled out these possibilities. Instead, our recent work
suggests that auditory hallucinations may be associated with poorly functioning connections within central
auditory processing circuits, specifically between left and right auditory association cortical regions. We
conceptualise hallucinations as an abnormal and involuntary form of memory retrieval consequent to this
dysfunction. Our study will pioneer methods of measuring connectivity in the brain circuits identified in our
model, using a combination of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG)
techniques in tandem with tests of central auditory processing. We believe that sufferers may benefit from
understanding the physical processes which cause hallucinations. We also believe that a better understanding of
hallucinations may lead to a better understanding of schizophrenia and the psychoses, which may in turn help in
the development of better ways of treating these illnesses.
Research achievements (from final report):
This was a study of the neurobiology of auditory hallucinations (AHs), the perception of sounds in the absence of
auditory stimuli. The study was centered on testing a novel neural circuitry model which encapsulates the findings
by our group from a series of NH&MRC-funded studies. It is generally accepted that large neuronal networks
need to be functionally integrated for normal perception of complex stimuli such as language sounds, but few
models of AHs have been formulated in terms of such a functional integration. The project was conducted as a
multimodality study involving DTI, EEG, and fMRI activation and connectivity estimates across three groups:
patients with AH (AH), non hallucinators (nAH), and normal controls (C). The study also involved a complete
clinical and behavioral assessment. In agreement with our model, the results from three datasets (audiology,
functional magnetic resonance imaging connectivity measures and diffusion tensor imaging) have all indicated
that AH patients show deficits in interhemispheric transfer of information between the auditory cortices. We have
further suggested that patients with AH demonstrate reduced volume within the primary auditory cortices and not
the secondary. An important outcome of this study is the identification of damaged regions and networks. We do
not claim that the model is complete, but we suggest that validation of the role of each of the components
described here may enable extensions to the model which will render it more complete, and perhaps will
eventually account for all the characteristics of AHs.
Expected future outcomes:
There needs to be a more detailed examination of the behavioral consequences of impaired interhemispheric
connectivity in AHs, for example are impairments at all levels of sound processing (pitch, amplitude and length
discrimination). Further, there needs to be more research to determine whether such behavioural problems can be
cognitively remediated.
Name of contact:
Email of contact:
David Copolov
David.Copolov@adm.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
236100
Prof David J Castle
Psychiatry
Mental Health Research Institute of Victoria
Start Year:
2003
End Year:
2005
Total funding: $345,250
Grant Type: Standard Project Grant
Title of research award: A Randomised Control Trial of a Group Based Intervention for Substance Use and
Psychosis
Lay Description (from application):
The use of alcohol and illicit substances is common amongst people with psychotic illnesses, and is associated
with a poor outcome in terms of severity of symptoms, treatment adherence, work/studies, family cohesion,
aggression and quality of life. All this adds significantly to the cost of mental health services and society more
broadly. The proposed study aims to refine, pilot, and rigorously evaluate a group-based intervention that targets
substance use in such individuals at different stages of their illness, and within a number of different treatment
settings. The intervention will be informed by an enhanced understanding of the motivations for substance use in
people with psychotic illnesses The specific aims are to: 1. Refine, implement and evaluate, using a controlled
experimental design, a novel group-based intervention for reducing substance abuse comorbidity in people with
psychotic disorders; 2. Determine reasons for substance use by these individuals, to inform the intervention
procedures; 3. Pilot the intervention in a series of different treatment settings, including early episode and
rehabilitation programs, and non-government organisations dealing with people with psychotic disorders, to
ensure generalisability, adaptability, and acceptability; 4. Augment case managers' knowledge and skills in dealing
with comorbid drug and alcohol use; 5. Enhance detection, motivation to change, ongoing monitoring and relapse
prevention of substance misuse in clients with psychotic disorders. It will also be possible, once the treatment
intervention is finalised and evaluated, to expand its use to patients with non-psychotic mental illnesses.
Research achievements (from final report):
This project has developed and evaluated a treatment manual for people with problematic substance use and
psychosis(dual diagnosis). Outcomes to date are showing a reduction in the amount of legal and illegal substances
used by the individual once they have completed the program. Early results suggest these outcomes have been
sustained 12 months after becoming involved in the dual diagnosis program. The implications of this reduction in
problematic substance use is reflected in the person's own reporting of improved quality of life since completing
the program. Importantly, people with dual diagnosis often do not seek help or maintain support networks that can
assist with relapse prevention strategies. Preliminary results suggest a positive increase in their engagement with
key support people such as general practitioners. Alongside this manualised intervention we have developed
training workshops to enhance workforce capacity in a wide range of government and non-government services.
The use of the manual and accompanying service delivery framework to ensure long term sustainability has
attracted interest and active involvement by services nationwide. The long term benefit to people with dual
diagnosis is the capacity for services to respond to the needs of this highly vulnerable and often marginalised
population by improving the skills of clinicians and routinely providing effective interventions.
Expected future outcomes:
That Drug and Alcohol, non -government organisations and mental health services have access to an evidence
based best practice intervention for substance use and psychosis.
Name of contact:
Email of contact:
Monica Gilbert
mgilbert@mhri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
282935
A/Pr Maarten van den Buuse
Psychiatry
Mental Health Research Institute of Victoria
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$318,500.00
Standard Project Grant
Title of research award: Modeling the two-hit hypothesis of schizophrenia: combined neonatal stress and
postnatal corticosterone treatment in rats
Lay Description (from application):
Schizophrenia is a severe mental illness defined by a number of symptoms including hallucinations, delusions,
social withdrawal and cognitive impairment. Factors very early in development have been suggested to induce an
increased vulnerability to this illness. Recently, it was suggested that another major event, later in life, would be
needed before vulnerable individuals would develop schizophrenia. The aim of this project is to model this "twohit" hypothesis in rats. We will compare the effect of various neonatal maternal separation protocols as an early
stressful event, followed by chronic treatment with the stress hormone corticosterone at various stages later in life.
We will also perform a detailed anatomical study of the hippocampus of these rats. This brain area has been
implicated in the development of schizophrenia in humans. We will also investigate if treatment with
antipsychotic drugs can prevent or reverse behavioural and neuroanatomical changes seen in the rats. This will be
the first comprehensive study to model this "two-hit" neurodevelopment hypothesis of schizophrenia and will
provide an experimental verification of a clinical concept which is very difficult to prove in patients.
Research achievements (from final report):
It has been hypothesised that schizophrenia is caused by two or more developmental disruptions during the
lifespan. Epidemiological studies suggest that the first disruption occurs during an early stage of brain
development and causes an increase in the vulnerability for developing the disease. A second stressful disruption
that occurs later in life, for example psychosocial stress or drug abuse, is required to trigger the onset of the
disease. The aim of this study was to develop and investigate a new neurodevelopmental animal model of
schizophrenia combining an early disruption (maternal deprivation) and a late disruption (chronic corticosterone
administration) in rats. These animals were tested in behavioural models with relevance for schizophrenia. Taken
together, the experiments are providing new insight into the combined effects of early developmental stress
(neonatal maternal deprivation) and peri-adolescent stress (corticosterone treatment). These results could be
important for our understanding of the aetiology of schizophrenia.
Expected future outcomes:
Further research to detail the brain mechanisms involved in the behavioural effects of two neurodevelopmental
stress events. Future implications may include novel treatment strategies.
Name of contact:
Email of contact:
A/Prof M Van Den Buuse
mvandenbuuse@mhri.edu.au
NHMRC Research Achievements - SUMMARY
Menzies Research Institute
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
290538
Dr Kristy A Sanderson
Mental Health
Menzies Research Institute
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2004
2007
$259,000.00
Public Health (Australia)
Title of research award: The individual and societal burden of mental health problems in working adults.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Depressive and anxiety disorders are common in the workforce and potentially costly, yet too few employees seek
treatment. Employees with these disorders are also more likely to keep working when sick, transferring much of
the economic consequences to the workplace. Novel approaches to reduce this significant individual and
economic burden are needed. This postdoctoral research program explored the nature of work disability (lost
productivity) in employees with depressive and anxiety disorders, to identify potential targets for early
intervention and prevention. We investigated the mental health and productivity of a cohort of adults working in
the call centre industry over a 12-month period. We found that: i) depressive and anxiety disorders were common
and strongly associated with both work absence and "presenteeism" (coming to work when sick) ii) how
presenteeism is measured was important, as not all available tools were equally sensitive to the types of deficits in
work performance that can be experienced by employees with depressive and anxiety disorders iii) working
environments that were characterised by unfairness in dealings with employees, or where the employee felt their
work efforts were not adequately reciprocated through financial and other workplace benefits, increased the risk
for both poorer mental health and lower productivity over time. These findings have important implications for
how employees, employers, and clinicians approach depression and anxiety in the workforce, and potentially,
other chronic diseases. We are currently investigating some potential solutions to this urgent public health issue,
including collaborations with industry partners.
Expected future outcomes:
We are currently exploring how to balance the potentially competing interests of employer and employee in terms
of when the employee should keep working when ill. We are also working with managers on an intervention
designed to reduce risks to mental health from managerial processes.
Name of contact:
Email of contact:
Dr Kristy Sanderson
kristy.sanderson@utas.edu.au
NHMRC Research Achievements - SUMMARY
Menzies School of Health Research
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
137219
Dr Alan R Clough
Indigenous Health
Menzies School of Health Research
Start Year:
2001
End Year:
2003
Total funding: $304,814.00
Grant Type: NIDS Project - National Illicit
Drugs Strategy 16
Title of research award: Cannabis use in two remote indigenous communities: prospects for a population based
intervention
Lay Description (from application):
The proposed study is a combined intervention and summative evaluation with two parallel strands. We proposed
to develop, deliver and evaluate an educational instrument targeting the use of cannabis amongst Aboriginal
people living in remote communities in the Northern Territory. Additionally we proposed to describe and model
harmful behaviours and effects of substance misuse with a focus on cannabis and to explore in some detail
Aboriginal cultural knowledge and attitudes towards harm and harmful behaviours related to substance misuse
using self-reported estimates and life histories.
Research achievements (from final report):
This project documented for the first time the likely extent of cannabis use in some remote Aboriginal
communities amongst those aged 13-36 years. It confirmed previous reports by the Chief Investigator which
alerted health practitioners and policy makers to a rapid rise in the use of cannabis in isolated communities in the
'Top End' of the NT. The project documented adverse mental health effects, especially symptoms of anxiety and
dependency, that have emerged in these groups despite many of the participants in the study having used cannabis
for quite brief periods, usually around 4 to 5 years at the time the baseline survey was carried out. The project also
reported the extent of polydrug use, particularly petrol sniffing, which was more clearly associated with symptoms
of mood disorders amongst the group studied. The project also documented some social and economic impacts of
cannabis in these areas. The rapid rise in cannabis use is believed to be related to an expansion of local trafficking
especially from the late 1990s. This information is consistent with NT Police intelligence and this has led to a
focus by enforcement on the trafficking of cannabis to remote communities. An education resource was developed
which focused on neurological aspects of drug actions with an emphasis on cannabis and inhalants. This resource
is now being used in similar settings by the NT Department of Health and Community Services.
Expected future outcomes:
We have conducted follow-up assessments of the cohort recruited for baseline survey. These data will be
published to describe the affects of community-wide changes and individual responses to the education strategies
and community interventions developed and implemented during the course of the study.
Name of contact:
Email of contact:
Alan Clough
Alan.Clough@nt.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
283325
Dr Sheree J Cairney
Indigenous Health
Menzies School of Health Research
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2004
2008
$259,000.00
Australian Clinical Research
Title of research award: The development of culturally-appropriate cognitive assessments with applications in
substance abuse and mental health with Indigenous clients
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
This project successfully developed and validated several assessments of brain function and mental health in
Indigenous adults and adolescents. These included a computerised cognitive assessment (CogState), a social and
emotional wellbeing assessment (Strong Souls), eye movement recording and analysis, voice acoustic analysis and
basic neurological (motor) assessments. These assessments were used and validated among Indigenous adults and
adolescents from remote and urban regions in a range of settings including primary and high schools, adult
education institutes, prisons, communities and rehabilitation centres for substance misuse. In addition to validating
that these assesments were culturally appropriate for use with Indigenous populations, the collected data was also
used to better understand the neurological, psychological and behavioural manifestations of impairment caused by
mental health problems or substance misuse. This information has been used to inform medical professionals,
health workers, educators and policy makers. The validated assessments may now potentially be used in primary
care and research and therefore have the potential to improve services for Indigenous people in these areas.
Furthermore, novel educational resources and techniques were developed during the course of this project to
communicate the findings of the research to the Indigenous people affected. These resources and various media
output combined have raised awareness of the impact that substance abuse and mental illness has on the brain and
behavior for Indigenous people and for the wider community.
Expected future outcomes:
These novel methods of assessing and understanding mental illness and brain dysfunction among Indigenous
people may be used to identify related impairments in this area and treat them appropriately. They can also be
used to understand specific conditions and their related cognitive and psychological decline, and consequently
identify more appropriate interventions and prevention strategies.
Name of contact:
Email of contact:
Sheree Cairney
Sheree.Cairney@menzies.edu.au
NHMRC Research Achievements - SUMMARY
Monash University
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
143547
A/Pr Benedict J Canny
Endocrinology
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$408,550.00
Standard Project Grant
Title of research award: How commonly used psychoactive drugs affect the hypothalamo-pituitary-adrenal axis
Lay Description (from application):
The body makes a number of responses when it is subjected to stress, and these include the secretion of hormones
from the adrenal gland, including cortisol. It is not surprising that cortisol has effects upon the way the brain
operates, nor is it surprising that diseases that are associated with stress (e.g. depression, alcoholism and other
psychiatric complaints) create abnormal cortisol secretion. The drugs that are known to be successful in treating
conditions such as depression and anxiety have been shown to affect the secretion of cortisol, but, somewhat
paradoxically, we do not precisely know how they operate. The aim of this research is to examine how drugs that
are commonly used for the treatment of a number of psychiatric conditions (e.g. Prozac, Tofranil, Xanax,
morphine and naltrexone) affect the secretion of hormones from the brain that ulitmately regulate the secretion of
cortisol. We propose that the effects of these drugs is related to how they operate, and for how long they have
been given. The findings generated by this research may help us determine new ways of diagnosing and treating a
range of conditions.
Research achievements (from final report):
The investigations carried out as part of this award examined how antidepressant drugs affected the secretion of
stress hormones. We identified that the newer classes of antidepressant drugs stimulated stress hormone secretion,
where older ones didn't. Furthermore, the effect on hormone secretion differed between males and females, and
was affected by sex hormones. These observations were novel, and may provide insight and understanding into
how the antidepressant drugs achieve their therapeutic actions and why some dirgs seem to work better in one sex
compared with the other. In addition, the observations suggest that the acute hormonal response to the
administration of antidepressants may give an indication of the whether an individual might respond to the drug or
not. This is potentially important, as in normal clinical practice, one might wait up to six weeks before a
therapeutic effect is evident.
Expected future outcomes:
The obsevrations we have made may provide new insight into how antidepressants work, why men and women
seem to respond differently to common treatments, and could provide new diagnostic tests to help predict what
drug is the best to assist a person with depression.
Name of contact:
Email of contact:
Ben Canny
ben.canny@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
143651
Prof Paul Fitzgerald
Psychiatry
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$351,775.59
New Investigator
Title of research award: A Double-Blind Placebo Controlled Trial of Transcranial Magnetic Stimulation in the
Treatment of Depression
Lay Description (from application):
Depression is a severe and often disabling illness that occurs frequently in the general population. Depression is a
treatable illness and the majority of patients will respond to anti-depressant medication, a form of psychotherapy
or a combination of these. However, a significant percentage of patients with depression fail to respond to these
therapies and currently require electroconvulsive therapy (ECT). This entails the complications and costs of
multiple anaesthetics, memory impairment and substantial social stigma. Transcranial magnetic stimulation is
being researched as a potential alternative for these patients. It is administered to patients who are awake and alert
and appears to have fewer side effects. TMS uses the unique properties of a magnetic field to produce or disrupt
electrical activity in superficial areas of the brain, targeted to the areas thought to be involved in the cause of
depression. Our research study will compare the two most promising types of TMS with an inactive or placebo
condition. This is important to establish that the effects of TMS arise from the actual stimulation and to investigate
whether one of two types of TMS administered is superior. We will administer this treatment for between 2 and 4
weeks and assess the response. We anticipate that our research will contribute to the development of TMS as a
treatment methodology for this important patient group. It is crucial that a new treatment be thoroughly evaluated
prior to wide dissemination of it in clinical practice. We will help define the effectiveness of this treatment and the
most appropriate way in which it can be administered.
Research achievements (from final report):
The research conducted to date firmly establishes the efficacy of TMS as a treatment for depression. However,
only a subpopulation of the patients studied responded to the treatment and there is a pressing need to expand the
research to improve the patient response rates. We are doing this by investigating the value of bilaterally applied
TMS stimulation. We are also using functional brain imaging to study how the technique works. Finally, we are
planning to conduct a study of a targeting technique which we believe will substantially improve the overall
response rate to the treatment. There is also growing and considerable interest in the use of the technique in other
patient populations such as post traumatic stress disorder and schizophrenia. The overall goal is to define the
clinical role of the technique and its place across clinical conditions and to disseminate this work to allow access
to greater numbers of patients
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
143654
Prof Jayashri Kulkarni
Psychiatry
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$297,396.00
Standard Project Grant
Title of research award: Estrogen - A potential new treatment for women and men with schizophrenia
Lay Description (from application):
Estrogen - the major female hormone, has been shown in animal studies to decrease the two main brain chemicals
(dopamine and serotonin) that are implicated in causing schizophrenia. The effect of estrogen in the brain is
similar to current antipsychotic drugs. We have carried out a study that showed that when we gave 12 young
women with schizophrenia 100 micrograms of estrogen in a skin patch form plus standard antipsychotic drug
treament they recovered more quickly than 12 young women who received standard antipsychotic drug treatment
only. 100mcg is a safe dose of estrogen. In this proposal we want to expand and clarify the pilot study resutls by
conducting a 28 day trial in a total of 60 women with schizophrenia. 30 women would receive 100 mcg skin patch
estrogen plus antipsychotic medication and 30 women would receive antipsychotic medicationly only. We also
tested the value of adding a very small dose of oral estrogen to antipsychotic drug treatment in five men with
schizophrenia and found that they made a better recovery compared to five men who received standard
antipsychotic drugs only. We trialled the use of estrogen for seven days in men, but this may not have been long
enough to examine the real impact of estrogen treatment in men. In this proposal we want to conduct a 14 day trial
in a total of 60 men with schizophrenia. 30 men would receive 2mg of oral estrogen plus antipsychotic drug
treatment and their results would be compared with 30 men who received standard antipsychotic drug treatment
plus a placebo tablet identical in appearance to estrogen. For 14 days, this low dose of estrogen is very safe.
Potentially estrogen may be a useful addition to the current standard treatment of schizophrenia. It may decrease
the duration of acute illness and in women it may have a role in preventing relapses of schizophrenia as well as
improving the general health of women with schizophrenia.
Research achievements (from final report):
These studies were clinical trials aimed at exploring whether estrogen - the major female hormone - has a
protective effect against schizophrenia in both women and men. Estrogen has been shown in animal studies to
decrease the two main brain chemicals (dopamine and serotonin) that are implicated in causing schizophrenia.
Estrogen has also been reported to affect aspects of cognition and abnormal behaviour in women, both normal and
with psychosis. Two studies were conducted: (1) a study of 81 women of child bearing age with schizophrenia,
who received standardised antipsychotic medication plus either estradiol (100mcg) or placebo patches showed that
women receiving estradiol made significantly greater improvements in the symptoms of schizophrenia than those
in the placebo group. There were also some significant improvements for women receiving estradiol in some areas
of cognition, compared to women receiving a placebo. (2) a study of 52 men with schizophrenia who received
standardised antipsychotic medication plus either oral estradiol valerate (2mg) or placebo showed that men with
higher estrogen levels improved more than men with low estrogen levels.
Expected future outcomes:
The duration of the"antipsychotic" effect of estrogen on schizophrenia symptoms was not measured in this
estradiol study. Thus, we now propose to study the use of adjunctive estradiol in a sample size of 200 women and
follow up their progress across 6 months. We also intend to incorporate approaches to understanding more about
the aetiology of estrogen action in schizophrenia.
Name of contact:
Email of contact:
Professor Jayashri Kulkarni
jayashri.kulkarni@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
194238
Start Year:
2002
CIA Name: Prof Bruce J Tonge
End Year:
2003
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$120,220.00
Admin Inst: Monash University
Grant Type: Standard Project Grant
Title of research award: An examination of motor functioning in autism and Asperger's disorder: An analysis of
gait & cortical brain activity
Lay Description (from application):
Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language
development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of
the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar
to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy,
have a stiff or awkward way of walking, and exhibit poor coordination in posture and gesture. It has been
suggested that there is disruption within the basal-ganglia-thalamocortical circuitry (the region connecting the
frontal and sub-cortical structures), which may cause the motor dysfunction seen in autism and Asperger's
disorder. Few studies have attempted to isolate particular stages of motor functioning which may account for the
coordination and motor delay observed clinically in autism and Asperger's disorder. A recent study of ours found
evidence to suggest that motor planning deficiencies may account for the 'clumsy' movement patterns frequently
reported in the autism / Asperger's disorder literature. Therefore, the aim of this research is to provide a
comprehensive neurobehavioural and neurophysiological analysis of motor functioning in young people with
autism and Asperger's disorder to further examine the exact stages of motor processing which are deficient in
these disorder groups. Recent retrospective studies have shown that even as infants children with autism exhibit
clear features of motor disturbance, which, if detected and clearly defined, could advance early diagnosis. In
addition to advancing the clinical definition of autism and Asperger's disorder, a careful examination of motor
disturbance may also illuminate the neurobiological underpinnings of these disorders.
Research achievements (from final report):
While abnormal motor signs and symptoms are often noticed by the parents of children with autism and
Asperger's disorder, to date there has been very little research which has sought to systematically describe and
understand the basis of these motor impairments. Clinicians working in the area of autism and Asperger's disorder
have debated for some time whether children with autism may have specific motor problems which are distinct
from those observed in children with Asperger's disorder. This research has uncovered very distinct patterns of
motor disturbances which distinguish children with autism and Asperger's disorder, and leads us closer to
understanding the underlying brain dysfunction of these disorders. The next important step is to convert our
experimental findings about motor functioning into assessment tools which may expedite the early diagnosis of
children with autism/Asperger's disorder. We also hope to extend this research into the therapeutic arena and make
recommendations for the remediation of motor symptoms which impair the quality of life of affected children.
Lastly, this reasearch now lays the ground work for more focussed neurobiological research to clarify the brain
disruption which underpins these disorders.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
236807
Prof Paul Fitzgerald
Psychiatry
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$185,000.00
Standard Project Grant
Title of research award: A TMS Study of Cortical Plasticity in Schizophrenia
Lay Description (from application):
The cause of schizophrenia is uncertain. Several lines of evidence implicate abnormalities of functioning in
circuits of nerve cells in the outer brain regions. Chemicals involved in these circuits are important for the
capacity to learn and process new information and repeated exposure to stimuli. To date, it has been difficult to
directly test the function of these circuits in patients with schizophrenia. Transcranial Magnetic Stimulation
(TMS) is a non-invasive means of stimulating nerve cells in superficial areas of the brain. During a TMS
procedure, an electrical current passes through a coil placed close to the scalp. This current induces a magnetic
field that stimulates electrical activity in nerves below the coil. TMS methods can be used to study the functioning
of nerve cells in the brain and the way in which they respond to repeated stimuli. These methods will be used in
this way to study the functioning of these circuits in patients with schizophrenia. This is likely to provide
important information as to the function of these brain areas and may provide information that will guide the
development of therapeutic interventions.
Research achievements (from final report):
Five publications and 2 international seminars arose from the completion of this study; the exposure and
dissemination of information is valuable in stimulating recognition for important research conducted in Australia,
specifically that funded by NHMRC. This is the first study to directly demonstrate the abnormality of a 'plastic'
brain process in patients with schizophrenia (indeed any psychiatric disorder). This finding has stimulated
additional research into questions which will help us better understand the neuropathology of schizophrenia.
Ultimately, research of this sort will inform clinical understanding and treatment of the disorder.
Expected future outcomes:
Current research inspired through this grant will endevour to explore more specific brain processes in
schizophrenia and expand the current findings to other brain areas.
Name of contact:
Email of contact:
A/Prof Paul Fitzgerald
p.fitzgerald@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
236834
Prof Bruce J Tonge
Psychiatry
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$252,500.00
Standard Project Grant
Title of research award: Early detection of infants and young children with autism
Lay Description (from application):
Autism is a severely handicapping condition adversely affecting social interaction, communication, behaviour,
interests, and activities. Autism requires treatment at an early age (before 4 years). Despite finding that parents
notice problems with their child's development within the first 2 years, on average diagnoses are made around 6
years of age. Treatment for autism should begin as early as possible to improve outcome. Diagnosis requires
specialist assessment and these services are limited. Therefore it is not possible to undertake such assessments
with all children who have developmental problems. This project therefore proposes to evaluate a method for
screening large populations of children for autism, thus enabling timely and more appropriate referral to
assessment services. Previous work by the investigators has developed a potential screening tool (DBC Early
Screen) for autism in young children under 4 years with developmental delay that has high levels of accuracy in
identifying those infants and children who are at risk of autism and require specialist assessment. This project
proposes to undertake a community field trial to assess the accuracy and reliability of this early screen and to
establish its suitability for wide use as a population screening tool. The preliminary testing of DBC Early Screen
demonstrated that a community field trial was feasible. The results of this study will facilitate the referral of
infants and young children to specialist autism assessment services, thus enabling the commencement of
appropriate early intervention for children and their families from an early age.
Research achievements (from final report):
This research established a reliable and effective screening tool (DBC Early Screen) for Pervasive Developmental
Disorders (autism) in young children with developmental delay. The development and subsequent use of such a
tool will then assist in ensuring that infants and young children are referred to specialist assessment teams (a
scarce resource) in order to receive prompt assessment and diagnosis, thus enabling the earliest possible
commencement of intervention and support for the child and family.
Expected future outcomes:
This will result in the development of a DBC Early Screen package for use with primary care physicians and early
childhood services. This will ultimately assist in the identification of young children who require referral to
assessment services.
Name of contact:
Email of contact:
Dr Kylie Gray
kylie.gray@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
250600
Dr Britt Klein
Mental Health
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$202,575.00
Standard Project Grant
Title of research award: A randomised controlled trial of internet-based therapy for panic disorder
Lay Description (from application):
Approximately 9.7% of the adult population have an anxiety disorder with one of the more common, panic
disorder, often with agoraphobia, afflicting 2.4% of the community. Around 8% of patients consulting a GP also
have panic disorder (PD). A further 10% of the community experience spontaneous panic, but do not have full PD
(termed non-clinical panic). People with PD frequently experience clinical depression, about 15% abuse alcohol
and non-prescription drugs and PD is associated with an increased risk of suicide. Over time people with PD
appear to have an increased risk of heart problems. They also have substantial financial burdens through multiple
attendances at doctors' rooms and through restricted employment opportunities. Only just over one in four people
with an anxiety disorder consults a health professional for their problems, with most going to their GP. It has been
estimated that less than 10% of these people seek the services of a mental health specialist such as a clinical
psychologist or psychiatrist. Therefore because of blocks to do with access, cost or embarrassment, many people
with mental health problems do not seek face-to-face specialised mental health treatment. People in rural and
regional Australia are particularly disadvantaged by limited access to these specialists. We have developed an
internet-based treatment program on panic and anxiety for people in the community, and particularly in regional
Australia. Early evaluation of this program has found it is more effective than other types of therapist-assisted
self-help treatment. The aim of this research project is to compare it to best-practice face-to-face psychological
and pharmacological treatment for PD. If the effectiveness of our internet-based treatment is comparable to bestpractice face-to-face treatment, its availability will assist the many Australians who suffer from debilitating panic
but who are unable to access specialised mental health assistance.
Research achievements (from final report):
This study demonstrated that internet-based treatment for panic disorder could achieve equivalent patient
outcomes to the traditional 'gold standard' face-to-face cognitive-behavioural therapy with a psychologist. This is
significant as internet-based treatment is less expensive, and far easier to access, than face-to-face specialist
support. Furthermore, this study provided preliminary evidence (although not via a randomised trial) that the
internet-based treatment achieves comparable patient outcomes to anti-depressant (selective seratonin reuptake
inhibitor) medication. This study, therefore, provides a basis on which to develop further internet-based programs
for other psychological (and perhaps physical) health conditions. In the future, we are likely to see a proliferation
of efficacious internet-based treatment programs that will serve to increase accessibility to specialist mental health
treatment, at a lower cost and less inconvenience, and potentially therefore increase compliance.
Expected future outcomes:
1) Publication of four international peer-reviewed publications and be the first internationally to publish a RCT
outcome paper in this area. 2) Seek funding to automate Panic Online and conduct a comprehensive costeffectiveness trial. 3) Integration of Panic Online into the health system via a commercial arrangement.
Name of contact:
Email of contact:
Dr Britt Klein
britta.klein@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
284303
Prof Bruce J Tonge
Psychiatry
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$428,250.00
Standard Project Grant
Title of research award: A parent education and skills training intervention for young adolescents with autism
Lay Description (from application):
Autism is a most severe and prevalent lifelong developmental disorder affecting approximately one in every
thousand children and their families. Autism is associated with personal suffering and is a significant burden and
stress for parents, families and carers and cost to the community. In earlier work we have demonstrated that
providing a structured program of parent education and guidance to families with preschool children with autism
leads to improved parental adjustment and mental health. The program also led to behavioural and developmental
benefits for the child. The early secondary school years bring further stress and difficulty to adolescents with
autism and their families. This project aims to assess the effectiveness of a parent education and training program
for parents with autistic adolescents aged 12-14 years. If shown to be effective, this manual based intervention can
be readily used by professionals to promote parent mental health, family adjustment and improve the wellbeing
and outcome for adolescents with autism. As a result, family stress and the necessity of out of home care may be
reduced and school participation improved.
Research achievements (from final report):
This project began in 2004 and is expected to be completed in December 2008. NHMRC funding covered 2004-6.
Aims of the study (1) determine whether a specific parent education and behaviour management skills training
intervention improves the behavioural, developmental, language, adaptive functioning, and symptomatic outcome
for young adolescents with autism relative to an age, sex, and developmental level matched community sample of
early adolescents with autism who do not receive these specific interventions; (2) determine if this parent
education and skills training intervention improves the mental health and well being of the parents and family
functioning and (3) assess the maintenance of therapeutic gains over time. Autism is a most severe and prevalent
life-long developmental disorder affecting approximately one in every thousand children and their families. The
transition into adolescence for young people with autism is associated with an exacerbation of considerable
personal suffering and extra burden and stress for parents, families and carers and cost to the community. 50
parents have competed the parent education and skills training programme. Parental mental health and child
behaviour and adjustment outcome measures will be compared with 50 non treatment controls at one and two year
follow up. Preliminary evidence indicates that a structured parent-based behaviour management skills training
intervention improves parental mental health post intervention (P
Expected future outcomes:
It is anticipated that the parent intervention will lead to improved parental mental health and adjustment and that
professionals will be trained to implement the progarmme across Victoria and then more broadly.
Name of contact:
Email of contact:
Prof Bruce Tonge
bruce.tonge@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
284319
Prof Jayashri Kulkarni
Psychiatry
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$250,500.00
Standard Project Grant
Title of research award: Anti-Estrogens - A Potential Treatment for Bipolar Affective Disorder in Women?
Lay Description (from application):
Bipolar Affective Disorder (BPAD) or "Manic-Depressive Illness" is a serious mental illness with high morbidity
and mortality. The cause of the illness is still unclear and the underlying neurochemical changes are different for
the manic phase compared with the depressive phase. The current treatments for BPAD are limited in scope and
not biochemically well understood. There are gender differences in the presentation and outcomes for BPAD
which adds to the complexity of the illness. We are proposing a study to develop a new type of treatment for the
manic phase of BPAD and are exploring the use of anti-estrogens in women with mania. The background to our
proposed study comes from a few case reports suggesting that anti-estrogen agents such as progesterone and
tamoxifen may be useful adjuncts to treatment. We conducted a small pilot study comparing the addition of oral
tamoxifen with oral progesterone and placebo in 10 women with mania and found that the women who received
tamoxifen made significantly better improvements in their manic symptoms over a 28-day trial. The research
study we are now proposing is a larger, three-arm, double blind, placebo controlled, 28-day adjunctive study in
women with mania to expand and clarify our pilot study findings. Patients in our proposed study would receive
either 40mg per day tamoxifen or 20mg per day progesterone or placebo in addition to standardised lithium
medication. We will measure enzyme activity (protein kinase C) and estrogen/progesterone levels to understand
more about the mechanisms of action by these new hormone treatments. BPAD is a crippling disorder and if we
are successful, then tamoxifen treatment may be an important new treatment. This proposed study will also shed
new light on some of the neurochemical mechanisms underlying BPAD as well as opening up the new area of
hormone treatments for serious mental illness.
Research achievements (from final report):
A gender focus on mental health issues has a great deal to offer in developing new understanding, new treatments
and prevention of mental illnesses. Women have not received enough attention as a specific group in terms of
studying the biological and psychosocial causes and impacts of mental illness. Throughout recent history,
medicine has deemed that the "standard" patient is the "70 kilogram man" and health professionals are taught to
develop treatment and diagnostic strategies around this archetypal patient. In considering sex differences in the
onset, course and outcomes of mental illnesses, we have a powerful stimulus to developing new aetiological
theories and treatments. This research examined the role of hormone modulation as a treatment for mania for
women with schizoaffective and bipolar affective disorder. Fifty-one females participated in this double-blind
placebo controlled trial and were randomised to receive either a placebo or one of two 'anti-estrogen' treatments
(in addition to their standard medication) for the 28-day trial period. Results indicated that all groups
demonstrated a significant reduction in symptoms of mania over the trial period. While there were no significant
differences between the groups, anecdotal reports, as well as secondary analyses demonstrating a preferential
response to the anti-estrogen tamoxifen in patients with bipolar affective disorder patients compared to women
with schizoaffective disorder. These results strongly suggest that further research needs to be conducted in the use
of hormone modulation as a treatment for mania.
Expected future outcomes:
Extensive research is still needed in the area of women's mental health to better understand and develop tailored
treatments for women with mental and cognitive disorders. The overall awareness of the importance of issues
affecting women's mental health needs to improve, so that new insights can lead to new treatments with better
outcomes for women's mental health.
Name of contact:
Email of contact:
Professor Jayashri Kulkarni
j.kulkarni@alfred.org.au
NHMRC Research Achievements - SUMMARY
Grant ID:
237027
Start Year:
2003
CIA Name: Dr Mark A Rogers
End Year:
2007
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$392,513
Admin Inst: Monash University
Grant Type: Neil Hamilton Fairley Fellowship
Title of research award: Executive control of attention and cognition in schizophrenia and depression
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
A reduction in amygdala volume was observed in persons who had been exposed to sarin gas in the Tokyo
subway sarin attack of 1999 and who later developed post traumatic stress disorder (PTSD). As this volume
reduction was not observed in individuals exposed to sarin who did not later develop PTSD, the findings suggest
that structureal abnomality of the amygdala may be involved in the neuropathology underlying the disorder. These
findings, when considered together with evidence of anterior cingulate abnormality and of the white matter
interconnecting the amygdala and the anterior cingulate offer support for the hypothesis that PTSD represents a
failure of the normal extinguising of learned fear.
Expected future outcomes:
The Australian based component of the fellowship has continued the investigation of structural brain changes and
trauma. This research, into the relationsgip between early life trauma and hippocampus volume change in
depression is still ongoing. This work will help clarify the relative involvement and interaction of early life trauma
and depression with respect to hippocampus volume.
Name of contact:
Email of contact:
Mark Rogers
mark.rogers@deakin.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
400133
Prof Arthur Christopoulos
Basic Pharmacology
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$447,750.00
Standard Project Grant
Title of research award: Novel modes of regulation serotonin 5HT2C receptors.
Lay Description (from application):
The normal function of all living cells depends on how they respond to the multitude of physical and chemical
stimuli to which they are constantly exposed. The majority of these stimuli acting on cells do so not by directly
entering the cells, but rather by acting on specific types of "receiver" proteins on the cell's surface that are called
"receptors". The most important family of cell-surface receptors transmit their message to the inside of the cell by
coupling to yet another type of protein known as a " G protein", and are therefore commonly referred to as G
protein-coupled receptors (or GPCRs). The current proposal focuses on a special family of GPCRs that mediate
the actions of the neurochemical, serotonin (or "5HT"), in the human brain. These serotonin GPCRs are major
targets for antidepressant and antipsychotic medications, and also play a role in anxiety, migraine and the control
of appetite. Despite the important role of serotonin GPCRs in health and disease, the mechanism of action of many
drugs acting on these receptors remain unknown. Our project will specifically investigate novel molecular
mechanisms associated with serotonin GPCR activity that may prove vital in understanding mechanisms of
psychiatric illnesses, and how many psychiatric medicines actually work.
Research achievements (from final report):
This project has provided new insights into the function of an important family of receptor protiens, namely the
5HT2C receptors, which are targets for the widespread neurochemical, serotonin, as well as many psychotropic
medications on the market. We have identified that different forms of this protein can respond differently to drugs,
as well as being able to interact with one another, which has significant implications for drug discovery targeting
mental illnesses.
Expected future outcomes:
New approaches to targeting 5HT2c receptors.
Name of contact:
Email of contact:
Arthur Christopoulos
arthur.christopoulos@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
400134
Prof Arthur Christopoulos
Basic Pharmacology
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$498,750.00
Standard Project Grant
Title of research award: Allosteric regulation of G protein-coupled receptors.
Lay Description (from application):
The normal function of all living cells depends on how they respond to the multitude of physical and chemical
stimuli to which they are constantly exposed. The majority of these stimuli acting on cells do so not by directly
entering the cells, but rather by acting on specific types of "receiver" proteins on the cell's surface that are called
"receptors". The most important family of cell-surface receptors transmit their message to the inside of the cell by
coupling to yet another type of protein known as a " G protein", and are therefore commonly referred to as G
protein-coupled receptors (or GPCRs). Aberrations in the normal function of these GPCRs have been implicated
in a wide variety of disorders, including neuropsychiatric conditions, endocrine disorders, cardiovascular disease
and many cancers. To date, the majority of drugs acting at GPCRs do so by binding to specific regions on these
receptors. Although many breakthroughs in disease treatment have been achieved using this approach, there
remain a number of acknowledged limitations, including lack of drug selectivity, toxicity and reduced
responsiveness with prolonged therapy. Our current proposal focuses on targeting drugs to alternative regions of
GPCRs that may overcome many of the limitations associated with current drug therapies. An understanding of
the properties of these alternative drug binding sites, which will be investigated in our current grant, can lead to
more effective treatments for a variety of diseases.
Research achievements (from final report):
This project has validated a new approach towards achieving greater selectivity in the actions of drugs, namely, by
targeting novel sites (called "allosteric sites") on the body's receptor proteins at which the majority of drugs act.
As a consequence of our studies, we have discovered novel allosteric small molecules that can lead to superior
treatments for diseases such as schizophrenia and neuropathic pain. In addition, we have developed methods for
quantifying the actions of allosteric drugs, which may find substantial utility in the pharmaceutical industry.
Finally, by combining our small molecules and analytical methods, we have also gained new insights into basic
mechanisms governing drug action at the molecular level.
Expected future outcomes:
A key outcome will be an uptake of our approaches in industry and the subsequent discovery of more selective
drugs.
Name of contact:
Email of contact:
Prof. Arthur Christopoulos
arthur.christopoulos@med.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
284283
Prof Jeff R Richardson
Health Economics
Monash University
Start Year:
End Year:
Total funding:
Grant Type:
2004
2009
$529,650.00
Standard Project Grant
Title of research award: The construction and validation of the Assessment of Mental Health Related Quality of
Life (PsyQoL) instrument
Lay Description (from application):
Mental Health is one of the national health priority areas as well as one of the largest contributors to burden of
disease. WHO projections suggest that by 2020 the burden of depression alone will be second only to
cardiovascular disease. New treatments for mental disorders are being developed which must be evaluated.
Current research methods do not allow an accurate comparison of the cost effectiveness of these therapies with the
cost effectiveness of other medical services as this requires the measurement of 'utility' or 'quality of life'. The
small number of 'generic' 'quality of life instruments' developed to date vary significantly in their 'sensitivity' to
different illnesses-their ability to detect change-and none is very sensitive to changes in mental health states. The
present project is to overcome this deficit. This will be achieved by refining and expanding an instrument
developed in Australia, the Assessment of Quality of Life (AQoL) instrument. This is the only instrument to date
which was both constructed using correct psychometric principles of instrument construction and which describes
health states in terms of the effect upon a patient's ability to function in a social environment. The new instrument
called the PsyQoL will increase instrument sensitivity by including a mental health 'module' to the existing
instrument and revising existing items. The methods used will include several methodological innovations in the
description of health states and the derivation of utility scores. The project will include a large scale 'validation'
study which will include the construction of population 'norms' and also the creation of 'exchange rates' between
the PsyQoL and other instrument scores. The significance of the project is that the PsyQoL will allow valid and
reliable measurement of health states in a way that creates a 'level playing field' between mental and other health
related interventions.
Research achievements (from final report):
The project created the largest multi attribute, quality of life instrument to date. It has been constructed to capture
nuances in the psychological and psycho-psychological dimensions of wellbeing. Psychometric analysis indicates
a high degree of internal validity and preliminary studies indicate its applicability to a wide range of conditions
incuding those outside the narrowly defined psychological domains. The 1250 interviews resulted in a database
which will permit the construction of alternative systems of weights for comparative purposes and transformations
between these metrics. To validate PsyQoL the instrument has been employed in projects in the fields of
psychosis, depression, adolescents with problems, smoking cessation, obesity and acute psoriases. An AQoL
website has been constructed which provides background to MAU instruments, a user manual, the instruments and
scoring algorithms free of charge. Ongoing work will allow the transformation of PsyQoL to equivalent
aproximate values on other MAU instruments. Transformations between AQoL 4D and 6D are complete. The
project budget did not allow for final collection and analysis of utility scores. At July 2009 all data had been
collected and utility algorithms partially completed. They will be on-line by the end of 2009.
Expected future outcomes:
Academic publications have been delayed by the immensity of the data collection. Papers in train include the
instrument psychometrics; data collection; construction of utility algorithms; overview and use. Subsequent
publications will be forthcoming with clinical partners. Methodological papers relating to alternative metrics and
transformations will be published.
Name of contact:
Email of contact:
Professor Jeff Richardson
Jeff.richardson@buseco.monash.edu.au
NHMRC Research Achievements - SUMMARY
Murdoch Childrens Research Institute
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
149222
Prof John W Toumbourou
Mental Health
Murdoch Childrens Research Institute
Start Year:
End Year:
Total funding:
Grant Type:
2001
2001
$55,000.00
Standard Project Grant
Title of research award: Trajectories between childhood internalising behaviour problems and adolescent
depressive symptoms.
Lay Description (from application):
Depressive symptoms are known to escalate sharply through the adolescent years. Adolescents who experience an
episode of depression are very likely to experience further mental illness as adults. Efforts to prevent depressive
illness may be advanced by research delineating the factors and processes implicated in the early emergence of
depressive symptoms. To advance such an understanding this project will analyse data collected, in part, through
NHMRC support to Australian Temperament Project (ATP) researchers. The ATP data will be used to examine
factors associated with the development and progression of depressive symptoms from childhood to adolescence.
The ATP data set includes detailed longitudinal data collected from multiple sources (parents, teachers and youth)
concerning child and adolescent temperament, behavioural problems, mother-child relations, health, depressive
symptoms, school achievement, school adjustment, social skills, peer relationships, parenting practices, stressful
life events, and sociodemographic factors. Of an original sample of 2443 enrolled in the cohort in 1983 (aged 4-8
months) a subsample of 1,350 adolescents should complete the data collection due in 2000 (age 17-18). Through
the analysis of ATP data proposed in this application, models will be developed to explain the risk and resiliency
processes in childhood and early adolescence influencing the development and course of adolescent depression,
for different subgroups of adolescents. To achieve this objective, analyses will: 1. identify groups who have
differing trajectories from childhood internalising behaviour problems to adolescent depressive symptoms; 2.
compare groups to identify factors that contribute to the progression from internalising behaviour problems to
depressive symptoms, while also identifying factors which appear to impede such progression and; 3. compare
groups to identify factors associated with transient versus persistent depressive symptoms in adolescence.
Research achievements (from final report):
Depressive symptoms are known to escalate sharply through the adolescent years. Adolescents who experience an
episode of depression are very likely to experience further mental illness as adults. Efforts to prevent depressive
illness can be advanced by research that can improve our understanding of the factors implicated in the early
emergence of depressive symptoms. To advance such an understanding this project analysed data from the
Australian Temperament Project (ATP), a study that has followed-up through adolescence a cohort of 2,500
Australian children since their birth in 1984. Analyses found that six sub-groups were identifiable on the basis of
differences in their parents’ reports of internalising behaviour problems (e.g., tendency to crying, fearfulness and
anxiety) through the childhood years. Higher levels of internalising problems in childhood were found to predict
depressive symptoms in adolescence, after controlling for other influences. The findings suggest the possibility
that initially high levels of internalising problems can be reduced during childhood. An important implication of
this study is that efforts to prevent adolescent depression could be facilitated through early intervention programs
involving families where parents identify their children to have high levels of internalising problems.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
384419
A/Pr Alasdair L Vance
Paediatrics
Murdoch Childrens Research Institute
Start Year:
End Year:
Total funding:
Grant Type:
2006
2006
$92,000.00
Standard Project Grant
Title of research award: Frontal-parietal-striatal activation in children with ADHD: an fMRI study
Lay Description (from application):
Attention Deficit Hyperactivity Disorder, combined type (ADHD-CT) is a common neuropsychiatric disorder that
has serious consequences for affected children's educational and social development and success in later life.
Despite a large investment in research investigating aetiology and therapeutic strategies that arise from these
aetiological investigations, ADHD-CT remains poorly understood and it is often viewed with therapeutic
pessimism. Understanding the neurobiological basis of ADHD-CT is of tremendous importance for the
development of more specific and targeted medication and/or psychological treatments and, ultimately, to obtain
the best clinical outcome for individual children with ADHD-CT. We have previously examined the function of
frontal-striatal-parietal brain networks in adolescent boys with ADHD-CT, showing dysfunction of brain systems
important for the control of visuospatial attention. In this project, we aim to examine whether these changes in
frontal-striatal-parietal brain function also occur in pre-pubertal 8-12 year-old boys with ADHD-CT. This is
important for two major reasons: Firstly, adolescents and young adults examined in previous brain imaging studies
of ADHD-CT, including our own, are not truly representative of the core of the disorder, as ADHD-CT has its
peak prevalence from 8 to 12 years of age. Secondly, by now comparing pre-pubertal ADHD-CT and healthy
control children we can determine whether the changes in brain function we have previously identified represent
developmental stage independent brain dysfunction that is characteristic of ADHD-CT.
Research achievements (from final report):
This study is the first to explicitly identify the contribution of the parietal lobe to spatial attentional and working
memory deficits in pre-pubertal children with ADHD. It builds upon our previous work defining a similar
contribution in adolescents with ADHD. Hence, these results suggest that impaired frontal-parietal-striatal
function is a developmental stage independent finding in ADHD. This work was published in the world leading
biological psychiatry journal, Molecular Psychiatry.
Expected future outcomes:
This research will aid the development of more specific biological markers for ADHD and for stimulant
medication treatment response in ADHD.
Name of contact:
Email of contact:
Professor Alasdair Vance
avance@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
334325
Prof George C Patton
Epidemiology
Murdoch Childrens Research Institute
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$495,575.00
Standard Project Grant
Title of research award: Young adult social transitions-Course of mental and behavioural disorders: The
Victorian Adolescent Health Cohort Study.
Lay Description (from application):
The paths young people follow into adulthood have changed markedly in the past three decades. Traditionally the
adoption of a role as marital partner, parent and fulltime employee in the late teens and early twenties was
accompanied by a diminution or 'maturing out' of health risk behaviours and emotional problems arising in
adolescence. The social transitions into adulthood are now both delayed and in many instances changed with
higher rates of cohabitation, extended teriary educational participation and part-time employment. The effect of
these social changes on health risk behaviours, behavioural and mental disorders is uncertain. This proposal will
undertake a further follow-up in the late twenties of a group of just under 2000 young Victorians, already studied
from the age of 14 years through to the age of 24 years. This study will assess the persistence of behavioural
problems such as smoking and nicotine dependence, excessive alcohol consumption and dependence, cannabis
dependence, illicit drug use, risk sexual behaviour, depression and anxiety disorders. The extent to which these
may be associated with successful negotiation of transitions in education, employment, relationships, parenthood
and establishing an independent home will be evaluated. Alternative explanations including the severity of
dependence syndrome, personality, social background and genetic risk factors will also be explored.
Research achievements (from final report):
The successful completion of the ninth wave of data collection has opened the way for understanding of the
natural history of common adolescent health problems across the transition to adulthood and the effect of these
problems on those transition into marriage, employment and parenthood so central to healthy adjustment for the
individual and his/her children. In the end we managed to complete 1521 interviews. This compares favourably
with the 1520 interviews at wave 8 and 1603, at wave 7. The study provides an epidemiological basis for planning
prevention and early intervention work with adolescents and young adults. Recent publications have considered
questions of relevance to policy eg what are the safe levels and patterns of of alcohol use in adolescents and
practice eg what are the longer term health and life outcomes of eating disorders in adolescents and where should
the clinician focus his or her efforts?
Expected future outcomes:
We will continue to publish from this data set across a wide range of areas. At present we have plans to publish
around the consequence of early pregancy including termination of pregnancy, adolescent cannabis use,
adolescent alcohol use, self-harm, and common mental disorders.
Name of contact:
Email of contact:
Prof George Patton
george.patton@mcri.edu.au
NHMRC Research Achievements - SUMMARY
Queensland Institute of Medical Research
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
241916
Dr Dale R Nyholt
Neurogenetics
Queensland Institute of Medical Research
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$530,000.00
Standard Project Grant
Title of research award: Genetic analysis of migraine and comorbid psychiatric disorders using twin families
Lay Description (from application):
Typical migraine, is a frequent, debilitating and painful disorder that normally affects people during their most
productive years (up to 25% of females and 7.5% of males in Western populations). Additionally, several studies
have demonstrated a cross-sectional relation between psychiatric disorders (namely anxiety and depression) and
migraine in community samples. The World Health Organization (WHO) recently identified migraine and major
depression among the world's top 20 leading causes of disability, with an impact that extends far past the suffering
individual, to the family and community. In both sexes of all ages, depression and migraine are the 1st and 19th
leading causes of disability affected life years. Although both migraine and depression are highly prevalent in our
society, their aetiologies remain relatively obscure and there are no laboratory based diagnostic tests that identify
those who suffer from the disorders. Because so little is known about them, a positional cloning approach is the
only feasible way to identify the molecular mechanisms underlying these disorders.This project will collect a
sample with sufficient power to perform a genome wide linkage screen to i) identify novel susceptibility genes,
and ii) confirm previously reported susceptibility genes for migraine and co-occurring psychiatric disorders. The
susceptibility genes identified (and confirmed) in this sample will provide clues to the further elucidation of the
complex molecular pathways of migraine (and co-occurring psychiatric disorders) and, finally, will help in the
development of diagnostic tests and rational treatment strategies.
Research achievements (from final report):
The primary objective of the funded project concerned the collection of DNA samples, to provide an extremely
valuable and powerful resource enabling the genetic dissection of migraine and comorbid psychiatric disorders
[via linkage and association studies]. Progress in achieving the research aims and in testing hypotheses: 1)
Publication entitled "Latent class analysis does not support migraine with aura and migraine without aura as
separate entities" (associated publication #2). Work is continuing on univariate (associated publication #1 & #6)
and multivariate genetic analysis of migraine symptoms [results indicate all 10 of the International Headache
Society (IHS) migraine symptoms are heritable]. The resulting phenotypes lead to improved power & lead to
important publications (associated publication #3-5). 2) 2300 DNA samples have been collected from >400
migraine families. Updated and extended migraine symptom data has also been collected for these individuals. 3)
A subset of these families (751 individuals) was recently genotyped for genome-wide linkage through my
collaboration with Aarno Palotie and Leena Peltonen as part of the GenomeEUtwin consortium. 4) Attracted
funding from the NHLBI Mammalian Genotyping Service (USA): "Mapping genes for typical migraine using
twin families". CIA: Nyholt DR, CIB: Montgomery GW. To perform a genome-wide linkage scan [400
marker/10cM resolution] for 1790 individuals. 5) Attracted funding from NHMRC to test candidate genes, within
two regions showing significant linkage, for association with migraine. Results provide narrow defined regions in
which to search for specific genes contributing towards migraine susceptibility. Identification of such genes will
provide clues to the further elucidation of the complex molecular pathways of migraine and, finally, will help in
the development of diagnostic tests and rational treatment strategies.
Expected future outcomes:
Eventual identification of migraine susceptibilty genes; which will provide clues to the further elucidation of the
complex molecular pathways of migraine and, finally, will help in the development of diagnostic tests and rational
treatment strategies
Name of contact:
Email of contact:
Dr Dale R. Nyholt
daleN@qimr.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
339450
Prof Nicholas G Martin
Quantitative Genetics
Queensland Institute of Medical Research
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$751,200.00
Standard Project Grant
Title of research award: Mapping genes for anxiety and depression
Lay Description (from application):
High scorers on the personality trait neuroticism are at greatly increased risk of major depression and other
neurotic disorders. Neuroticism is a personality trait that shows considerable stability over adulthood. It has a
strong genetic basis and it seems that the same genes also determine risk of depression, anxiety and other
neuroses. By selecting twins and sibs extremely discordant and concordant (EDAC) for neuroticism we can
greatly reduce the cost and increase the power to find genes influencing depression. Questionnaire responses and
interviews from 15,027 Australian twins and 11,389 of their family members were reviewed to identify
individuals with neuroticism scores in the top and bottom 10%. These individuals were invited to participate in a
structured psychiatric interview by telephone, and to give a blood sample. Participation and DNA sampling rates
were high and there was minimal evident participation bias. DNA was collected from 2,926 individuals from 884
families including 1,333 EDAC sibling pairs and over 795 parents. A preliminary genome scan on one third of this
sample yields several linkage peaks suggesting genes of major effect that appear to replicate findings in similar
studies conducted in Holland and England. Given these results it is highly desirable that we obtain a genome scan
on the remainder of selected extreme sample. Another one third of this sample is currently being genotyped in
America and here we request funds to genotype the remaining third. .If we are successful in identifying genes
underlying neuroticism, we will also be able to analyse their contribution to depression and anxiety. This could
lead to better drug treatments.
Research achievements (from final report):
Created a key resource for GWAS for depression and was instrumental in discovery of PCLO as a possible
depression gene.
Expected future outcomes:
If the PCLO gene is further confirmed for depression, it will be the first solid finding for this disease and will
suggest new targets for therapeutics
Name of contact:
Email of contact:
Professor Nicholas Martin
Nick.Martin@qimr.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
339454
A/Pr Bryan J Mowry
Psychiatry
Queensland Institute of Medical Research
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$500,000.00
Standard Project Grant
Title of research award: A genome-wide linkage study of schizophrenia in a large sample from Tamil Nadu,
India
Lay Description (from application):
A Study of Schizophrenia in Tamil Nadu, India. The cause of schizophrenia is unknown, but there is good
evidence that genes play a role. Geneticists do not fully understand how the disease is inherited, but it is very
complex, and several interacting genes as well as environmental factors are probably involved. We have been
recruiting families with at least two siblings with schizophrenia from a number of communities/casts in Tamil
Nadu. We plan to recruit a total of 400 affected sibling families, together with 400 trio families (both parents, plus
their affected child). A genome-wide scan of the genetic code in all individuals will be conducted to identify
chromosomal regions linked to schizophrenia. This is the first necessary step toward identifying schizophrenia
susceptibility genes. If one or more genes are discovered, this will greatly improve our understanding of this
disease. It will also stimulate the search for similar genes in other samples world-wide, including Australia where
schizophrenia costs $2.5 billion annually in terms of treatment and loss of employment. With such a discovery, it
may be possible to find better treatments that correct the basic cause of the illness and identify factors that protect
against the illness.
Research achievements (from final report):
We have been recruiting families with at least two siblings with schizophrenia from a number of
communities/castes in Tamil Nadu, India. We recruited 124 affected sibling families. A genome-wide scan of the
genetic code in all individuals was conducted to identify chromosomal regions linked to schizophrenia. We
detected a new region significantly linked to schizophrenia on the short arm of chromosome 1 (region 1p31.1).
This is the first necessary step toward identifying schizophrenia susceptibility genes. If one or more genes are
discovered in this region, this will greatly improve our understanding of this disease. It will also stimulate the
search for similar genes in other samples world-wide, including Australia, where schizophrenia costs $2.5 billion
annually in terms of treatment and loss of employment. With such a discovery, it may be possible to find better
treatments that correct the basic cause of the illness and identify factors that protect against the illness.
Expected future outcomes:
We are testing the generalisability of our finding to other ethnic groups, and have conducted fine mapping
experiments to further investigate this finding. Most recently we have conducted a genomewide association study
to identify causative variants in identified regions of association. It is hoped this research will eventually lead to
the identification of susceptibility genes.
Name of contact:
Email of contact:
Professor Bryan Mowry
bryan_mowry@qcmhr.uq.edu.au
NHMRC Research Achievements - SUMMARY
St. Vincent's Institute of Medical Research
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
247901
Prof Michael W Parker
Membrane Biology
St. Vincent's Institute of Medical Research
Start Year:
End Year:
Total funding:
Grant Type:
2003
2007
$800,000.00
Standard Project Grant
Title of research award: Structural studies of the GABA receptor
Lay Description (from application):
This proposal concerns the biochemical investigation of a protein called GABA receptor which is a known target
for various anti-anxiety drugs (anxiolytics), anti-convulsants, sedatives, depressants, anti-epilespy drugs, alcohol
and anaesthetics. This work is expected to lead to the determination of the three-dimensional shape of the protein
which will provide essential information about how the protein works and lay the foundation for the design and
development of new drugs to control epilepsy, act as general anaesthetics, relieve anxiety and induce sleep.
Research achievements (from final report):
We have gained crucial insights into how a receptor in the brain is regulated by a range of chemicals. This
receptor, called the GABA receptor, is the the target for many commonly used drugs to treat mental disorders
including anti-anxiety drugs, sedatives, depressants, anaesthetics and anti-epilepsy drugs.
Expected future outcomes:
We expect our work will eventually lead to new drugs to treat anxiety and epilepsy without the side-effects of
currently available drugs.
Name of contact:
Email of contact:
Professor Michael Parker
mparker@svi.edu.au
NHMRC Research Achievements - SUMMARY
The Children's Hospital at Westmead
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
3508
A/Pr Thiagarajan Sitharthan
Epidemiology
The Children's Hospital at Westmead
Start Year:
2000
End Year:
2003
Total funding: $181,518.00
Grant Type: NIDS Project - National Illicit
Drugs Strategy 26
Title of research award: An evaluation of a community-based opportunistic intervention to reduce substance
abuse among psychiatric patients
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Alcohol and other substance misuse are very common among psychiatric patients and poses major management
problems. However, both drug and alcohol and mental health specialists have long recognised that neither service
provided adequate care for such "comorbid / dual diagnoses" patients. Provision of an opportunistic integrated
intervention was seen as a useful option in managing such patients. To explore the scope of such an intervention,
this study screened all psychiatric patients for alcohol and other substance use and those who were eligible were
provided with psychological treatment to reduce their substance use /alcohol intake and the problems associated
with such use. By implementing this trial in the community, we were in an an ideal position to train mental health
staff and General Practitioners, to screen for alcohol/substance misuse and mental health problems - and refer
suitable subjects to the study. In addition, preliminary results suggest that the cognitive-behavioural psychological
treatment was effective in reducing substance / alcohol use and associated problems. Screening instruments and
treatment training manuals have been developed and are currently used to train the mental health and drug and
alcohol workforce.
Expected future outcomes:
We expect (i) the formation of collaborative partnerships between D&A and mental health agencies, (ii) the
workforce to be easily trained to deliver an intervention that is both time-limited and relatively inexpensive, and
(iii) the development of a framework to conduct service evaluations.
Name of contact:
Email of contact:
A/Prof Thiagarajan Sitharthan
thiagarajan_sitharthan@wsahs.nsw.gov.au
NHMRC Research Achievements - SUMMARY
Turning Point Alcohol and Drug Centre
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
116203
Start Year:
Dr Greg R Rumbold
End Year:
Public Health and Health Services not elsewhere classified
Turning Point Alcohol and Drug Centre
Grant Type:
2000
2001
Total funding: $189,106.16
Standard Project Grant
Title of research award: A investigation of the public health effects of retail heroin markets from a consumer
perspective
Lay Description (from application):
The health problems associated with heroin use within our community are a major public health issue. Within the
past decade there has been an increase in heroin-related deaths and evidence of the continuing spread of hepatitis
C among individuals who inject heroin. Within this period there have been substantial changes in the heroin
market in Australia, with street prices decreasing and purity increasing and we have witnessed the emergence of
street markets in a number of major cities. The aim of the proposed research is to improve our understanding of
the retail heroin market (that part of the market which is accessed by heroin users) by examining how the
consumers (heroin users) use this market. The project will examine the relationship between the heroin market and
the health problems associated with heroin use including dependence. The research will be conducted at 6 sites
within metropolitan Melbourne which have been chosen on the basis that they have established street markets and
high levels of non-fatal and fatal overdose. At each site interviews and surveys will be conducted with injecting
drug users and others with knowledge of the local market and detailed observations will be made of street markets
in each of these areas. This information will be combined with indicators of purity of heroin seized by police, fatal
and non fatal-overdoses, police operations and arrests, and needle/syringe distribution and return. The information
gathered in this research will be used to develop an understanding of the retail heroin market as a consumer
market place and the impact of the market upon the health status of the individuals who use this market. The
knowledge that we gain from this research will provide the foundation for developing more effective approaches
to reducing the health problems associated with heroin use and for predicting the impact of changes in the market
such as a reduction in price upon these problems.
Research achievements (from final report):
Much of the data collected over the course of the research remains to be analysed and published. The information
gathered in this research will be used to further develop our understanding of street-level illicit drug markets, the
dynamics of those markets and the impact of street-level drug markets upon the health status of individuals who
participate in them. The knowledge gained may be used to provide the foundation for developing more effective
approaches to reducing the health problems associated with street-level drug markets and for predicting the impact
of changes in the market upon these problems. In-depth ethnographic investigation of one of the six primary
street-level illicit drug markets in Melbourne continues with PhD research currently being conducted by the
Research Officer who was employed on the present study. The combination of these two sets of data provides us
with four years of observational data with which to analyse the dynamics of the retail heroin market in Melbourne
and its implications for public health.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
University of Adelaide
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
157905
Dr Rodney J Irvine
Pharmacology not elsewhere classified
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$180,000.00
Standard Project Grant
Title of research award: MDMA -induced neurotoxicity
Lay Description (from application):
The use of "ecstasy" and similar stimulant drugs is increasing in Australia and globally. "Ecstasy" can cause death
within hours of ingestion but this occurs only in a small number of users. In contrast, there is recent compelling
evidence that a large proportion of users of this drug develop significant and irreversible brain damage due to its
use. This latter toxicity is insidious in that it may not become evident to users as impaired brain function until
years after their drug use. As a result of the emerging scientific evidence, The National Institute of Drug Abuse in
the USA has recognised the major adverse health impact of these drugs in a recent inititative. The brain has a
blood brain barrier to stop toxic substances entering, but we postulate that this is damaged by the immediate
effects of "ecstasy". This allows acces of toxic breakdown products from the drug to enter the brain and cause the
long term damage. If we understand the biological mechanisms which link the immediate and long term effects of
"ecstasy", we should be in a position to design strategies or therapies which limit its harmful effects. The purpose
of this project is to 1. establish if the blood brain barrier is damaged by "ecstasy" 2. identify environmental factors
which contribute to the severity of the toxic effects. We believe that an understanding of these events and the
development of evidence based rational treatments for these toxicities is essential: 1 in the short term, to prevent
injury and death from these drugs,and 2 in the long term, to prevent a potential major public health problem from
neurodegenerative deficits that may be magnified as users age. We believe that our group has the ideal mix of
expertise and state of the art methods to make a significant advance in the understanding these problems.
Research achievements (from final report):
Australia has the highest per capita use of 'ecstasy' (MDMA) in the world. The health outcomes to the nation and
to individuals are not clear but are likely to be substantial as use can lead to a number of severe physical and
mental problems. Our project was an attempt to better understand how these drugs work in order that preventative
strategies can be improved and useful interventions designed. We undertook preclinical work which identified a
possible new cellular target for the treatment of 'ecstasy" overdose and we also undertook some pilot work on
ecstasy users which identified alarming variations in the blood concetrations of these drugs in recreational users.
This latter finding may explain some of the severe adverse effects and is the subject of continuing research.
Expected future outcomes:
Identification of the circumstances that lead to adverse effects of 'ecstasy' such as overheating, cardiovascular
stimulation, anxiety and depression.
Name of contact:
Email of contact:
Rod Irvine
rod.irvine@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
157942
Prof Andrew A Somogyi
Pharmacology not elsewhere classified
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$196,527.54
Standard Project Grant
Title of research award: Distribution kinetics of opioids used in substitution programs
Lay Description (from application):
Heroin addiction is a major national and international problem costing hundreds of millons of dollars to Australia
alone. The major form of treatment is methadone taken as maintenance treatment once a day. While methadone is
effective in most addicts, about one third of them complain that it does not last long enough and they either
tolerate this inadequate form of treatment or are prescribed a newer drug as part of a clinical trial or drop out and
revert to heroin. We have previously shown that the blood levels of methadone are important in determining its
best use and specifically, that those addicts for whom methadone does not hold have a greater drop in their blood
levels after methadone has been absorbed into the body. This drop in blood levels is mainly due to methadone's
redistribution throughout the body. Very little is known about how methadone distributes and redistributes
throughout the body but it appears that the lung is the most important organ. A number of questions need to be
answered to improve methadone's use: 1. How quickly is methadone taken up into the lung compared to the brain;
2. Why is the lung able to take up and release a large amount of methadone; 3. How does decreased respiration
influence the lung and brain uptake of methadone; 4. What happens when another drug is prescribed (such as an
antidepressant) which reduces the lung uptake of methadone; 5. Do some of the newer drugs for heroin addiction
have better lung distribution and binding properties. We will perform studies of the concentrations of methadone
and newer drugs in sheep that will provide the scientific basis for answering these questions and permit better use
of drug treatment for heroin addiction.
Research achievements (from final report):
Methadone is an opioid analgesic that acts in the brain. It also has an important role in substitution programs for
heroin addicts, where oral doses are given once or twice a day in place of heroin. The administration of methadone
in these programs is not without risk. While doses must be individualized for each patient, there is variability in
each patient's response to their dose that can produce adverse events such as sedation, respiratory depression and
occasionally death. There has been on-going work seeking to understand this variability, but it has focussed on
measuring the amount of methadone in blood. For the first time, this project investigated in animals how the
movement of methadone from the blood into the brain contributes to this variability in response. We found that a
common side effect of methadone, respiratory depression, and actually increases the amount of methadone in the
brain, potentially leading to further respiratory depression. An important outcome is the need for a reappraisal of
the effect of respiratory depression on methadone doses and effects in these patients. Future directions include
testing this theory in the patients themselves, with the hope of identifying those at risk of methadone toxicity by
this mechanism.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
207710
Prof Jason M White
Clinical Pharmacology and Therapeutics
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$420,000.00
Standard Project Grant
Title of research award: Clinical Pharmacology of Methadone during Induction onto Maintenance Treatment
Lay Description (from application):
Heroin addiction can be very successfully treated by substituting heroin with methadone. The transition of
stopping heroin and starting methadone is risky and can be associated with death. This application seeks to
explore the mechanisms of the increased risk during this transition period so that appropriate management
strategies might be instituted.
Research achievements (from final report):
Heroin addiction can be successfully treated using methadone maintenance. However, the transition from heroin
use to methadone is associated with deaths due to depressed breathing. This study was designed to improve our
understanding of how concentrations of methadone in the body change during this induction phase and the effects
of these varying concentrations. The research has clearly demonstrated variability in the dosage requirements for
different individuals and the differences in response to methadone. In some individuals there are significant
adverse effects that are potentially life threatening and we need to be able to predict who these people are. Our
results have shown a long held theory that methadone was eliminated faster in the body the longer a person was
exposed to the drug is not true. We were able to show that a test that was expected to predict this variability in
response to methadone was not able to do so. This points to the next strategy that can be used and that is to
measure blood concentrations at 2 different points in time and then to use a mathematical model to predict
concentration. Our research has therefore been able to describe why the difficulties arise in the initial phase of
methadone and its treatment and to point to the way in which the individuals at risk can best be predicted.
Expected future outcomes:
The next phase of this research will be to put into practice the methods that have been suggested for predicting
response to methadone treatment based on the results of this study. This is currently being done in clinics and it is
expected that this will improve the quality of methadone maintenance treatment.
Name of contact:
Email of contact:
Jason White
jason.white@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
207780
Prof Michael G Sawyer
Mental Health
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$113,160.00
Standard Project Grant
Title of research award: Parenting style as a mediator of psychosocial risk factors and childhood behaviour
problems.
Lay Description (from application):
It is imperative that effective interventions be developed and evaluated for children with externalising disorders
(e.g. oppositional disorder, attention deficit order and conduct disorder). The prevalence of these problems in the
community is high, the prognosis of children is poor, and externalising problems are passed on across successive
generations in the same family. Childhood externalising problems are also one of the most costly behavioural
disorders for society. Many studies have examined the nature and course of externalising problems in older
children and adolescents. However, little attention has been paid to the early onset of externalising disorders
amongst preschool and early school-age children. Whilst the relationships between family risk factors (e.g. marital
discord and maternal depression), parental management styles and children's behaviour problems are widely
recognised, the exact nature and direction of these relationships remains largely unknown. This proposal will
provide new information about the mechanism through which family risk factors such as marital discord or
parental distress influence the onset and persistence of externalising problems in young children, via their effects
on parents' behaviour management techniques. This information can then be used to instruct early intervention
efforts for parents and families of children at risk of developing externalising behaviour problems.
Research achievements (from final report):
It is imperative that effective interventions be developed and evaluated for children with externalising disorders
(conduct disorder, oppositional disorder, attention deficit disorder). The prevalence of these problems in the
community is high, the long-term outcome for these children is poor, and externalising disorders are one of the
most costly behavioural disorders for society. This study paid much-needed attention to the early onset of
externalising behaviour problems amongst preschool and early school-age children. A group of 4-year-old
children were followed till age 6 to identify risk factors for early childhood externalising problems. It was found
that children with significant externalising behaviour problems at age 6 tended to have a high level of
externalising behaviour at age 4, were more likely to be male, and on average exhibited a more inflexible
temperament and had experienced greater exposure to over-reactive parenting practices (yelling, physical
punishment, insults). Further, increases over time in inflexible temperament and over-reactive parenting were also
predictive of externalising behaviour problems at age 6. This information on risk factors for externalising
problems in young children can be used to instruct early intervention efforts for parents and families of children at
risk of developing externalising behaviour problems. Early interventions aimed at improving parenting parctices
and temperament may be effective in decreasing the prevalence of early childhood externalising behaviour
problems.
Expected future outcomes:
Accurate early detection of children with potentially persistent externalising problems means it is possible to
target early intervention programs which improve parent management practices and children's temperament.
Following this study further research is being undertaken exploring mental health resilience in pre-school
children.
Name of contact:
Email of contact:
Professor Michael Sawyer
michael.sawyer@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
207813
Prof Alexander C McFarlane
Psychiatry
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$290,000.00
Standard Project Grant
Title of research award: Adult Consequences of Childhood Exposure to Psychological Trauma
Lay Description (from application):
The importance of childhood experience to adult adjustment (DOES THIS MAKE SENSE) is an issue of general
public health interest. In particular, in the area of personality development, there are a number of theories
concerning the importance of childhood experience and developmental stresses on later personality, development,
psychological functioning and physical health. More recently there has been debate on the accuracy with which
adults areable to remember traumatic experiences in childhood. This study will follow a group of 808 primary
school children who were exposed to the 1983 Ash Wednesday bushfires in SOuth Australia. They were involved
in a study which examined them two months, eight months and twenty six months after the disaster. This rich
descriptive set of information about these children and their families forms an objective data base against which
their adult recall of the experience can be judged. The symptoms of these children were also documented at the
time as was their disaster exposure. The impact of this one event, in the context of the other developmental
influences will be examined as determinants of their adjustment in adult life. Finally, there has been an increasing
interest in the way that previous traumatic exposure influences the nature of the hormonal response to stress.
Using a test of functioning of the cortisol system, the stress response of this population will be compared with a
control population who were also studied at the time of the original disaster.
Research achievements (from final report):
This study is the largest study published to date examining adult psychopathology following disaster exposure in
childhood. A representative sample of 806 Australian adults exposed to the Ash Wednesday Bushfires in South
Australia as children in 1983 and 725 matched control subjects recruited at the time of the initial study were
followed up 20 years post-disaster. In total 67% (N=540) of the bushfire survivors and 65% (N=471) of controls
participated in the study. Results demonstrated that whilst exposure to a major disaster in childhood by itself did
not significantly increase the rates of adult psychopathology other than specific phobia, it significantly increased
the risk of developing a spectrum of psychiatric disorders on subsequent trauma exposure in this population.
Bushfire survivors were also at a significantly increased of a number of health risk behaviours such as cigarette
smoking, alcohol consumption and illicit drug use and had a higher prevalence of rape than those who had not
been exposed to the bushfire. Overall findings from this study emphasizes the nessessity to account for the
accumulating burden of trauma exposure in all longitudinal studies examining adult psychiatric outcomes of
trauma exposure in childhood and the need to follow cohorts beyond adolescence.
Expected future outcomes:
Results from this study challenge pre-conceptions about the relationship of trauma to a range of adult psychiatric
disorders and should alter the way longitudinal trauma research is conducted. Further follow-ups on this sample
will assisit in delineating this complex relationship between childhood trauma and adult psychopathology.
Name of contact:
Email of contact:
Alexander McFarlane
alexander.mcfarlane@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
299050
Prof Andrew A Somogyi
Clinical Pharmacology and Therapeutics
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$235,500.00
Standard Project Grant
Title of research award: Mu Opioid Receptor Polymorphisms and Variability in Opioid Actions
Lay Description (from application):
The treatment of pain in cancer patients is not optimal nor is the use of substitution therapy in heroin addiction.
What links these two treatments is a group of drugs known as opioids- morphine for pain and methadone for
dependence. People differ substantially in the dose of these two drugs to treat these conditions and the reasons for
such large differences are not known. This application seeks to explore the role of genetic variations in the target
site at which opioids act in explaining why people differ in their response to these medicines. Studies on humans
and cell preparations will allow one to study the basic mechanisms and then translate this into the actual clinical
setting. If successful, the results could mean better dose and medicine selection for people with pain and those
seeking treatment for heroin addiction.
Research achievements (from final report):
We discovered several genes in patients that contribute to the successful use of a drug called methadone which is
used in pain and addiction managements. We also were able to show that a previously reported gene has no impact
because we had better patient description and recording of results.
Expected future outcomes:
We are studying one of the genes to determine whether it improves treatment of alcoholism and a larger study in
patients with pain to try and improve personalised treatment to their chronic pain .
Name of contact:
Email of contact:
Prof Andrew Somogyi
andrew.somogyi@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
250340
A/Pr Jozef Gecz
Neurogenetics
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2002
2007
$548,750.00
NHMRC Research Fellowship
Title of research award: NH&MRC Senior Research Fellowship, SRFB
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
During the course of the research fellowship I have lead national and international effort into gene discovery for
various, heritable forms of intellectual disability and epilepsy. Together with a team of national and international
collaborators we have identified multiple (>20) different genes in which naturally occuring mutations cause
intellectual disdability with (including eg. autism and epilepsy) or without additional features. This work has been
captured in 56 peer reviewed original and review publications. This work has made a significant positive impact
on the families participating in the study (eg. increased their reproductive confidence due to the knowledge of the
causative gene & mutation), contributed to the development of new tests for these forms of intellectual disability
worldwide and paved the way for future development of treatment strategies based on this knownledge. The
genetic heterogeneity underlying different forms of learning disability is considerable and unexpected. Such
genetic heterogeneity (in the absence of other than molecular diagnostic tests) will create additional complexity
and unexpected challenges for future health service delivery for these individuals and their families. The
knowledge of the variety and type of genes causing learning disability is also of enormous benefit for our
understanding of the normal brain function and human cognition.
Expected future outcomes:
Creation of suitable animal models, which will be used for the investigations of possible treatments and/or better
management strategies for these patients.
Name of contact:
Email of contact:
Jozef Gecz
jozef.gecz@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
349485
Dr Rodney J Irvine
Clinical Sciences not elsewhere classified
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$347,300.00
Standard Project Grant
Title of research award: The Effects of MDMA in humans
Lay Description (from application):
Ecstasy use is growing faster throughout the world than than any other drug of abuse. United Nations figures from
2003 show that it is used by more individuals than the combined total of cocaine and heroin users. Australia has
the highest per capita use of 'Ecstasy' in the world with rates twice those of North Americal and Europe. As a
result of this we also have a high rate of adverse effects. These can be immediate, and lead to death, or long term
leading to brain damage and psychopathologies. So far, no studies have been conducted,anywhere in the world,
which have objectively examined the medical effects of 'ecstasy' in the dance clubs where it is used. Because of
this, there is a lot of speculation on whether the animal based or hospital based studies are valid and relate to
normal recreational use of this drug. This has led to a degree of suspicion by users and health professionals as to
the medical problems claimed to be associated with the drug. This project extends a pilot study we undertook
which has highlighted that in a recreational setting it is likely that specific individuals are susceptible to damage
by 'ecstasy'. The purpose of this project is to examine this in detail, and identify who, and why some young
persons are at risk of immediate life threatening outcomes from 'ecstasy' use or may develop brain damage later.
The intended outcome is to provide clear evidence of adverse effects and why they occur. This evidence may be
used to improve harm minimisation and treatment programs.
Research achievements (from final report):
This is the first study of its kind in the world examining the health effects of the recreational use of 'ecstasy' and
similar drugs in a naturalistic setting. We have collected data from over 60 'ecstasy users and have the physical,
biochemical, pharmacodynaamic and pharmacokinetic measures before ingestion and for up to 5 hours at hourly
intervals after ingestion. This is a very significant achievement in that such data is hard to obtain in this type of
participant where objective measures involving repeated blood sampling is required. The data has established
concentration/response relationships for the acute effects of ecstasy and has revealed that the concentrations
achieved by a significant number of ecstasy users have the potential for short and long term harm to their health,
but only where high blood concentrations are achieved. Population pharmacokinetic/pharmacodynamic modeling
which is being undertaken on the data will form the basis for the formulation of guidelines on advice to users and
health authorities on harm minimisation measures.
Expected future outcomes:
The objective nature of the data and its direct relevance to the usual way in which 'ecstasy' is used will provide a
very strong scientific evidence base for future studies on the use of this drug. It will also provide the basis for the
development of harm minimisation policies and programs which will be difficult for users to dismiss as not
relevant to their use of the drug.
Name of contact:
Email of contact:
Rod Irvine
rod.irvine@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
349536
Prof Jason M White
Clinical Sciences not elsewhere classified
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$534,174.00
Standard Project Grant
Title of research award: A trial of therapeutic during monitoring in methadone maintenance treatment
Lay Description (from application):
Heroin addiction is an established and increasing problem in developed countries and in many developing nations.
Although there have been several new treatments for heroin addiction, methadone maintenance remains the most
effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test
a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects
in determining when to increase doses, and when to switch to alternative therapies. This provides an objective
method of planning treatment that focuses on suppressing heroin use. The potential subjects of the study are the
50% of patients who continue to use heroin regularly during treatment. All will undergo assessment involving
measurement of blood levels of methadone, testing of effects and side-effects of methadone, and monitoring of
safety. Half will be randomly allocated to usual care, and half to therapeutic drug monitoring, with dose
adjustments according to the results of testing. At 3 and 6 months all subjects will undergo repeat test sessions. It
is hypothesized that those in the experimental group will be using less heroin (confirmed by hair testing). It is
expected that the study will also identify a small group of subjects with genetically different opioid receptors, who
will require very high doses of methadone to be stabilized. The study will allow a detailed analysis of how best to
monitor dose adequacy; the relationship between withdrawal symptoms, methadone blood levels, and heroin use,
and will provide the first clear investigation of the relationship between changes in methadone blood
concentration and certain potentially dangerous changes in the electrical activity of the heart. The intended
outcome of this research project is a model for a higher standard methadone program that is more effective in
reducing the problems of heroin use in our community.
Research achievements (from final report):
This project was aimed at improving treatment for drug dependence. Specifically, it demonstrated how a more
sophisticated approach to methadone maintenance can make it more effective. Normally methadone doses are
adjusted based on the judgement of the prescriber and the reports of the patient. However, an effective dose is not
easy to achieve as each person is different in how their body responds to the drug. In order to make the decision of
the prescriber better informed, we have used a method whereby the concentration of the active form of
methadone, R-methadone, is measured in every patient and doses are then adjusted so as to achieve target
concentrations that are known to be effective. This method was shown to produce better outcomes than the
conventional approach to dose adjustment. As part of this work we used a method for determining how effective
methadone was in blocking the effects of opioid drugs administered intravenously. This, together with its ability to
prevent the withdrawal syndrome, is the basis of methadone's clinical effectiveness. The study showed that this
blocking effect was more pronounced in those with higher concentrations of the active R-methadone. This further
supports the use of dose determination based on concentrations of R-methadone. In addition, we demonstrated for
the first time an important genetic determinant of response to methadone and lack of influence of another.
Expected future outcomes:
Both this approach to dose adjustment and the use of genetic markers of response could be implemented in
methadone clinics and by private methadone prescribers. While there are additional costs associated with this
more sophisticated approach, it does produce better outcomes. The most efficient use may be in people not
achieving good outcomes with the conventional approach.
Name of contact:
Email of contact:
Jason White
jason.white@adelaide.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
349301
A/Pr Maria Makrides
Clinical Sciences not elsewhere classified
University of Adelaide
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$1,644,000.00
Standard Project Grant
Title of research award: A Randomised Trial of DHA in Pregnancy to Prevent Postnatal Depressive Symptoms
and Enhance Neurodevelopment in Children.
Lay Description (from application):
Postnatal depression strikes 12-17% of women in the year after giving birth. Postnatal depression can result in
emotional, behavioural and developmental problems in children. Although there are many complex psychological
and social factors involved, supplementing the diet with an omega-3 fat called DHA has been shown to alleviate
the symptoms of depression. Enriching diets with DHA has also been associated with improvements in visual and
neural abilities of young infants. Normally, DHA is obtained through the mother's diet and is then passed onto the
developing baby whilst in the womb. However, the amount of DHA that is delivered to the baby in pregnancy is
high, and in most cases is far higher than most Australian mothers get in their diets. In this study we will test
whether supplementing the diets of pregnant women with DHA results in women suffering less depressive
symptoms and children with better development scores. If our study is successful, it will result in a simple and
effective way to prevent postnatal depression and improve the developmental outcome of the children.
Research achievements (from final report):
Postnatal depression strikes 12-17% of women in the year after giving birth. Postnatal depression can result in
emotional, behavioural and developmental problems in children. Although there are many complex psychological
and social factors involved, supplementing the diet with an omega-3 fat called DHA has been shown to alleviate
the symptoms of depression. Enriching diets with DHA has also been associated with improvements in visual and
neural abilities of young infants. Normally, DHA is obtained through the mother's diet and is then passed onto the
developing baby whilst in the womb. However, the amount of DHA that is delivered to the baby in pregnancy is
high, and in most cases is far higher than most Australian mothers get in their diets. In this study we will test
whether supplementing the diets of pregnant women with DHA results in women suffering less depressive
symptoms and children with better development scores. If our study is successful, it will result in a simple and
effective way to prevent postnatal depression and improve the developmental outcome of the children
Expected future outcomes:
Once the results are available, we will be able to provide dietary guidelines for pregnant women that may prevent
symproms of postnatal depression and enhance the neurodevelopment of the unborn child.
Name of contact:
Email of contact:
Maria Makrides
maria.makrides@health.sa.gov.au
NHMRC Research Achievements - SUMMARY
University of Melbourne
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
145627
Prof Christos Pantelis
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$355,000.00
Standard Project Grant
Title of research award: A study of the medial temporal lobe in high-risk and established schizophrenia using T2
relaxometry
Lay Description (from application):
Neurodevelopmental models of schizophrenia suggest that this disorder is associated with a structural brain
abnormality present from very early life. This model predicts that brain changes are present before the onset of
schizophrenia, and do not change. Our work supports the idea that damage is present from the outset of illness however, this damage was not evident in a high-risk group of individuals who later developed psychosis. When
these patients were rescanned after the onset of the illness, they exhibited reductions in the volumes of structures
that are regarded as critical to the symptoms of schizophrenia. The lack of structural changes in this group before
the onset of psychosis may have a number of possible explanations. However, it may be that a number of factors
produce the observed changes in the temporal lobe in schizophrenia. Thus, high-risk subjects may have a
vulnerability to hippocampal damage that becomes apparent during the transition to psychosis. In order to explore
this, our study will examine changes in the hippocampi in three groups of patients, and compare them with
matched normal control subjects. The patient groups are: (i) individuals at high-risk, (ii) first-episode psychosis
patients and (iii) patients with chronic schizophrenia. The study will rescan the high-risk group to examine
hippocampal changes once they have become psychotic. T2 relaxometry is a non-invasive way to examine
whether changes in the brain are present in patients with schizophrenia from the outset of illness. T2 will also let
us examine the high-risk individuals to see whether such changes are also apparent premorbidly. Using T2 we will
be able to examine the nature of these structural changes and assess what processes are in evidence. Our MRI
findings present a challenge to the neurodevelopmental hypothesis of schizophrenia. The use of T2 in this study
will allow a thorough examination of these findings and will have major implications for this hypothesis.
Research achievements (from final report):
Our study was designed to investigate patients with first episode psychosis, and also young people at very high
risk of developing psychosis. We were particularly interested in a brain region called the medial temporal lobe,
which is important for learning, memory and emotion. This region is known to be smaller in volume in people
with schizophrenia, but it is not clear whether smaller automatically means more damaged. We used a number of
new techniques to look at this region earlier in the illness. Our major finding was that there were no major changes
to the chemistry of the medial temporal lobe, either in early psychosis or before its onset. However, there were
subtle differences in energy metabolism and an antioxidant called glutathione in some patients, suggesting that
they might be undergoing an active process causing damage to the region. Further, we showed that verbal memory
is unimpaired prior to the onset of psychosis, and subsequently only affected in those with a diagnosis of
schizophrenia. This has implications for our understanding of psychotic disorders, in that there may be more
involvement of the medial temporal lobe in some diagnoses than in others.
Expected future outcomes:
Future outcomes include the follow-up of the patient group to establish whether there are active changes in brain
chemistry over the early part of the illness. We expect our data to guide research into the medial temporal lobe in
psychosis, specifically regarding diagnostic specificity. This should provide benefits in terms of understanding the
mechanisms that can lead to psychotic disorders.
Email of contact:
sjwood@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
145737
Prof Patrick D McGorry
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$345,548.00
Standard Project Grant
Title of research award: The role of stress, HPA-axis dysfunction and CNS structural and functional change in
the development of psychosis
Lay Description (from application):
This research will further understanding of the processes underlying the development of serious mental illnesses
such as schizophrenia and may lead to the development of strategies to prevent these devastating disorders.
Although there have been advances in the management of psychotic disorders in recent years, their underlying
causes remain largely unknown. We aim to investigate the potential roles of stress, HPA-axis function and
structural and functional brain changes. The neurodevelopmental model of psychosis suggests that small structural
CNS changes occur very early in life conferring a degree of vulnerability on the affected individual. We propose
that the psychological and neurobiological processes listed above interact with the pre-existing vulnerability,
resulting in the development of psychotic symptoms. This is in line with the stress-vulnerability model of
psychosis. We aim to investigate this model by monitoring the level of stress reported by young people at risk of
psychosis over 12 months. We will also obtain measures of their biological response to stress by assessing cortisol
levels over time and brain structure and functioning will be assessed. By monitoring these processes in the high
risk group, we will be able to identify any changes that occur if a psychotic illness develops. This research also
has practical applications in the identification of young people at high risk of developing a psychotic disorder,
Moreover it will inform the development of medical and psychological strategies aimed at preventing or delaying
the onset of schizoprenia and related illnesses in the high risk population.
Research achievements (from final report):
This project sought to investigate the potential roles of stress, HPA-axis function and structural and functional
brain changes in the development of psychosis in vulnerable young people. The neurodevelopmental model of
psychosis suggests that small structural CNS changes occur very early in life conferring a degree of vulnerability
on the affected individual. It was proposed that the psychological and neurobiological processed associated with
the experience of stress might interact with the pre-existing vulnerability, resulting in the development of
psychotic symptoms. This is in line with the stress-vulnerability model of psychosis. Preliminary analysis has
indicated that HPA-axis functioning in young people at heightened risk of psychosis is associated with the level of
psychological stress and the level of psychiatric symptomatology experienced. Hippocampal structure was not
associated with HPA-axis paramenters. Further analysis is required to determine the longitudinal relationships
between these variables- particularly in those young people who developed an acute psychosis.
Expected future outcomes:
This project has practical applications in the identification of young people at heightened risk of developing a
psychotic disorder. Moreover, it will inform the development of medical and psychiological strategies aimed at
preventing or delaying the onset of schizophrenia and related illnesses in the high risk population.
Name of contact:
Email of contact:
Lisa Phillips
lisa.phillips@mh.org.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
145760
Prof Henry J Jackson
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$355,000.00
Standard Project Grant
Title of research award: Standard Project Grant
Lay Description (from application):
The project aims to test the efficacy of two treatments to determine whether 'integrated' psychological treatment
leads to better outcomes for those individuals presenting for treatment for the first time. Neuroleptic medication is
the main treatment for the positive symptoms (i.e., delusions, hallucinations and thought disorder) which typify
the psychoses, including schizophrenia. Yet, there are reasons why other approaches should be investigated.
Firstly, not all patients respond to medications. Secondly, medication may not totally alleviate the positive
symptoms, and thirdly, other aspects of the condition are not helped to any extent by medication. These aspects
include negative symptoms (e.g., lack of motivation and asociality), depression, social anxiety and functioning in
the various life domains, e.g., school, work and socialization. In the last 15 years a viable psychological treatment
known as cognitive-behavioural therapy (CBT) has emerged. This appears to be effective in the treatment of
hallucinations and delusions and has an effect over and above that produced by medication. However, such
treatments have not yet been applied to treating those symptoms in first presentation psychotic patients when they
are in the acute stage of their illness. It is important to determine whether CBT produces positive effects in this
group and whether used in conjunction with medication it can produce greater and more rapid reductions in the
level and severity of positive symptoms. Whilst CBT is expected to produce positive changes in delusions and
hallucinations, the applicants believe this needs to be integrated with CBT interevention focussed on other aspects
of a patient's presentation, such as negative and depressive symptoms, and also on improving functioning in
various life domains.
Research achievements (from final report):
The study tested Cognitive Behaviour Therapy (known as ACE) in patients with first episode psychosis. The study
was conducted in one site. Patients were aged between 15 and 30 and were randomly assigned to one of two
groups; CBT or Befriending. All patients received treatment as usual, including low dose medication and case
management. All patients participated in the trial at four weeks following their registration with the service. For
both conditions treatment was conducted over a 10-14 week period, with a maximum of 20 sessions. 62 patients
participated in the trial and ACE outperformed Befriending on a range of symptom and functioning measures.
This is the first study of its kind in the world and is seen to be the best test of CBT in the acute phase of psychotic
illness.
Expected future outcomes:
It is still not known whether the results will hold up over the one-year follow-up period and we are still in the
process of assessing 5 remaining patients. The data collection will be complete by Christmas 2004.
Name of contact:
Email of contact:
Henry Jackson
henryjj@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
149230
Prof George C Patton
Epidemiology
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$450,939.00
Standard Project Grant
Title of research award: Psychosocial disorders of Youth: a population based prospective study into young
adulthood
Lay Description (from application):
Much earlier work in adults has pointed to the teens as a common point at which many of the important causes of
chronic disease and disability in adults begin. These include problems such as tobacco use, depression and anxiety
disorders, obesity, alcohol abuse and illicit drug use. However, only a prospective study is able to clarify to what
extent common health risk behaviours of teenagers pose a threat to later health and well-being and what
characteristics indicate those most likely to go on to problems such as nicotine dependence, recurrent depression
and illicit drug abuse. The proposal deals with the follow-up ten years on of a representative sample of 2000
Victorian teenagers. Seven earlier waves of data collections have ascertained levels and risk factors for common
behavioural and mental health problems in the teens and early twenties. These problems included depression and
anxiety, smoking, heavy alcohol consumption, illicit drug use, deliberate self-harm, obesity, eating disorder,
sexually risky behaviour, intravenous drug use, antisocial behaviours and accidental injury. This follow-up of
participants at the age of 24 to 25 years will ascertain persisting rates of these problems including levels of
substance dependence and mental disorder. Social outcomes such as educational achievement, employment,
relationships, parenthood and friendships will be ascertained. In addition mouth washes will be used to collect
DNA to allow investigation of genes that may make a contribution to more severe mental disorder and substance
dependency. This study will give a clear picture of the outcome and consquences of common adolescent health
problems. It will also clarify further psychosocial factors that contribute to their onset or outcome. Together with
an analysis of candidate genes the study should make a great contribution to the information necessary for
planning effective preventive intervention.
Research achievements (from final report):
The study has made an international impact with its publications in the areas of determinants of depressive
disorder and substance dependence syndromes as well as their effects on social development. Publications have
appeared in leading general medical (eg BMJ) as well as leading specialist journals. Some of the findings (eg the
health effects of cannabis use) have altered drug policy debates in the western world.
Expected future outcomes:
We plan a ninth wave of follow-up when the cohort participants are in their late twenties. This will allow us to
determine whether successful social adaptation in young adulthood has an effect on rates of mental and
behaivoural disorders. Current papers are dealing with the natural history of tobacco and alcohol use.
Name of contact:
Email of contact:
Professor George Patton
george.patton@rch.org.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
208937
A/Pr Sandra M Rees
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$210,000.00
Standard Project Grant
Title of research award: Investigating the validity of prenatal insults as risk factors for schizophrenia
Lay Description (from application):
Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The
cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An
adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In
guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus
disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and
neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with
schizophrenia. We will also assess whether behavioural responses of compromised animals are altered in tests that
parallel disturbances seen in patients with schizophrenia. Such abnormal brain development could create an
underlying vulnerability in the brain, predisposing individuals with risk factors such as genetic inheritance to
develop the symptoms of schizophrenia in later life perhaps only after the complete formation of nerve pathways
involved in higher brain functioning. If guinea pigs that have been subjected to low oxygen levels during
pregnancy show sustained changes in the structure and neurochemistry in regions of the brain that are altered in
patients with schizophrenia it would suggest that these long lasting disturbances could result from problems
during pregnancy. Thus, this would support the idea that abnormal brain development during pregnancy is one of
the underlying causes of schizophrenia.
Research achievements (from final report):
Schizophrenia is one of the most devasting of human mental disorders affecting about 1% of the population. The
cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An
adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In
guinea pigs we have investigated whether disruption to the normal supply of oxygen and nutrients to the fetus
disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and
neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with
schizophrenia. The advantage of our model over previously ued models is that it mimics a situation which could
occur in pregnant women. We found that at adolescence animals compromised during gestation have reduced
brain weight, enlarged lateral ventricles, reduced basal ganglia volumes, but no obvious signs of brain
degeneration. This outcome parallels some of the changes observed in patients with schizophrenia. We also found
impairment of the behavioural test, prepulse inhibition of the startle response, which is also observed in
schizophrenia. These results indicate that adverse prenatal conditions lead to long term alterations in brain
structure and function which resemble alterations seen in patients with schizophrenia and therefore supports the
early neurodevelopmental hypothesis of schizophrenia. The more we understand about the possible causes of this
debilitating disorder the better we can treat it and deal with it in the community.
Expected future outcomes:
This project was completed in the designated time frame and the expected future outcomes of this project will be
the preparation and acceptance of a number of manuscripts resulting from work completed during the tenure of the
grant, including an initial review for Clinical Experimental Pharmacology and Physiology.
Name of contact:
Email of contact:
A/Prof Sandra Rees
s.rees@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
209046
A/Pr Brian Dean
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$352,500.00
Standard Project Grant
Title of research award: Muscarinic receptors in schizophrenia
Lay Description (from application):
The research outlined in this proposal will examine the molecular make up of certain regions of the human brain
and determine if components within those regions are altered in tissue from subjects with schizophrenia.
Schizophrenia is a serious psychiatric illness that affects approximately 1% of the Australian population and the
research described in this proposal seeks to help understand the cause of the illness and/or to assist in the
development of new drugs with which to treat the illness. The goal of the research outlined in this proposal is to
determine if there are changes in specific molecules in the brain, termed muscarinic receptors. The muscarinic
receptors are one way that a chemical in the brain called acetylcholine can communicate with the nerve cells in the
brain. Acetylcholine is known to control important functions of the brain such as in memory, cognition and
learning, all of these functions are thought to be affected in schizophrenia. Importantly, the control of all these
functions involve muscarinic receptors and therefore, changes in those receptors could well produce some of the
symptoms of schizophrenia. We now wish to extend our early studies which suggest there may be changes in
muscarinic receptors in the brain of subjects with schizophrenia to determine which of the 5 muscarinic receptors
are affected in which region of the brain by the pathology of the illness. From our existing data, we would predict
that these studies will add weight to the argument that muscarinic receptors are altered in schizophrenia and
provide vital information as to how drugs that target these receptors may be used to treat the illness.
Research achievements (from final report):
Establishing that muscarinic receptors are affected by the pathology of schizophrenia and adding to a growing
body of data suggesting the use of muscarinic receptor agonists will be useful drugs to treat certain symptoms of
the disorder. Showing the changes in muscarinic receptors are affect in different regions of the brain and that this
may be why muscarinic receptors could be involved in causing the different symptoms experience by subjects
with schizophrenia. For the first time, showing that only one of the five muscarinic receptors (the M1 muscarinic
receptors) is affected in the frontal cortex of the brains of subjects with schizophrenia which suggests that changes
in that receptor may be particularly involved in causing the cognitive deficits experienced by people with
schizoprhenia. Such deficits ( which mean an individual has problems with day to day living, have been suggested
as the greatest block to an individual with schizophrenia returning to a productive working life. The cognitive
deficits are problematic in that they do not respond well to treatment with available antipsychotic drugs.
Expected future outcomes:
We now have NH&MRC funding to fully examine the role of decreases in M1 receptors in the cognitive deficits
in schizophrenia. These studies will focus on how the gene for the receptor regulates levels of the receptor in the
frontal cortex obtained postmortem from schizophrenic subjects and how mutations in the gene may be associated
with cognitive deficits in living subjects with schizophrenia.
Name of contact:
Email of contact:
Brian Dean
bdean_mhri@iprimus.com.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
209062
Prof Patrick D McGorry
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2001
2004
$322,500.00
Standard Project Grant
Title of research award: Bioactive lipids in early psychosis
Lay Description (from application):
This study will investigate the role of fatty acids (lipids) in schizophrenia. Studies in blood cells and in the brains
of patients with schizophrenia have shown that these lipids and related products are altered in schizophrenia. We
are now able to measure separate lipid metabolites in the living human brain using a technique called magnetic
resonance spectroscopy. Until recently it was only possible to assess lipid metabolites as a group, limiting
interpretation. Thanks to a newly available imaging system at the Brain Imaging Research Institute and a new
analysis technique, we will be able to measure single lipid metabolites in the living human brain. Simultaneously
we will also measure lipids and related enzymes in red blood cells that are responsible for the regulation of these
lipids. Preliminary data has shown that there is a strong correlation between these two measures. Furthermore we
will investigate the genes that are responsible for the production of these enzymes. By repeating the same tests
after 12 weeks we hope to understand how the newer antipsychotic drugs act. Two easy clinical tests (a skin and
breath test) will help us to implement the findings in daily clinical practice (diagnostic markers for patients at risk)
. With such a multi-level approach we hope to contribute to a new understanding of the origins of schizophrenia
going beyond the traditional concepts. The findings might also have direct implications for treatment. Preliminary
results are very promising but also contradictory. Therefore it is even more important to carefully investigate the
role of these lipids in schizophrenia.
Research achievements (from final report):
Were able to assess bioactive lipid metabolism in living human brain, and blood and relate it with behaviour,
cognition and investigate influence of lipid candidate gene variations on lipid metablolism.
Expected future outcomes:
we expect to understand the underlying neurobiology of onset of pyychotic disorders
Name of contact:
Email of contact:
Gregor Berger
gregor@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
148947
Prof Anthony F Jorm
Mental Health
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2001
2005
$525,000.00
NHMRC Research Fellowship
Title of research award: SPRF
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The research has been aimed at two issues: (1) improving the public's understanding of mental disorders and (b)
finding out risk factors for mental disorders at various stages of life. Some achievements in each of these areas
are: (1) National surveys of public understanding in Australia have shown major improvments over recent years,
in terms of ability to recognize mental disorders, knowledge of what are appropriate treatments, and reduction in
negative attitudes. "Beyondblue: the national depression initiative" has been shown to be a factor in this
improvement. A number of specific interventions have been developed to improve public understanding and
found to be effective, including consumer guides, web sites and Mental Health First Aid training. (2) Depression
and anxiety disorders become less common as people age, partly because older people have fewer risk factors, but
also because the ageing brain is less prone to emotional extremes. However, there are some risk factors that
become more common with age, such as subtle damage to the white matter of the brain. Fortunately, this damage
is preventable through control of high blood pressure and perhaps through dietary changes which reduce a
substance called "homocysteine" in the blood.
Expected future outcomes:
As a result of the research, mental health first aid training has spread across Australia and is rapidly spreading in
other countries.
Name of contact:
Email of contact:
Anthony Jorm
ajorm@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
216742
Dr Lena A Sanci
Primary Health Care
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2002
2005
$0.00
Public Health (Australia)
Title of research award: Public Health Postdoctoral Training Fellowship
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
This postdoctoral training fellowship enabled me to further develop a) my skills as a researcher by using
methodologies not covered in PhD studies and b) my research expertise in the content area of young people's
health in primary care.This has culminated in me establishing and leading a Young People's research theme area in
the Primary Care Research Unit, Department of General Practice, University of Melbourne. The major aim of the
projects undertaken during the postdoctoral training fellowship was to examine the way primary care services
could re-orientate their focus toward health promotion, prevention and early intervention for young people's health
risk behaviour and mental health issues. Two scoping projects provided results on the enablers and inhibitors of
general practice providing this care to young people and the type of intervention that may be necessary. These
results provided the foundation for two successful applications for competitive grants (Australian Health
Minister's Advisory Council and Australian Primary Care Research Institute) to run a randomised trial of a general
practice intervention that enables health risk screening and counselling for young people, including higher risk
young people, presenting to general practice. The role of the practice nurse is also to be explored in this work.
This trial is currently underway and will be completed in 2009. It involves significant national (Vic, NSW) and
international collaborators (UK, US, Can) in research, practice and policy areas. It will provide the first evidence
for effectiveness of preventive health care for young people in Australia and will inform policy and practice.
Expected future outcomes:
Establish an evidence base for primary care interventions to address young people's access to health care, their
health risk behaviours and mental health issues
Name of contact:
Email of contact:
Lena Sanci
l.sanci@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
251730
Prof David L Copolov
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$325,000.00
Standard Project Grant
Title of research award: Efficacy of treatment for resistant command hallucinations
Lay Description (from application):
Auditory hallucinations (AHs), often described as "voices", are a common symptom of schizophrenia and
psychoses. Command hallucinations (CHs) are a type of AH in which the voice heard by the patient commands
him or her to perform a particular action. The nature of the directive may vary from inconsequential actions to
commands to harm the patient or others. There is widespread public concern about the danger individuals with
schizophrenia or related disorders pose to themselves and to the community. There is firm evidence pointing to the
important role that CHs play in propelling psychotic individuals into serious and damaging actions. We have
found, however, that most individuals who comply with dangerous CHs do so, not because they are angry, violent,
antisocial or wish to cause harm, but because they feel powerless to resist. Though CHs are one of the most
disturbing symptoms of psychosis, standard treatment has proved to be of limited benefit. This study will evaluate
the effectiveness of Treatment of Resistant Command Hallucinations (TORCH), an innovative treatment for CHs.
TORCH is an extension of an existing treatment for psychosis that we previously developed. TORCH aims to
reduce the distress, worry and harmful or self-defeating behaviour associated with CHs by arming the patient with
effective strategies that will enhance resistance and reduce compliance. The project has clear implications for
improved clinical and therapeutic management of CHs with major public health, clinical and forensic
repercussions. The consequences of being formally assessed as being at risk of acting violently result in the
potential for substantial restrictions on the freedom of the individual. The availability of TORCH may prompt a
less restrictive management of individuals at risk of dangerous behaviour and promote a more optimistic attitude
amongst clinicians. Relatives and carers also stand to benefit through reduction in perplexing and fear-inducing
behaviours.
Research achievements (from final report):
Command hallucinations (CHs) are a form of auditory hallucination experienced by some individuals with
schizophrenia and related psychoses that instruct the person to perform an action(s). CHs sometimes incite
harmful actions and are associated with greater levels of disability and distress compared to non-command
auditory hallucinations. This project is examining whether a psychological intervention, TORCH (Treatment of
Resistant Command Hallucinations), reduces compliance with problematic CHs and improves well-being.
TORCH is a functional form of Cognitive Behaviour Therapy that has been adapted to CHs. It focuses on
reducing the power of CHs to cause action and developing alternative behaviours that are independent of CHs.
The evaluation of TORCH is being undertaken by comparing it with a control condition, 'Befriending'. In
Befriending, participants receive an equal amount of therapist contact, in the form of positive and enjoyable social
conversation and activity, but not the specific components of TORCH. The project has progressed steadily with
low attrition and high levels of participant satisfaction with both treatments. However, due to delays in
recruitment, the project has been extended one year and will conclude December 2006. Although the main
outcome results are not yet available, client feedback data indicate that participants responded positively to both
treatments with 85% stating that their therapy sessions made them feel "better" or "much better". TORCH
participants gave significantly higher ratings for problem improvement compared to Befriending participants.
Ninety percent of TORCH participants said their sessions made the problem of CHs "better" or "much better"
compared to 59% of Befriending participants.
Expected future outcomes:
Command hallucinations are a common symptom of schizophrenia and standard treatment has proved to be of
limited benefit. The findings from this project will have clear implications in relation to the clinical and
therapeutic management of this disturbing symptom.
Name of contact:
Email of contact:
Dr Fran Shawyer
fshawyer@mhri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
194240
Dr Andrew J Lawrence
Basic Pharmacology
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2002
2006
$475,000.00
NHMRC Research Fellowship
Title of research award: SRF
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Over the 5 year period of this fellowship, I published 48 journal articles comprised of 42 original articles and 6
reviews. All of these publications were subjected to peer review. During the preceding 5 years to date, my
research articles have been cited over 300 times. The main achievements of this research have been the
characterisation of the role of brain peptide systems in the use and abuse of alcohol; how the brain integrates
psychological stressors resulting in a patterned response; the impact of chronic administration of therapeutic drugs
(such as antidepressants) or novel candidates upon brain chemistry and structural plasticity; glutamate and
glutamate receptors as a target for drugs of abuse and alcohol. Moreover, my research has highlighted a number of
potential therapeutic targets for drug and alcohol abuse disorders. One example is the mGlu5 receptor where our
findings have been widely acknowledged and have resulted in invitations to speak at international conferences.
During this period I was awarded a Fellowship of the British Pharmacological Society, 3 Young Investigator
Awards and was invited to join the editorial boards of a number of journals (British Journal of Pharmacology,
American Journal of Physiology, Addiction Biology).
Expected future outcomes:
I am still actively pursuing a number of these research leads, and integrating them with new directions that have
been indicated by our findings. In addition, my laboratory has developed the ability to generate transgenic mice
with conditional (restricted) deletion of genes with anatomic and/or developmental regulation to tackle these
questions in a complementary manner.
Name of contact:
Email of contact:
Andrew Lawrence
Andrew.Lawrence@florey.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
359286
Start Year:
2005
CIA Name: Dr Mark A Bellgrove
End Year:
2006
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$171,000.00
Admin Inst: University of Melbourne
Grant Type: Howard Florey Centenary
Fellowship
Title of research award: The genetic architecture of attentional dysfunction in Attention Deficit Hyperactivity
Disorder
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
This project aimed to examine the relationship between genes that code for neurotransmitters in the brain and
objective markers of cognitive dysfunction in attention deficit hyperactivity disorder (ADHD). ADHD is a
heritable disorder of childhood with negative adult outcomes. A number of genes have been identified, such as the
dopamine transporter gene, that appear to confer risk to the disorder. This project asked whether laboratory
measures of attention and working memory were influenced by DNA variation in these same genes in children
with ADHD. Through collaborations with local and international teams we have identified that DNA variation in
the dopamine transporter gene influences the ability of both children with ADHD and normally developing
children to control their attention, particularly within the spatial domain. Further we have shown that measures of
spatial attention are able to predict symptom improvements achieved with stimulant medications, such as
methylphenidate. This project has also developed a number of novel probes of cognitive (attention and working
memory) dysfunction for children with ADHD which we continue to develop and administer to children with
ADHD with the aim of further understanding how DNA variation might give rise to cognitive impairments in
ADHD.
Expected future outcomes:
The recruitment of children with ADHD initiated under this fellowship is ongoing and we are expanding the
project to include sites in Melbourne, Perth and Brisbane. We hope to identify whether particular patterns of
cognitive deficit in ADHD are heritable and whether subgrouping children according to whether they have
impaired or intact cognitive function may help to clarify the genetics of ADHD.
Name of contact:
Email of contact:
Mark Bellgrove
m.bellgrove@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
299869
Prof Jane M Gunn
Primary Health Care
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$450,000.00
Standard Project Grant
Title of research award: Diagnosis, Management and Outcomes of Depression in Primary Care: a longitudinal
study - Diamond
Lay Description (from application):
Depression is the single largest cause of disability for people in Australia. It is mainly managed in general
practice, yet many people experiencing depression go unrecognised by their family doctor or general practitioner
(GP). Some people, even when given treatment, remain depressed. Guides on how to manage depression have
been mainly based upon people attending psychiatrists and hospitals. In addition, there have been a number of
large studies overseas testing new ways of helping people with depression. Unfortunately, they do not seem any
better than usual care by a GP. The proposed DIAMOND study will follow, over time, 900 people who receive
care in general practice to investigate the factors, from the patients' and doctors' point of view, that are likely to
aid recovery from depression, and prevent further episodes. We will investigate in detail the way in which a
patient is cared for in the primary health care system. We will be able to describe the care patients receive from
both doctors and other professionals, including alternative practitioners. This information will be used to develop
a new way to improve the care that GPs provide to people experiencing depression. DIAMOND will give us
important information about the impact of new Government policies on care in general practice. This will help to
inform health workers, consumers and policy makers about what factors are key for treatment and recovery from
depression.
Research achievements (from final report):
A cohort of 790 participants with depression symptoms were recruited to the study with data collected at
screening, baseline, 3 months, 6 months, 9 months and 12 months. Depression is the fourth most common problem
managed in general practice however there is very little longitudinal data available on primary care users with
symptoms of depression. Through the use of quantitiative and qualitative methods the diamond study investigates
what health services are being accessed by the cohort and whether these services are meeting the needs of the
participants, co-morbidities, medication use, precipitating and perceived factors for depression, symptoms of
depression disorders and quality of life measures. The longitudinal nature of the study enables outcomes in the
primary care of depression to be assessed and mapped and an exploration into the factors that effect outcomes of
care (GP characteristics, patient characteristics and system factors) along with enablers and barriers to the
management of depression in primary care and the costs associated. Such information can then be utilised to
inform health policy and best models of care for depression in primary care.
Expected future outcomes:
The project has been awarded extended funding for another two years in which exploration of patient
characteristics, system factors, treatment factors and health service use related to depression outcomes will be
explored in order to develop models of care that will work in the general practice and primary care setting.
Name of contact:
Email of contact:
Professor Jane Gunn
j.gunn@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300081
Start Year:
Dr Michelle A Kermode
End Year:
Public Health and Health Services not elsewhere classified
University of Melbourne
Grant Type:
Fellowship
2004
2007
Total funding: $0.00
Public Health (Australia)
Title of research award: Public Health Post-doc Fellowship
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
During the four years of her NHMRC Public Health Post-doctoral Fellowship, Michelle Kermode successfully
undertook eight studies in different aspects of public health in a low-income country setting (India) including:
medical injection safety, HIV, injecting drug use, sex work and mental health. She has attracted funding for this
work from the University of Melbourne, the UK government's Department for International Development (DFID),
the Australia-India Council, and the Gates Foundation. Through this program of work Michelle has made a direct
contribution to HIV and mental health programs in India. She has also augmented Australia's contribution to
international public health by building sustainable partnerships and local research capacity in the region. For
example, her work on mental health promotion as a strategy for HIV prevention had a profoundly positive impact
of the well-being of vulnerable women in north-east India. This approach can be applied in a range of settings and
has the potential to contribute to a reduction in HIV risk behaviours. The implementation of this project and the
evaluation of its impact also built the research capacity of local staff in a very under-developed part of the world.
Expected future outcomes:
The foundations laid down by the program of international public health research undertaken by Michelle
Kermode during the course of her NHMRC Fellowship is currently being strengthened and expanded through the
award of new work such as a study on female drug use in north-east India, beginning in 2008.
Name of contact:
Email of contact:
Michelle Kermode
mkermode@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
350344
A/Pr Brian Dean
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$660,585.16
Standard Project Grant
Title of research award: Muscarinic M1 receptor, cognition and schizophrenia
Lay Description (from application):
Schizophrenia is a serious psychiatric illness that affects approximately 1% of Australia's population. Whilst the
prominent symptom of schizophrenia is psychosis, the majority of subjects with schizophrenia also show deficits
in cognition. Unlike psychotic symptoms, deficits in cognition do not respond well to current antipsychotic drug
treatment. We have been investigating the possible role for changes in a family of receptors, called muscarinic
receptors, in the pathology of schizophrenia for almost a decade. Our research has shown that two members of the
muscarinic receptor family, the M1 and M4 receptors, may be differentially decreased in different brain regions of
subjects with schizophrenia. Recently, we have shown that in the dorsolateral prefrontal cortex, the muscarinic
receptor that is decreased in schizophrenia is the M1 receptor. Since we made this discovery another group has
shown that a mutation in the M1 receptor may be a cause of cognitive deficits in schizophrenia. We are now
proposing a study using parallel streams of research on postmortem brain tissue and in living subjects with
schizophrenia to determine the likelihood that decreases in M1 receptors in the cortex may be the cause of
cognitive deficits in schizophrenia. This will involve confirming that mutations in the M1 receptor, measured
using DNA from white blood cells, are associated with cognitive deficits in schizophrenia. At the same time we
will determine if the same mutation is associated with low levels of M1 receptors in cortex obtained postmortem
from subjects with schizophrenia. If both these are true this will give us a strong platform to suggest that low
levels of cortical M1 receptors are associated with cognitive deficits in schizophrenia.
Research achievements (from final report):
Two major milestones were reached on completion of this project. The first was the identification of a subpopulations, definable by stringent staistical analyses, of subjects with schiziophrenia (~ 25%) who had lost on
average 75% of the muscarinic receptors in their dorsolateral prefrontal cortex. Given that muscarinic receptors
and the dorsolateral prefrontal coretx are critical in maintaing cognition in humans we hypotesise that the losss of
muscrinic receptors in the cortex of subjects with schizophrenia will be involved in the cognitive deficits
associated with the disorder. An extension of our hypothesis is that the subjects with schizophrenia who have lost
most of their cortical receptors, which we have termed Muscarinic Receptor Deficit Schizophrenia, will be
particularly at risk from cognitive deficits. The second major finding is that subjects with schizophrenia who have
a particular SNP in the muscarinic M1 receptor have high levels of cognitive deficits. We have shown this high
level of cognitive dysfunction is not associated with altered levels of gene expression and therefore it remains to
discover the mechanism by which such a small change in the human genome can be associatedw with changed
cognitive functioning in schizophrenia.
Expected future outcomes:
A number of pharmaceutical companies are developing drugs that act at muscarinic receptors. It is pedicted that
these drugs will have both antipsyhcotic and cognitive enhanceing effects. Our findings suggest that either a
neuroimaging test or gentic tests of the muscrinic receptor may provide biomarkers to direct the use of these drugs
when treating schizophrenia.
Name of contact:
Email of contact:
Brian Dean
anddali@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300054
A/Pr Jane E Pirkis
Mental Health
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2004
2008
$417,500.00
Population Health CDA
Title of research award: Preventing suicidal behaviours: Ecological studies of systemic protective factors
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Most international research efforts in suicide prevention have focused on exploring the rates of and risk factors for
suicidal behaviour. My program of work considered some of the factors that might be protective against suicide at
a range of levels (individual, ecological, intervention/service-based, systemic). My work has influenced policy and
practice in a number of ways, including helping to shape national and international guidelines on media reporting
of suicide, and influencing the nature of several national mental health and suicide prevention initiatives.
Expected future outcomes:
I would anticipate that my work will continue to have an impact on policy and practice in a similar manner.
Name of contact:
Email of contact:
Jane Pirkis
j.pirkis@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
350241
Start Year:
Prof Patrick D McGorry
End Year:
Medical and Health Sciences not elsewhere classified
University of Melbourne
Grant Type:
2005
2008
Total funding: $7,397,980.00
New Program Grant
Title of research award: Emerging Severe Mental Illness in Young People: Clinical Staging, Neurobiology,
Prediction & Intervention from Vulnerability to Recovery
Lay Description (from application):
Mental disorders, such as psychotic and severe mood disorders, are the largest cause of disability in Australia.
However, there is still little known about illness onset, relapse and progression. We have developed a clinical
staging model with transition points from symptomfree to subthreshold status, to threshold disorder to chronic
disability. We will investigate neurobiological and psychosocial factors which increase the risk of progression
through these stages and use this model as a basis for examining the effectiveness of interventions, for example to
prevent, delay or ameliorate onset and relapse, and promote vocational recovery. Thus major clinical and public
health benefits and an understanding of factors that contribute to the onset and progression of illness will result.
Research achievements (from final report):
This program grant investigated various aspects of youth mental health, our achievements to date have included
the following: Our longtitudinal studies have clearly demonstrated that the family environment, specifically
patterns of interactions between parents and their early adolescent children, is a strong risk factor for the
emergence of mental health problems, and also interacts with biological risk factors to further increase risk for
these types of problems. Our studies have been able to give a fine-grained understanding of the specific patterns of
interactions that are most problematic, which will lead to the design and implementation of family based
preventative strategies that are targeted at those most at risk. We carried out the first ever randomised controlled
trial of a vocational intervention in young people with a first episode of psychosis and demonstrated a highly
effective way to help this marginalised disability group to find employment in the open labour market. This study
provides hope and a better future to young people with first episode of psychosis. Our research into stress/trauma
and psychosis has provided a greater understanding of the impact of stress and prior exposure to trauma on young
people recovering from a first episode of psychosis, which could in the future lead to advancement in novel
therapeutic intervention treatments that aim to mitigate the adverse effects of stress and improve outcome. In
addition we have shown that the progressive change in brain structure across the early phase of psychotic
disorders could potentially be prevented by treatment with neuroprotective agents such as lithium or omega-3 fatty
acids. Our newly-established clinics in Sydney have shown that young people with early depressive symptoms
who are also at risk of major mental illness have changes in neuropsychological function before they develop
severe disorders. The extent of these changes is similar to those who go onto develop psychotic disorders.
Expected future outcomes:
We plan to pursue a range of research studies that involve understanding the opportunities and vulnerabilities
associated with early adolescent development, functional and social rehabilitation in people with emerging
psychotic illness. Our studies will also investigate new interventions that aim to more effectively engage and treat
young people with an emerging mental illness.
Name of contact:
Email of contact:
Prof Patrick Mcgorry
pmcgorry@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
359284
Dr Meghan L O'Donnell
Health, Clinical and Counselling Psychology
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2005
2008
$264,000.00
Australian Clinical Research
Title of research award: Posttraumatic mental health following traumatic injury: Enhancing resilience and
recovery
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
This research has made a substantial contribution to understanding the mental health problems that people may
develop following serious injury. In one of the largest studies of its kind, we identified that 23% of injury patients
went on to develop psychiatric disorders that they had never experienced before including posttraumatic stress
disorder, depression, generalised anxiety disorder, panic disorder and social phobia. We developed a world first
screening instrument that identifies shortly after injury patients at high risk for developing later PTSD or
depression. We develop a model of best practice for delivering early psychological intervention to those patients
who are at risk for developing anxiety and depressive disorders folloiwng injury. This model recognises that the
majority of those who develop mental health disorders will do so after discharge from hospital, and that the
majority will not seek treatment for their disorders. The model involves screening patients in hospital to identify
those at high risk for developing mental health disorders. Those at high risk are followed up at one month post
injury and reassessed. Those with high anxiety and/or depression at this point are referred to a clinical
psychologist who conducts a more thorougher assessment. The psychologist then refers patients for early
psychological intervnetion. We conducted a pilot study to test this model in an effectiveness study. The pilot study
revealed a number of barriers that prevent patients accessing treatment for their psychological problems. We have
designed future studies that aim to address these barriers to mental health care.
Expected future outcomes:
A number of Australian and international trauma services are currently using our screening instrument and their
practice has been informed by our model of service delivery. We aim to conduct a number of studies that further
increase our understanding of the factors that contribute to poor recovery following injury, and improve
intervention strategies.
Name of contact:
Email of contact:
Meaghan O'Donnell
mod@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
400088
A/Pr Terence J O'Brien
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$372,625.00
Standard Project Grant
Title of research award: STRESS, HYPERCORTISOLAEMIA AND LIMBIC EPILEPTOGENESIS.
Lay Description (from application):
This project has the potential to provide novel insights about the causal connections between stress, psychiatric
illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of
medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and/or
depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic
epileptic condition. However, recent evidence suggests that there is a bi-directional relationship, with the
psychiatric conditions and stress also acting to aggravate the seizures and even predispose to the development of
the epilepsy itself. Apart from gaining insights into causes of TLE, anxiety and depression, this framework has
potential public health relevance suggesting approaches to the eventual primary and secondary prevention of both
MTLE and its associated psychiatric co-morbidities, a neglected area at present. The use of an animal model
allows investigation of aetiological processes that extend over the lifetime, which is exceptionally difficult to
achieve in humans. Retrospective studies, such as case-control studies, although an indispensable research
methods, are subject to bias and imprecision when it comes to measuring remote past exposures to stress, abuse,
and deprivation. If the results of these experiments are consistent with our hypotheses, a very strong case would
exist for exploring this relationship in human studies. The data would also provide a strong rationale for more
aggressive detection and treatment of these psychiatric co-morbidities in TLE patients, in order to potentially
modify the progression of the disorder as well as improve the quality of life of sufferers. The results of
intervention studies in animal models may suggest specific mode of treatment to achieve this.
Research achievements (from final report):
Temporal lobe epilepsy is the most prevelant form of epilepsy affecting adults. More than 30% of patients with
TLE have a significant co-morbid mood disorder. This project investigated the link between stress, mood
disorders and epileptogenesis using a rat models. The project was highly successful and productive: in terms of
publications, student, and collaborations. It has formed the ground work for our new project NHMRC grant
commencing in 2009, as well as the New Investigator NHMRC grant of the Post-Doctoral Fellow working on this
project. There were 2 major parts: The first part of the study demonstrated that concurrent stress accelatated the
progression of epilepsy in a rat model of temporal lobe epilepsy. The second part demonstrated that early postnatal
stress, in the form of maternal separation, creates vulnerability to limbic epileptogenesis in adult life. The study
also made important scientific discoveries about the mechanisms underlying the effects of stress on
epileptogenesis.
Expected future outcomes:
The study has provided experimental proof-of-concept that co-morbid stress aggravates limbic epileptogenesis.
The results lay the groundwork for future clinical studies that will investigate whether pharmacological or
psychological treatment of co-morbid mood disorders has benificial disease modifying effects on temporal lobe
epilepsy.
Name of contact:
Email of contact:
Terence O'brien
obrientj@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
400154
Dr Anthony J Hannan
Central Nervous System
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$515,000.00
Standard Project Grant
Title of research award: Gene-environment interactions and synaptic plasticity in the developing and
dysfunctional cerebral cortex
Lay Description (from application):
The cerebral cortex contains many billions of neurons, which are interconnected by trillions of synapses, to form
networks underlying our most complex brain functions. It is only after birth, with environmental stimulation, that
diverse brain functions begin to emerge. We are interested in the mechanisms whereby the genetic programme
regulating maturation of the cerebral cortex is sculpted by interaction with the environment, as well as ongoing
gene-environment interactions and mechanisms of plasticity in postnatal brain. Many brain disorders, including
schizophrenia, autism, epilepsy, Alzheimer's and Huntington's disease, involve abnormal development or function
of the cerebral cortex. Our group has recently demonstrated that onset and progression of Huntington's disease,
previously considered the epitome of genetic determinism, can be modulated by environmental factors, suggesting
that all brain disorders must involve gene-environment interactions. In this project we are focusing on a specific
molecular pathway which processes information from the environment and induces experience-dependent changes
in the structure and function of neurons in cerebral cortex. We know that the molecular pathway we are examining
has been linked to schizophrenia, a disorder of brain development, and we are attempting to understand how
disruption of these molecular pathways can lead to the abnormal brain development and plasticity seen in this
disease. We hope to discover neurobiological mechanisms which provide integrative understanding at the level of
molecules, networks of neurons, and behaviour, in mouse models of brain disorders with disruption of specific
genes, receiving different types of environmental stimulation. Analysing normal mice in this project will also
provide new information on mechanisms of plasticity in the healthy cerebral cortex, that may underlie higher brain
functions such as learning, which occurs throughout postnatal life, and memory.
Research achievements (from final report):
We have characterised new mouse models of schizophrenia, and found evidence for both genetic and
environmental contributions to disrupted brain development and plasticity. We studied mice in which a single
gene (out of over 20,000 in the mouse genome, which is similar to humans), and discovered that they exhibited
many striking behavioural abnormalities of relevance to schizophrenia. Some behavioural changes were shown to
be corrected by the antipsychotic drug, clozapine, suggesting that these models have direct relevance to clinical
studies. Furthermore, environmental enrichment of the mice, providing enhanced levels of mental and physical
activity, was found to prevent or correct many of the behavioural problems. This suggests that enhancement of
mental and physical activity in human populations could protective effects in those genetically at high risk of
brain disorders such as schizophrenia. While such a hypothesis needs to be tested in clinical trials, it provides a
framework for exploring the roles of genes and environment in schizophrenia and related disorders.
Expected future outcomes:
If we can provide further insights into these mouse models of schizophrenia, we may be able to guide future
development of therapeutic approaches, as well as biomarkers, for schizophrenia and related brain disorders.
Name of contact:
Email of contact:
A/Prof. Anthony Hannan
anthony.hannan@florey.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
454381
Prof Anthony F Jorm
Mental Health
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2007
2008
$157,500.00
Standard Project Grant
Title of research award: Self-help for depressive symptoms: finding messages suitable for population-wide
promotion
Lay Description (from application):
Members of the community often use self-help methods to reduce symptoms of depression. In some cases, these
may be effective, but in others they may do more harm than good (e.g. self-medication with nicotine or alcohol).
The project aims to find out which self-help methods are most likely to be helpful and are easy for the community
to use. These methods can then be promoted in educational campaigns to improve how people cope with
symptoms of depression. If people can take action to reduce milder levels of depression, this may prevent them
from progressing to develop a clinical disorder that needs professional treatment.
Research achievements (from final report):
Many people experience mild depressive symptoms that do not require clinical treatment. They generally deal
with these symptoms by using self-help methods. While some of these self-help strategies may be helpful, others
may not work or even make depression worse (e.g. use of substances). This project sought to determine key
messages about effective self-help for depressive symptoms that can be promoted to the general public. The
project involved 2 components (1) a systematic review of the evidence on self-help interventions for depression
and (2) a study of the consensus of depression experts and consumers affected by depression about which selfhelp methods are likely to be effective. The project identified 15 self-help strategies that are likely to be effective
and that are feasible for people with depressive symptoms to implement.
Expected future outcomes:
Future research will determine whether promoting these self-help messages to people with depressive symptoms is
effective in reducing symptoms and preventing the development of depressive disorders.
Name of contact:
Email of contact:
Anthony Jorm
ajorm@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
508919
Prof Anthony Jorm
Mental Health
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2008
2008
$158,500.00
Standard Project Grant
Title of research award: Mental health literacy and action to deal with mental health problems: a longitudinal
study of young Australians
Lay Description (from application):
Many young people with mental health problems do not get adequate professional help because they lack relevant
knowledge. This study will find out what type of knowledge is important for improving appropriate help-seeking
by young Australians. Young people who were surveyed two years earlier to assess their mental health knowledge
will be followed up to see whether they developed a mental health problem and what action they took to deal with
it.
Research achievements (from final report):
In 2006. a national survey was carried out with 3,746 young Australians aged 12-25 years to asess their
knowledge and attitudes to mental health problems, including depression, psychosis, anxiety disorder and alcohol
misuse. This survey found some major gaps between the beliefs of young people and those of mental health
professionals about what are the most appropriate interventions for mental health problems. In 2008, 2,005 of
these young people were re-interviewed to examine actions they took if they themselves developed a mental
health problem or one of their friends did. These data will be analyzed to find out what knowledge and beliefs
predict whether young people take constructive action when they or a friend develops a mental health problem.
Expected future outcomes:
The data will allow the development of a "core curriculum" of what is important for young people to know so that
they can take earlier and more appropriate action when mental disorders are first developing.
Name of contact:
Email of contact:
Anthony Jorm
ajorm@unimelb.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
509109
Prof Michael Berk
Psychiatry
University of Melbourne
Start Year:
End Year:
Total funding:
Grant Type:
2008
2009
$80,250.00
Standard Project Grant
Title of research award: The effect of high-dose vitamin D supplementation on mental health in a randomised
controlled trial of 1,500 older women.
Lay Description (from application):
Vitamin D is commonly deficient in Western populations, more so in the winter months and in the elderly. A link
between depression and vitamin D insufficiency may exist. This study aims to see if vitamin-D supplementation is
a practical health intervention for depressive symptoms and may define a public health strategy. In this study
participants receive a dose of vitamin D3 or placebo annually for three years. Self-rated psychiatric assessments
are administered.
Research achievements (from final report):
Recent evidence suggests that people with a higher level of vitamin D in their blood are less likely to suffer
depression or significant mood swings. This theory was tested in a randomised controlled trial in over 2,000 older
women where half the participants received vitamin D and half received placebo or 'dummy' tablets. The study
represents the first trial to test mood regulation using a large oral dose of vitamin D (500,000IU) given once a year
for 3 to 5 years. Approximately 1,300 participants completed questions about mood and mental well being. Blood
tests were done in 100 participants. Results from the blood tests suggest that those given the annual high dose
vitamin D tablets maintained a higher serum level of vitamin D for the entire year. Despite this, results from the
questionnaires do not show that those taking vitamin D felt better or had fewer depressive symptoms compared
with those on placebo.
Expected future outcomes:
The results raise questions about whether vitamin D supplementation would be an effective therapy to prevent
depressive moods. The results do not support a strong effect of higher serum vitamin D status on mood regulation
although future studies are needed to confirm this negative result.
Name of contact:
Email of contact:
Prof Michael Berk
mikebe@barwonhealth.org.au
NHMRC Research Achievements - SUMMARY
University of New England
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
209200
Dr Margaret L Brechman-Toussaint
Mental Health
University of New England
Start Year:
End Year:
Total funding:
Grant Type:
2002
2005
$60,000.00
New Investigator
Title of research award: Prevention of childhood anxiety: A parent-focused approach targeting the school
transition
Lay Description (from application):
The prevention of mental health problems in young people warrants research. Anxiety is a common problem
amongst children, resulting in academic and relationship difficulties across the lifespan. The project investigates
the effectiveness of an anxiety prevention strategy designed to optimise school adjustment in anxious and
withdrawn preschool aged children making the transition to formal schooling. The intervention is parent-focused.
Parents will be taught anxiety management strategies. They will also be taught to decrease the use of
overprotective or threat communicative responses, to model and reinforce non-anxious behaviour, and to coach
children in active problem solving. The prevention of childhood anxiety will have important cost savings in the
long term, relating to reduction in the costs associated with school adjustment difficulties and mental health
treatments for children, as well as reductions in distress amongst individuals and their families. If the present
program proves successful with children at risk of anxiety, it may have the potential to be offered within the
education system as a universal transitional program.
Research achievements (from final report):
This project investigated the effectiveness of an anxiety prevention strategy designed to optimise school
adjustment in anxious and withdrawn 4-7 year old children. One hundered and sixty families completed initial
screening for the research. Sixty-six families were found to be eligible based on significantly elevated child
anxiety. These families were randomised assigned to either an 8 week intervention program or an 8 week waiting
list control group. The intervention taught parents how to effectively deal with their children's anxious behaviour,
by decreasing use of overprotective and threat communicative responses and by modeling, reinforcing and
coaching non-anxious behaviour. Parent and teacher report of child anxiety before and after the 8 week period
were compared across groups. The results showed that according to teacher report, following the intervention,
children whose parents had participated in the program, were demonstrating less anxious behaviour at school than
children whose parents had been in the waitlist condition. Interestingly, there was no identifiable difference
between active treatment and waitlist child anxiety when parents reported on their child's behaviour. This
suggested that while children whose parents had been through the intervention were behaving less anxiously at
school, parents were recognising little difference on the home front. The findings from this research are limited
somewhat by small sample size and the lack of follow up data to see if positive outcomes were maintained.
Results need to be replicated with a larger sample and outcomes monitored long-term. If a replication study found
that the program successfully reduced child anxiety in the early school years and that this reduction was
maintained as children developed, the program would have potential for broader use. It could lead to significant
reductions in costs associated with poor school adjustment and mental health interventions later in a child's life.
Expected future outcomes:
It is expected that the results of this study will be disseminated through publication in a peer-reviewed referred
scientific journal.
Name of contact:
Email of contact:
Dr Margaret Brechman-Toussaint
Margaret.Brechman-Toussaint@qed.qld.gov.au
NHMRC Research Achievements - SUMMARY
University of New South Wales
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
157125
Prof Perminder S Sachdev
Geriatrics and Gerontology
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2001
2002
$150,950.00
Standard Project Grant
Title of research award: Risk and protection factors for normal and abnormal brain ageing: a longitudinal
epidemiological MRI study
Lay Description (from application):
Brain is considered the last frontier of medicine, and ageing the major challenge to health care in the 21st century.
In this proposal, we bring these two challenges together in a major new longitudinal study of ageing in Canberra
that has recently been initiated. This is a longitudinal study of a random community sample covering 3 age groups
- 20-24 years, 40-44 years and 60-64 years, with at least 2000 participants in each age group - who are being
assessed in 1999-2001, and will be followed up at 4-yearly intervals for 20 years. The focus of the study is on
neuropsychiatric disorders (anxiety, depression, substance use and cognitive disorders). In this application, we
propose to perform MRI scans and blood tests on a quarter (n=500) of the 60-64 sample to obtain an
epidemiological sample for brain morphology. Not only will we be able to study changes in brain morphology
over time, and relate it with cognitive function and psychiatric disorder, we will also be able to assess the role of
risk and protection factors. We are particularly interested in brain reserve, dietary factors (anti-oxidants, omega 3,
wine and folate) and drugs (anti-inflammatory drugs, hormone replacement and vitamin supplements) as
protection factors, and hypertension, homocysteine levels, white matter lesions on MRI and low hippocampal
volumes as risk factors for cognitive impairment and dementia. We also want to study the brain morphological
correlates of Depression in a community sample. The study will enhance our understanding of the ageing brain,
both in health and disease, and identify factors that increase or decrease the risk of cognitive impairment and
psychiatric disorder in old age.
Research achievements (from final report):
This grant was awarded to perform MRI scans on a random sample of 500 individuals in the age range 60-64
years who are participating in a longitudinal study of ageing (Path Through Life Project) being carried out by Prof
Tony Jorm and his colleagues in Canberra. It served as a baseline examination for future repeat scans, to be
performed in 4 years' time. Cross-sectional analyses were also planned to examine MRI parameters in a
community sample, and to relate them to cognitive function. The sampling began in March 2001 and MRI scans
commenced in May 2001, and was completed in August 2002. Of 637 participants so approached, 478 (75%)
(men = 252, women = 226) agreed to undergo an MRI brain scan. A further 35 subjects had MRI scans as they
were diagnosed with Mild Cognitive Impairment as part of the larger cohort (n = 2551). Data collection was
completed in 2002, and the data have been analysed and many publications have emanated from this study.
Further publications are planned. There were a number of other positive outcomes from this grant: i) A
neuroimaging lab has been set up in Canberrra at the Centre for Mental Health Research so that analysis can occur
concurrently in Canberra and Sydney. This lab has supported two PhD students who are nearing the completion of
their work; ii) The study was enhanced by obtaining blood samples from this cohort, which are being analysed in
various laboratories for neurochemistry, genetics and proteomics. A number of significant publications have
emerged from these analyses; iii) A collaboration has developed between our centres and the NICTA for the
development of image analysis software for advanced image analysis. iv) Many salient publications have emerged
from the study
Expected future outcomes:
This is the second largest community-based MRI study in the world and has a wealth of information. Wave 2 of
this study will occur in 2005-06 and will be funded from the Program Grant awarded to Professors Sachdev,
Brodaty & Andrews, and to Prof Jorm's group at the CMHR.
Name of contact:
Email of contact:
Prof Perminder Sachdev
p.sachdev@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
172310
A/Pr Maree R Teesson
Epidemiology
University of New South Wales
Start Year:
2001
End Year:
2002
Total funding: $430,264.00
Grant Type: NIDS Project - National Illicit
Drugs Strategy 26
Title of research award: Longitudinal outcome of treatment for opiate dependence: Addiction Treatment
Outcome Study (ATOS)
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The Australian Treatment Outcome Study (ATOS) is the first large scale longitudinal study of heroin users to be
conducted in Australia. ATOS recruited 615 participants entering the major treatment modalities for heroin
dependence in NSW (201 methadone/buprenorphine maintenance, 201 detoxification, 133 residential
rehabilitation) and a comparison group of 80 heroin dependent individuals not currently in treatment. At 3 and 12
months, 89% and 80% of the original sample where reinterviewed respectively. These follow-up rates are 10%
higher than that of similar studies undertaken internationally and demonstrate the feasibility of conducting
longitudinal research within this difficult popualtion. Of particular concern are the high rates of posttraumatic
stress disorder found among the sample (42%). In terms of outcome, those who entered treatment at baseline
showed substantial improvements in drug use, criminality, physical and mental health at 3 months, which were
maintained at 12 month follow-up. In contrast, there was comparatively little improvement among the nontreatment group. 14% of the sample achieved continuous heroin abstinence over 12 months, which was predicted
by greater treatment exposure and treatment stability over the follow-up period. As a natuaralistic study, one of
the major benefits of ATOS is that it has enabled the natural history of heroin users to be investigated, an area of
much needed research. The study has demonstrated that the provision of treatment in the 'real world' (as opposed
to artificial randomised treatment trials) substantially improves the health and welfare of heroin users. ATOS has
produced 8 technical reports, 5 peer reviewed published papers, 4 papers in press, 7 submitted papers, and 20
conference presentations.
Expected future outcomes:
Having demonstrated the feasibility and benefits of such longitudinal research, ATOS was further funded
(NHMRC 300454) to conduct 24 and 36 month follow-ups, and is seeking further funding to continue the study
beyond that time. The findings of ATOS also highlight issues that may have implications for treatment outcome.
Name of contact:
Email of contact:
A/Prof Maree Teesson
m.teesson@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
113844
Prof Stewart L Einfeld
Mental Health
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
1999
2004
$731,908.00
Standard Project Grant
Title of research award: Longitudinal Study of Behaviour and Emotional Problems in Young People with
Intellectual Disabilities
Lay Description (from application):
Families caring for young people with intellectual disabilities face major burdens of care if the young person also
has serious behaviour problems. These behaviour problems are also costly for our community. This project is
intended to assist young people and their carers by providing new information about the factors contributing to
these behaviour problems and how they develop over time. The project makes use of an internationally unique
follow up study which has followed a group of young people aged 4-18 for the last eight years. The young people
are now entering a critical age band facing many changes in their lives such as the possibility of independent
living, work challenges, as well as a search for new social relationships and day activities in the post-school
period. Also they face increased risk for mental health problems which most commonly emerge in this age group,
particularly psychosis and depression. This project promises to determine how the young people cope with these
challenges and what steps our community needs to make to assist them and their families to reach an optimal
adjustment.
Research achievements (from final report):
The Australian Child to Adult Development (ACAD) study is an internationally unique longitudinal study of
emotional and behavioural disturbances in young people with intellectual disability (ID). The ACAD study sample
consists of an epidemiological group and main syndrome groups (Fragile X, Prader-Willi, Williams, Down
syndromes and autism) which cover the full ID range (mild to profound) and are representative of urban and rural
communities in Australia. Almost eighty percent of the original participants have been followed for the last fifteen
years. The ACAD study has found that levels of psychiatric disturbances reduce as people move from adolescence
into adulthood. However, behavioural and emotional problems persist. Severity of ID influence both the level and
type of disturbance. That is, those with mild ID are more likely to have disruptive and antisocial behaviour
problems, while those with severe ID are more likely to engage in self-absorbed behaviours and have difficulty in
social relating. Protective factors and potential risks for emotional and behavioural problems in young people with
ID have also been investigated. These variables include the young person's temperament, life events, parent
mental health and family functioning. However, the genetic cause of ID is most influential on emotional and
behavioural disturbances. A greater understanding of the course, and causes of behavioural and emotional
disturbances has been achieved. These findings have implications for the diagnosis, intervention and prevention of
disturbance in young people with ID.
Expected future outcomes:
Further collaboration with national and international researchers. Increased understanding of biological and
psychosocial causes of emotional and behavioural disturbances in young adults with ID through the continuation
of the ACAD study.
Name of contact:
Email of contact:
Professor Stewart Einfeld
s.einfeld@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
209577
Start Year:
2002
CIA Name: Prof Reginald F Westbrook
End Year:
2004
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$270,000.00
Admin Inst: University of New South Wales
Grant Type: Standard Project Grant
Title of research award: Increased vulnerability to stress following opiate dependence: Molecular, anatomical,
and behavioural correlates
Lay Description (from application):
Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse
impact upon individual users, their families, and communities. It is a chronically relapsing condition for which
few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains
heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive
some individuals to start using heroin, stress increases the pleasurable effects of heroin and stress increases the
aversive effects of heroin withdrawal. These effects will encourage addiction and discourage addicts from seeking
treatment. Stress can also cause an otherwise drug-free individual to relapse to heroin addiction despite having
been drug-free for some time. In this project we will study why stress has such a large impact on heroin addicts
and heroin addiction. We will test the hypothesis that heroin use actually produces profound alterations in the
neural network in the brain which controls responses to stress. This project uses a simple animal model of heroin
addiction whereby rats are injected with morphine to study the regulation of several genes which are important in
responding to stress. We will also study how this exposure and changes in gene expression alter neurobiological,
cardiovascular, and behavioural responses to stress. This project will identify parts of the brain that are altered
during heroin addiction, and will also identify why heroin addicts are more vulnerable to stress than the general
population. Therefore, this project will help us to identify targets for therapeutic intervention (both psychological
and pharmacological) and possibly disrupt the addictive cycle.
Research achievements (from final report):
We made the novel discovery that there are bi-directional interactions between stress and opiate-dependence: just
as a history of stress leaves an organism more vulnerable to drugs of abuse, so too does a history of exposure to
drugs of abuse leave an organism more vulnerable to stress. This was a novel discovery. It was based upon work
studying gene expression changes in the rat brain as a consequence of exposures to drugs of abuse as well as
exmaination of behavioural and autonomic responses. We characterised this vulnerability to stress in terms of its
behavioural and autonomic sequellae as well the variables influencing its induction and persistence. This
discovery of a persistent increased vulnerability to stress is important because it suggests a principled reason as to
why stress is a potent trigger of cravings and relapse in abstinent addicts and because it offers novel ways of
thinking about, and potentially treating, the interaction between stress and drug dependence.
Expected future outcomes:
We expect that this work will influence future basic and clinical research, with a particular goal being the
translation of these findings into novel ways of of conceptualising and treating the interaction between stress and
drug dependence.
Name of contact:
Email of contact:
Dr. Gavan Mcnally
g.mcnally@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
209588
Prof Richard A Bryant
Mental Health
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$270,000.00
Standard Project Grant
Title of research award: Enhancing Treatment Effectiveness in Acute Stress Disorder
Lay Description (from application):
Posttraumatic stress disorder (PTSD) is the most common psychiatric condition to develop after trauma. Early
intervention of PTSD following a trauma is indicated because chronic PTSD can be resistant to treatment. Early
intervention is possible because acute stress disorder immediately after a trauma identifies those people who will
develop chronic PTSD. Although cognitive behaviour therapy of acute stress disorder can effectively prevent
PTSD in many cases, many people do not benefit from this treatment because this treatment involves exposure to
distressing memories and emotions, and this contributes to many people dropping out of treatment. This project
aims to extend the utility of early intervention following trauma by assessing approaches that can be used by most
trauma survivors. The project compares early intervention with either exposure, cognitive therapy, combined
exposure and cognitive therapy, or supportive counseling. All therapy will be conducted in the initial four weeks
and will comprise 6 sessions. Assessments will be conducted posttreatment, six-months follow-up, and one-year
follow-up. The outcomes of this project will have significant public health benefits because they will lead to
increased treatment effectiveness for acutely traumatized people, and will markedly reduce the incidence of PTSD
in the community.
Research achievements (from final report):
This major RCT of PTSD compared exposure therapy with a condition that included exposure therapy combined
with cognitive therapy. In contrast to several studies that possessed methodological limitations, this study
demonstrated that adding cognitive therapy to exposure therapy resulted in greater therapy outcomes six months
after treatment completion relative to exposure alone. This study has been published in the leading clinical
psychology journal (Journal of Clinical Psychology). In terms of impact, this is the first demonstration of the
clinical utility of combining these two interventions in reducing PTSD.
Expected future outcomes:
Future planned RCTs will try to enhance exposure by modifying the length of delivery of exposure.
Name of contact:
Email of contact:
Richard Bryant
r.bryant@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
157052
Prof Ian B Hickie
Psychiatry
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2001
2005
$500,000.00
Epidemiology
Title of research award: A prospective study of the psychiatric and medical characteristics of post-infective
fatigue and chronic fatigue syndrome
Lay Description (from application):
This project forms the central component of a larger set of studies which investigate competing psychiatric,
immunological and infective models of the causes of a number of chronic fatigue syndromes, including postinfective fatigue. The study takes place in western NSW where certain viral illnesses (Glandular Fever, Ross River
Virus) and a non-viral infection (QF) are common and have been associated with prolonged fatigue states. The
study follows patients from laboratory-documented infections with appropriate infective, immunological and
psychological measures throughout the course of their acute illness, the early recovery period and for the next 12
months. These patients are compared with people who present to their doctor with other forms of medicallyunexplained fatigue. Very few previous studies have used an appropriate prospective design and followed patients
with documented illness from the onset through to the development of specific forms of chronic fatigue. Further,
the study is unique in terms of the range of viral and non-viral agents being investigated. It relies on the combined
psychiatric, immunological and infective disease expertise of a group of researchers with an international
reputation for the successful completion of such multidisciplinary projects. The initial phase of the study has
demonstrated that the research team has the capacity to complete this project. Initial results have already
demonstrated the potential roles of psychological and immunological factors in causing some cases of prolonged
fatigue. Further, the initial results indicate that two key symptom sets (fatigue, psychological distress) can be
adequately measured during the recovery phase and are predicted by differing psychological factors. The study
will result in the identification of different psychiatric risk factors to chronic fatigue, assist development of clear
diagnostic guidelines for post-infective fatigue and guide relevant aetiological and treatment research.
Research achievements (from final report):
This study has identified that a post-infective fatigue syndrome is a common sequel of acute infection with
glandular fever, Ross River virus infection, and Q fever infection. The PIFS is very similar regardless of the
initiating infection, and features profound fatigue, muscle and joint pain, concentration and memory difficulties as
well as mood disturbance. PIFS persists in disabling degree in over one third of patients with these infections
when assessed at six weeks post onset, and in approximately 10% when assessed at six months post onset. At the
latter timepoint, the illness characteristics meet the diagnostic criteria for chronic fatigue syndrome (CFS). The
factors associated with the risk of developing CFS were examined - age, gender, perosnality type and prior
psychological disorder were not associated. Severity of the acute illness was the only significant predictor of the
subsequent development of CFS. The role of the initiating pathogen in driving the ongoing symptoms was
examined. No association between persistence of the organism and ongoing illness was identified. The role of the
host immune response against the infection in driving the ongoing illness was studied and similarly no evidence of
an abnormal ongoing immune response was found. The research has established the PIFS as a unique and
informative model for studies of the disease mechanisms underling CFS.
Expected future outcomes:
Genetic risk factors and gene expression correlates of the PIFS are being studied
Name of contact:
Email of contact:
Professor Andrew Lloyd
a.lloyd@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
222754
A/Pr Skye McDonald
Health, Clinical and Counselling Psychology
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$240,000.00
Standard Project Grant
Title of research award: Enhancing treatment effectiveness for psychosocial disorders after severe traumatic
brain injury
Lay Description (from application):
Motor vehicle accidents are a major cause of severe traumatic brain injury (TBI) leading to lifelong, crippling
disability. In NSW alone, there are approximately 770 new cases of severe brain injury each year. These people
require extensive inpatient rehabilitation and many go on to rely upon community resources for the rest of their
lives. The social and economic cost of such injury is cumulative. TBI is mainly experienced by young adults (1824 years of age) who have normal life expectancy and each year more casualties are added to this social burden.
Adults with TBI frequently experience a reduction in social skills. Loss of social skills presents major obstacles to
reintegration into the community by making the sufferer more taxing and less rewarding to interact with socially.
This loss of social skills limits their ability to maintain pre-injury relationships, and often creates an off-putting
"first impression" on potential new acquaintances that interferes with their ability to establish new relationships.
The following project is designed to develop and evaluate a treatment program to enhance the TBI individual's
ability to create a good "first impression" on meeting new acquaintances - e.g., potential employers, work
colleagues, customers, and social acquaintances - and to engage in behaviour that is mutually rewarding. The
project will inform current theoretical approaches to remediation, providing an examination of the modifiability of
social skills deficits that are the result of underlying cognitive impairments. It will provide a systematic, integrated
social skills treatment approach for both individuals and groups where there are currently very few. The
identification and refinement of successful treatment techniques will increase the efficiency of brain injury
rehabilitation in Australia, improve the quality of life for sufferers of TBI and their families, reduce cost of
rehabilitation and reduce reliance upon community resources in the long term.
Research achievements (from final report):
This project evaluated a new, three pronged approach to improving the social skills of adults with severe, chronic
brain injuries sustained as a result of trauma (e.g. motor vehicle accidents). Such injuries often cause difficulties in
cognition and behaviour and lead to longer term problems with social isolation, loss of self esteem, depression and
anxiety. To address this we developed a treatment program that included social skills training, remediation of
problems with social perception (e.g. reading emotions in others) and psychological treatment for individual
problems with self-esteem anxiety etc. This study used a randomised controlled trial and recruited 51 participants
who were allocated to treatment, social group (control condition) or waitlist. The program included 12 weekly 3
hour group sessions and individual sessions with a clinical psychologist. It was shown that treatment did improve
social behaviour and social perception in those who received treatment relative to those who remained on waitlist
or who participated in a social group without specific therapeutic content. Three manuals have been developed for
clinical use: (1) a social skills treatment manual (2) a social perception treatment manual (3) a manual for treating
social anxiety. The results of the trial have recently been prepared for publication. This is the first time a
comprehensive treatment for social skills for people with traumatic brain injuries has been evaluated and proven to
be effective. It paves the way for better, evidence based techniques in this much needed area of psychosocial
rehabilitation.
Expected future outcomes:
This research will improve remediation of social skills in people with brain injuries and lead to better use of
evidence based practice. It will also be an impetus for further research into techniques to improve psychosocial
function in this and other clinical groups.
Name of contact:
Email of contact:
Professor Skye Mcdonald.
s.mcdonald@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
222842
Prof Perminder S Sachdev
Psychiatry
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$459,500.00
Standard Project Grant
Title of research award: An extended follow-up of stroke patients for cognitive impairment and neuropsychiatric
disorders: Sydney Stroke Study
Lay Description (from application):
Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may
be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which
has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of
early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD
as defined by modern criteria has not been studied. There have been few studies of the progressive changes in
MRI in patients with cerebrovascular disease. The overlap of VaD and Alzheimer's disease (AD) remains a
problem for taxonomists and clinicians. One approach to the study of VaD is to examine a high risk group of
subjects longitudinally to determine the early features, the risk factors and progressive changes. With this in mind,
we began studying a cohort of stroke patients who are at high risk of VaD, in 1997-1999, and are following them
longitudinally. The follow-up is now in its third year, and three neuropsychological assessments and two
MRI/MRS scans have been performed. We propose to extend the follow-up to 5 years, with repeat
neuropsychiatric, neuropsychological and MRI/MRS investigations, and wherever possible to necropsy, to
determine the nature of vascular pathology that underlies cognitive impairment. Our cohort of stroke patients is
arguably the most comprehensively assessed such cohorts internationally, and presents an excellent opportunity
for a long-term follow-up study.
Research achievements (from final report):
This grant enabled us to follow up a cohort of stroke pateints for 5 years after the index stroke. In the earlier stages
of this study, funded by prevous NHMRC grants, we demonstrated that vascular dementia (VaD) and vascular
mild congitive impairment (VaMCI) are common in this cohort. In the extended follow up, we demonstrated that a
significant proportion of these subjects show progressive decline in their cognitive function, even in the absence
of further strokes. One of the factors that may account for this worsening is an increase in small vessel disease, as
shown by white matter hyperintensities (WMHs) on MRI. Some of the risk factors of WMHs are hypertension,
diabetes, low lung capacity and high homocysteine, all of which are partially correctable. Stroke pateints do not
have smaller hippocampi than control subjects, and the volume decreases over 3 years of follow-up, at about the
same rate as controls. The occurrence of further stroke or TIA leads to greater cognitive worsening. High lifetime
mental activity is protective against such worsening. Individuals with high lifetime mental activity have less
decline in hippocampal volumes. Magnetic resonance spectroscopy (MRS.) can be used to distinguish between
stroke patients with and without cognitive imapirment. MRS. at baseline is also a predictor of decline in the
future. Depression and apathy are common in patients with stroke, with rates of depression peaking at the 1 year
follow-up.
Expected future outcomes:
This cohort is now being followed up by telephone contact and mailouts. A significant proportion has signed in
for brain donation. This will help confirm the neuropahtology, especially to determine what proportion of those
with dementia have Alzheimer pathology.
Name of contact:
Email of contact:
Perminder Sachdev
p.sachdev@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
222849
A/Pr Tony G Butler
Epidemiology
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$195,000.00
Standard Project Grant
Title of research award: An examination of the causes of mortality following imprisonment in New South Wales
using data-linkage.
Lay Description (from application):
Prisoner populations are characterised by poor health status including infectious diseases, injury, risk taking
behaviours (eg. smoking and self-harm), mental illness, and substance abuse. Serosurveys of blood borne viruses
such as hepatitis C and hepatitis B conducted in Australian and overseas prison settings have found that over one
third of inmates have been exposed to these viruses with higher rates detected in injecting drug users and female
inmates. Few attempts have been made to examine the causes of mortality among prisoners following release from
detention. Most interest has focused on overdoses in the period immediately following release; the aim of this
study will examine all causes of death among individuals exposed to the correctional environment and compare
these to death rates for NSW. Correctional centres house a largely male (94% in NSW) population with
backgrounds of disadvantage in all areas, including Indigenous Australians, people of lower socio-economic
status, those with a mental illness, and the intellectually disabled. There are currently over 21,000 (June 2001)
prisoners detained in Australian correctional centres with approximately 39% housed in NSW. Fifteen percent of
the NSW prisoners are Indigenous but comprise only 2% of the general population. The aims of this project will
be to: (1) Identify all causes of death among ex-prisoners in NSW for the period 1985 to 2001; (2). Compare death
rates in the study group with those in the NSW community; (3) Correlate pre-release health information contained
in medical records with specific causes of death; (4) Compare causes of mortality among various sub-groups eg.
injecting drug users, the mentally ill, violent offenders, and the intellectually disabled; (5) Examine causes of
mortality between Indigenous and non-Indigenous inmates; and (6) use this information to develop pre-release
programmes aimed at reducing excess mortality among this group.
Research achievements (from final report):
This project is significant in that it has added to the body of evidence suggesting that prisoners are at a greater risk
of death (compared with the general community) for a range of health conditions, particularly drug overdose,
suicide, and homicide. Further, this study has identifed that those with a mental illness are at an extreme risk of
death from suicide and drug overdose.
Expected future outcomes:
Based on the unacceptably high death rate among those leaving the correctional system from drug overdoses,
discussions have been held with oversease researchers regarding the development of a multi-country RCT of
Naloxone distribution on release. Other intervention studies are also anticipated.
Name of contact:
Email of contact:
Tony Butler
tony.butler@justicehealth.nsw.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300454
A/Pr Maree R Teesson
Psychiatry
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2004
2005
$411,500.00
Standard Project Grant
Title of research award: A prospective cohort study of mortality, abstinence, criminality and psychiatric
comorbidity
Lay Description (from application):
Over 70 000 Australians are dependent on heroin. Heroin dependence is remarkably persistent and is, in many
cases, a lifelong condition. Long term treatment outcome and abstinence from heroin among this group are poor.
Mortality among heroin users is high, with heroin users dying at a rate 13 times that of peers. Despite the extent of
the problem, the natural history of heroin users has not yet been studied in Australia. The current study will be the
first Australian study of the natural history of heroin users. The study will follow up a large cohort of heroin users
over a three year period. Estimates will be obtained of mortality rates, abstinence rates, criminal careers, and
psychiatric problems among heroin users. It will also examine factors that predict abstinence, mortality,
criminality and levels of psychopathology, and determine the health costs associated with heroin use careers. The
study will provide essential data on how heroin use progresses, and on what factors predict a better outcome for
heroin users.
Research achievements (from final report):
The study examined the impact of treatment on drug use, injection-related risk taking, criminality, and general
physical and mental health over 3 years among heroin dependent Australians. The cohort of heroin users
established as part of the Australian Treatment Outcome Study (ATOS), the first large scale longitudinal study of
heroin users to be conducted in Australia, was followed up at 2 and 3 years post entry to the ATOS study. The
initial cohort consisted of 615 participants entering treatment for heroin dependence in NSW (201
methadone/buprenorphine maintenance, 201 detoxification, 133 residential rehabilitation) and a comparison group
of 80 heroin user not currently in treatment. At 2 and 3 years, 76% and 70% of the original sample were
reinterviewed respectively. These follow-up rates are of an international standard and demonstrate the feasibility
of conducting longitudinal research within this difficult population. At 3 years, there were impressive reductions
in drug use, criminality, psychopathology and injection-related health problems following treatment exposure.
Importantly there was no evidence for drug substitution in the face of reduced heroin use. Despite substantial
improvements in psychological distress, the mental health of the cohort remained substantially worse than that of
the general population, with comparatively high levels of PTSD and suicidality. As a naturalistic study, one of the
major benefits of ATOS is that it has enabled the natural history of heroin users to be investigated. Of clinical
importance was the finding that stable retention in treatment was a consistent predictor of superior treatment
outcome.
Expected future outcomes:
As heroin use is a disabling, and often lifelong condition, the factors associated with maintaining positive
treatment outcomes, and preventing relapse require longer term follow-up. Funding for an 8 year follow-up will be
sought. Addititional funding has been obtained to develop an integrated intervention package for PTSD and
substance use disorders.
Name of contact:
Email of contact:
Maree Teesson
m.teesson@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300471
A/Pr Jan Copeland
Health, Clinical and Counselling Psychology
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2004
2005
$208,125.00
Standard Project Grant
Title of research award: A multisite randomised controlled trial of the Adolescent Cannabis Check-up
Lay Description (from application):
Recent Australian surveys cannabis use is more common than tobacco use among 14-19 year old (24.6% vs.
20.2%). More than 200,000 14-19 year olds have used cannabis in the last month and 7.1% report daily use. The
population prevalence of cannabis dependence increases throughout adolescence, with a rate of 30% among those
who use cannabis more than five times per year. Although experimentation is a normal part of adolescent
development, regular cannabis use by young people exposes them to the negative effects of cannabis at a time of
rapid development and transitions in life roles. There have been no studies reported of interventions suitable for
adolescents with cannabis problems who are not seeking treatment but are causing great concern for their families,
schools and communities. The Adolescent Cannabis Check-up (ACCU) fills this serious gap by providing
adolescents with an opportunity to objectively assess their cannabis use and develop strategies for change in a
non-judgemental environment. The ACCU is a 2 session intervention: assessment and a follow-up session of
personalised feed-back and brief skills-based therapy. Recruitment may be either direct or via a concerned family
member. This novel approach provides parents with telephone coaching, and supporting booklets, on techniques
to encourage their young person to participate. A feasibility study of 80 families has found more than 50% were
able to do so. That study of 55 adolescents found a significant reduction in levels of cannabis use and an
abstinence rate of 24.2% 3 months following participation in the ACCU. This project wll involve a multi-site RCT
to compare the impact of the ACCU with a delayed treatment control group, on levels of cannabis use,
dependence, and cannabis-related problems. This project would fill a gap in treatment service models and involve
families in an initiative to assist young people to develop motivation and skills to abstain from problematic
cannabis use.
Research achievements (from final report):
This study provides a novel intervention that targets young people who use cannabis. A treatment manual has been
produced which is available to front-line workers in the drug and alcohol treatment field. The study itself has
demonstrated the effectiveness of the intervention in reducing cannabis use, and can thus be used with confidence
by clinicians. Potential benefits relate to having a demonstrably effective programme for reducing cannabis use
among young people.
Expected future outcomes:
Future outcomes will involve dissemination of ther intervention, and possibly development of novel forms of
treatment delivery, including web-based delivery
Name of contact:
Email of contact:
Greg Martin
g.martin@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300432
Prof Mark Dadds
Psychiatry
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$335,000.00
Standard Project Grant
Title of research award: Behavioural and neuropsychiatric aspects of transition to severe conduct disorder in
adolescence
Lay Description (from application):
Conduct disorder represents an enormous cost to Australian society directly via the mental health and forensic
systems, and indirect costs via its associations with other mental health problems, relationship problems, impaired
social functioning, and substance use problems. Behavioural-family-based treatment have good success rates with
young children with cooperative parents, however, there are a minority who progress to chronic problems despite
this. Risk and resilience factors identifying chronic patterns in early childhood are the key to early intervention. In
previous research, this research team showed for the first time that callous-unemotional traits, a feature of chronic
psychopathy, could be measured in children as young as 4 years, and was predictive of a range of negative
outcomes. However, it was also found that the key neuropsychiatric markers characteristic of psychopathy,
including reward dominance/punishment insensitivity and deficits in affective empathy, did not exist in conduct
problem children prior to adolescence. Around the time of puberty, it appears that important changes occur in
cognitive/affective processing styles that are associated with the "adult" form of psychopathy and antisocial
behaviour. Thus, this research raises critical questions about the development of severe antisocial behaviour (or
psychopathy) through the childhood to adolescent years. Our evidence indicates that early adolecence may be the
period when intrapsychological characteristics representing chronic risk become concrete. The current research
will be the first to map the development common neuropsychiatric markers (affective empathy, punishment
insensitivity) of severe antisocial processes through the late childhood-adolescent period. The findings will have
clear implications for models of antisocial behaviour and clinical approaches to working with conduct problem
children and adolescents.
Research achievements (from final report):
This research impliciated specific emotion-processing mechanisms in the persistance of antisocial behaviour
across childhood and adolescence, and demonstrated that these risk-mechanisms are amenable to intervention.
Expected future outcomes:
Development of new forms of early intervention for children at risk for antisocial behaviour and related
psychopathology.
Name of contact:
Email of contact:
Mark Dadds
m.dadds@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
222708
Prof Gordon B Parker
Psychiatry
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2003
2007
$7,700,000.00
New Program Grant
Title of research award: Depressive and Bipolar Disorders: Evaluating Determinants of Onset, Recovery and
Treatment Resistance
Lay Description (from application):
The depressive disorders, including bipolar disorder, are highly prevalent in the Australian community. These
illnesses may be chronic or relapsing, may impair the capacity to work and can be resistant to treatment. The
research team addresses this public health and clinical problem by undertaking a number of studies pursuing
factors influencing predisposition and onset to disorder, clarifying the effectiveness of new treatments, and
investigating factors predictive of treatment response and resistance.
Research achievements (from final report):
Mood disorders are commonly classified by severity, largely ignoring causes and leading to limited treatments.
The Team clarified how differing depressive and bipolar (mood) disorders are best modelled and pursued their
differing causes, so assisting identification of specific treatments relating to their underlying causes. Our studies
employed a range of sophisticated technologies, including molecular biology, brain imaging techniques, and
mathematical modeling. Some studies involved reviews of established treatments (e.g. cognitive behaviour
therapy and interpersonal psychotherapy for depression), others of new treatments (i.e. the role of omega-3 fatty
acids for mood disorders). Many studies reflected a commitment to a research paradigm that weights clarification
or modification of the 'model' for distinguishing mood disorders, then pursuing underlying neurobiological
mechanisms (including gene-environment linkages), and then moving to translational research (which informs
clinical management).
Expected future outcomes:
The Team continues the general themes from above, with a distinct focus on modelling the bipolar and depressive
(mood) disorders; testing the importance of categorical models over traditional dimensional models is emphasised.
Name of contact:
Email of contact:
Professor Gordon Parker
g.parker@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
231408
Prof Mark Dadds
Mental Health
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2003
2007
$0.00
NHMRC Research Fellowship
Title of research award: Research Fellowship SRFB
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
This research idenitified markers of serious risk for behavioural and emotional disorders in children, as well as
factors that predict poor response to existing treatments. Several novel strategies for early intervention with these
children were also identified.
Expected future outcomes:
Development of new forms of early intervention for children with risk for serious emotional and behavioural
problems.
Name of contact:
Email of contact:
Mark Dadds
m.dadds@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300443
Prof Susan C Kippax
Health and Community Services
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$295,125.00
Standard Project Grant
Title of research award: Comparing the role of takeaways in methadone maintenance treatment in New South
Wales and Victoria
Lay Description (from application):
This project will make a direct and major contribution to improving methadone maintenance treatment (MMT)
provision in Australia. The recent announcement of the continuation of funding for the Federal Government's
Illicit Drug Diversion Initiative demonstrates an ongoing commitment to make drug treatment programs more
accessible. MMT is currently the primary treatment for opioid addiction in Australia. However, concerns about the
potential negative effects of aspects of the programs, in particular, takeaway dosing and diversion of methadone to
street sale (which has been linked to accidental fatal overdose (Lintzeris, et al., 1999)), remain unresolved. This
study will map clients', healthcare workers' and policy makers' attitudes towards takeaways in NSW and Victoria,
and investigate the dynamics of methadone diversion in relation to the different takeaway policies in the two
states. In doing so, the project will consider how the two different state policies on takeaways stack up. It will
contribute essential and detailed data on takeaways and diversion, from which effective, safe and socially
responsible methadone maintenance treatment policy can be developed.
Research achievements (from final report):
This project generated new knowledge on methadone treatment delivery, the experiences of clients in treatment
and the causes and circumstances surrounding medication diversion. The project attracted a great deal of interest
among service providers and policy makers and was the subject of invited keynote presentations, as well as a
dedicated session at APSAD 2006. The project produced a well-received report and book, as well as a range of
well-received journal articles
Expected future outcomes:
Project will impact on policy around treatment delivery in NSW and Victoria and will form the basis for a future
study on families and pharmacotherapy.
Name of contact:
Email of contact:
Dr Suzanne Fraser
suzanne.fraser@arts.monash.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300538
Prof Reginald F Westbrook
Central Nervous System
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$234,250.00
Standard Project Grant
Title of research award: Inhibition of fear memories by extinction: neural substrates
Lay Description (from application):
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology
in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and
autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the
emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in
the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories
can be inhibited or suppressed. Understanding this latter process is a key to the development of effective
treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted
trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject
to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or
extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due
to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the
fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the
fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s)
in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the
expertise of four well-established researchers and uses a combination of behavioural, physiological,
immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will
reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the
fear pathway
Research achievements (from final report):
Clinical trials have established the effectiveness of cognitive-behavioural therapy in treating anxiety disorders
such as post-traumatic stress. A component of this therapy involves the patient confronting trauma-related cues in
the absence of any overt danger. The aim of these confrontations is to inhibit the ability of the cues to elicit the
fear that undermines the quality of the patient's life. This project proposed to use an animal model (i.e., extinction
of conditioned fear) to identify the neural mechanisms that underlie this inhibition. We found that the basolateral
complex of the amygdala and the infralimbic subregion of the medial prefrontal cortex are critical for learning to
inhibit conditioned fear in extinction. Importantly, we have shown that these regions contribute to the formation of
that inhibition in a distinct and specific manner. Finally, we found that D-cycloserine, a partial agonist of NMDA
receptors, facilitates the development of inhibition in extinction. These findings are critical for the establishment
of new pharmacological targets aiming at improving the success of cognitive-behavioural therapy in treating
anxiety disorders.
Expected future outcomes:
We are actively pursing this project by focusing our effort on the mechanisms that lead to a return of fear after
extinction. For instance, extinguished fear can be restored by various manipulations that include a shift in context
or the elapse of time. This research has major clinical implications as cognitive-behavioural therapy is also
sensitive to such manipulations.
Name of contact:
Email of contact:
Fred Westbrook
f.westbrook@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
325643
Dr Janice M Fullerton
Neurogenetics
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2006
2007
$104,687.00
Howard Florey Centenary
Title of research award: Howard Florey Centenary
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Bipolar disorder is a relatively common and highly debilitating mood disorder, which affects up to 4% of the
population. Relatives of individuals with bipolar disorder share an increased risk for developing the illness,
compared to the normal population risk. It is thought that this is caused by genetic factors which are inherited
through transmission of DNA through the family, however no specific genetic causes have yet been identified.
This failure to identify specific genetic risk factors may be a result of over-simplifying the disorder, in: 1) its
clinical symptoms and 2) the pattern of inheritance of genetic factors through a family. In this study, I designed a
questionnaire to identify individuals who do not exceed clinical thresholds for diagnosis of bipolar disorder, but
who show moderate mood disturbance, and hence may provide a more accurate tool for following transmission of
genetic risk factors than clinical diagnosis. The responses showed a significant difference between individuals
with bipolar disorder and those without, however did not show a difference between bipolar relatives and normal
controls, hence is no more informative than a clinical diagnosis. I also applied a complex genetic model to follow
genetic transmission through 65 large Australian families with bipolar disorder, allowing for analysis of genetic
interactions and multiple genetic risk factors. This analysis revealed four regions in the genome which likely
contain genetic factors which act independently, and six regions which contain genetic factors which contribute to
genetic risk when inherited together. These regions are under further investigation.
Expected future outcomes:
We are currently using the results of our analysis of the genetic transmission of bipolar disorder to identify
specific bipolar risk genes in which lie in the regions identified through this project. This work will ultimately lead
towards better treatments for individuals with bipolar disorder.
Name of contact:
Email of contact:
Anne Graham
a.graham@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
350879
Start Year:
2005
CIA Name: Dr Gavan P McNally
End Year:
2007
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$389,750.00
Admin Inst: University of New South Wales
Grant Type: Standard Project Grant
Title of research award: Contextual control over relapse to drug-seeking: behavioural and neural mechanisms
Lay Description (from application):
Drug addiction is a major health and societal problem in Australia. It is consistently associated with an adverse
impact upon individual users, their families, and communities. Prolonged drug use is associated with increased
rates of physical problems (e.g., cardiovascular disease), mental health problems (e.g., depression and anxiety),
and criminal involvement (e.g., property crimes and incarceration). A defining feature of drug addiction is that it
is a chronically relapsing condition. Between 60-80% of addicts attempting to "give up" drug taking will relapse
to drug taking. The behavioural and brain mechanisms which underpin this persistent propensity to relapse are
largely unknown. This project studies the behavioural and brain mechanisms for relapse to drug addiction. This
project uses a well validated animal model of drug taking to ask why relapse occurs. It will identify some of the
environmental antecedents to relapse and the brain mechanisms which mediate relapse. As such, this project will
project will provide important information about relapse to drug addiction and may help identify targets for
therapeutic intervention and possibly disrupt the addictive cycle.
Research achievements (from final report):
This project studied how the brain controls relapse to drug-seeking after a period of abstinence. The chief focus
was specifically on how the contexts and places associated with drug-taking elicit such relapse. The project
studies how the brain mechanisms for such relapse were similar and different across three different kinds of drugs
and rewards: psychostimulants; alcohol; and a natural reward sucrose (sugar). We showed that a common brain
ciruit mediates relapse to seeking these three rewards but that different molecules within these circuits are
important for relapse to seeking the different rewards.
Expected future outcomes:
The project will have influence on future basic science research mapping the brain mechanisms for relapse. It is
the goal of this research to identify new ways of helping drug users achieve long-term abstinence.
Name of contact:
Email of contact:
Gavan P. Mcnally
g.mcnally@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
350963
Dr Adam J Guastella
Health, Clinical and Counselling Psychology
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$400,750.00
Standard Project Grant
Title of research award: D-Cycloserine And Conditioning: Increasing The Effectiveness Of Exposure Therapy
For Fear And Anxiety
Lay Description (from application):
The psychological, social, and financial costs of anxiety problems are among the highest burden-of-disease costs
to the community. The most effective long-term psychological treatment for anxiety disorders is cognitive
behaviour therapy (CBT), in particular exposure therapy. However only a small minority of individuals receive
comprehensive treatment, and a portion of these individuals re-experience symptoms in the long-term. These
difficulties are partially due to the cost of treatment and difficulties with relapse. Recent research has shown that
D-Cycloserine (DCS) facilitates extinction in animals and possibly in humans. DCS has the potential to offer a
simple, brief, and cost-effective intervention that enhances treatment effects. In the United States the new NIMH
director has set research into DCS and exposure to fear as a high priority that is likely to have a significant public
health impact. This proposal provides an opportunity for Australian researchers to become involved in a rapidly
expanding research field. The research team at UNSW have already established an international reputation in DCS
applications, fear conditioning in humans, and clinical trials in humans. They are in a unique position
internationally to investigate the means by which DCS exerts its effects and to conduct randomised clinical trials
of DCS in recovery from fear in humans.The goal is to test DCS in facilitating exposure and extinction of fear.
The research will directly lead to recommendations for clinical application and demonstrate whether the drug has
the capability of significantly increasing the success of exposure therapy by reducing the time required for
treatment, the rate of relapse, the financial cost of treatment, and the overall burden of anxiety to the community.
The fear-conditioning studies will also inform our theoretical understanding of emotion processing and fear
conditioning in humans, which in turn will allow clinical applications to be optimised.
Research achievements (from final report):
This project showed that a simple, low-cost antibiotic, d-Cycloserine (DCS), could enhance the treatment os
exposure therapy for Social Anxiety Disorder if administered immediately before psychological therapy sessions.
The antibiotic was suggested to enhance learning during therapy. Patients who were administered DCS show a
greater reduction in anxiety symptoms in the long term and a lower rate of relapse in comparison to patients who
received a placebo. In terms of mechanisms, our research led to the publication of 5 randomized controlled trials
in non-clincial populations to determine the influence of DCS on pavlovian fear conditioning. These studies failed
to show any influence of DCS on overcoming in non-clinical populations. This research suggests that the effects
of DCS may be specific to clinical levels of fear.
Expected future outcomes:
This research has laid the evidence base to apply DCS to different populations and to integrate treatment into the
community.
Name of contact:
Email of contact:
Adam Guastella
aguastella@med.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300403
Prof Richard A Bryant
Psychiatry
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2004
2008
$477,000.00
New Program Grant
Title of research award: Posttraumatic Mental Health: Enhancing Resilience and Recovery
Lay Description (from application):
Psychological disorders following exposure to trauma account for a significant proportion of the burden of disease
in terms of personal suffering, decreased productivity, occupational and social dysfunction, medical disorders, and
demands on health services. The overall goal of this project is to enhance the nation’s capacity in research into the
identification of risk factors for posttraumatic mental disorders, study of neurophysiological factors mediating
these disorders, and evaluation of treatment strategies to reduce psychological morbidity after trauma. This project
will develop a critical mass of Australia’s leading trauma researchers that will ensure that Australia retains its
leading edge in posttraumatic research.
Research achievements (from final report):
The research undertaken in this Program has made many seminal advances in the understanding, prevention, and
treatment of psychological effects of trauma. These achievements include: 1. We conducted the largest multi-site
prospective study ever undertaken after trauma. This study addressed core scientific questions about the nature of
posttraumatic adjustment that previous studies have not been able to address. By incorporating 5 sites, we
overcame the obstacles of single-site studies that have limited the field to date. This study identified core risk
factors that have led to screening tools to identify people at high risk after trauma. 2. A large-scale
epidemiological study conducted in Vietnam interviewed 3.000 Vietnamese in rural villages in Vietnam to assess
the mental health impact of a long series of conflict and war on these communities. This study was pivotal in
highlighting how western measures of mental health can underestimate the prevalence of disorders relative to
indigenous measures. 3. The Program showed for the first time the neural markers of positive response to
treatment for posttraumatic stress disorder 5. The Program also completed a seminal study that demonstrated the
optimal means to prevent PTSD through early intervention after trauma.
Expected future outcomes:
This Program is continuing in a successful reapplication of the Program (2010-2014), which is focusing on more
sophisticated subtypes of posttraumatic response, better treatment strategies, and adapting our evidence base to
nonwestern settings.
Name of contact:
Email of contact:
Professor Richard Bryant
r.bryant@unsw.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
376011
Prof Peter R Schofield
Cellular Nervous System
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$374,250.00
Standard Project Grant
Title of research award: The biological role of the cadherin gene FAT in bipolar disorder susceptibility
Lay Description (from application):
Bipolar disorder (manic depressive illness) is a severe mood disorder, with a lifetime prevalence of up to 1%. The
illness is characterised by aberrant mood swings resulting in periods of mania and depression with reversion to
normal behaviour between episodes. The condition has a severe impact on sufferers, being demonstrated to be the
sixth most disabling disorder in the WHO Global Burden of Disease report and increasing the risk of suicide
fifteen-fold. There is a pressing need to define more clearly the biological basis of bipolar disorder as a necessary
prerequisite to improved diagnosis and treatment. The underlying causes of bipolar disorder remain unknown.
However, family studies reveal the high heritability of bipolar disorder and this familial clustering provides an
opportunity to use genetic approaches to identify the predisposing genes. The long-term aim of our research is to
investigate the biology of those genes that either cause or predispose to bipolar disorder. We have previously used
genetic approaches to identify the first bipolar disorder susceptibility gene, a cell contact molecule located on
chromosome 4 that is from the cadherin family. The aim of this proposal is to understand how this gene
contributes to the risk of developing bipolar disorder. This will be achieved by identifying how the cadherin
susceptibility gene, termed 'FAT' results in altered properties in laboratory assays or in altered behaviours in
animal models. Identifying the genes responsible for bipolar disorder and understanding their contribution to the
biological basis of this severe psychiatric condition is essential to translate these discoveries into improvements in
the ability to diagnose, treat and prevent the illness.
Research achievements (from final report):
Despite being highly heritable, the underlying biological cause of bipolar disorder remains largely
unknown. The identification of specific genetic risk factors will provide a means by which the cause of this
devastating mental illness can begin to be defined. Evidence from positional cloning, association analysis, and
expression studies led to the identification of the protocadherin gene FAT as a bipolar susceptibility gene. We
examined genetic variation in the region surrounding the strongest single point association in FAT and the
adjacent MTNR1A (melatonin receptor 1A) gene. We identified two regions of association, one including the
promoter of the MTNR1A gene, and one in the FAT gene. Resequencing subject DNA spanning these regions has
identified variation which is uniquely present in bipolar patients. Analysis of brain samples with and without the
"risk" variants at both FAT and MTNR1A suggests that both regions significantly affect transcription of the
downstream MTNR1A gene suggesting that the disease risk occurs by reduction in MTNR1A expression.
Additional linkage analysis gave evidence that the FAT/MTNR1A locus interacts with a locus on chromosome
1p36 giving a further insight into the molecular pathways through which the gene operates.
Expected future outcomes:
The current studies have provided a new insight into the specific genetic risk factors that may predispose to
bipolar disorder. This work will lead to a better understanding of the causes of this illness, a necessary prerequisite
for better diagnosis and treatment.
Name of contact:
Email of contact:
Prof Peter R Schofield
p.schofield@powmri.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
351020
Prof Susan C Kippax
Primary Health Care
University of New South Wales
Start Year:
End Year:
Total funding:
Grant Type:
Research Grant
2006
2009
$470,290.00
General Practice Clinical
Title of research award: Prevalence, nature and recommendations for clinical management and self-management
of depression for people with HIV
Lay Description (from application):
By comparing the nature and prevalence of depression in those with and without HIV, and documenting the ways
in which general practitioners manage depression in their patients, the project will provide a comprehensive and
layered understanding of depression among men, particularly those living with HIV in urban and regional
Australia. Project findings will develop the skills and research capacity of general practitioners in the assessment
and management of depression.
Research achievements (from final report):
The study found that among men accessing urban general practices, gay self-identified men were more likely to
suffer from major depression than men in the general population. Nearly 25% who attended the four high HIVcaseload general practices in Sydney and Adelaide and completed the depression screening questionnaire had
major depression at the time of the survey. The key social factors independently associated with a current episode
of major depression among gay men, based on the PHQ-9 self-screening tool, included: younger age, lower
income, recent major adverse life events, adopting denial and isolation as ways to cope with stress, less social
support, less gay community involvement, and recent sexual difficulties. While significantly more HIV-positive
gay men suffered from major depression (30%), HIV-status was not independently associated with major
depression. The high rates of depression among both HIV-positive and HIV-negative gay men are likely to be
related to the marginalisation and discrimination experienced by gay men. General practitioners (GPs) working in
high HIV-caseload general practice settings in Australia have a heightened awareness for detecting depression in
gay men which is demonstrated in a high level of concordance between GP assessments and patient screening for
depression. These findings have informed the development of a new module for the self-management of
depression for gay men, hosted on the ClimateGP website and the development or revision of case studies and
other materials used by the Australasian Society for HIV Medicine in education and training programs for s100
GP prescribers.
Expected future outcomes:
Additional articles are in preparation for submission to peer reviewed journals and conference papers will be
presented in October 2009. An online module has been developed for use by ASHM in their program of
continuing medical education for GPs who are accredited to prescribe HIV medications, and we hope that with
time there will be some evidence of the uptake and usefulness of this tool.
Name of contact:
Email of contact:
Susan Kippax
s.kippax@unsw.edu.au
NHMRC Research Achievements - SUMMARY
University of Newcastle
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
100967
A/Pr Amanda L Baker
Psychiatry
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2000
2002
$217,465.00
Standard Project Grant
Title of research award: Evaluation of cognitive-behaviour therapy for alcohol and other drug problems among
people with a psychotic illness
Lay Description (from application):
Abuse of alcohol and other drugs among people with a major psychiatric illness is a serious public health problem
and cost-effective treatments need to be developed and assessed. The aim of this project is to evaluate the
effectiveness of a counselling intervention. 180 individuals with a psychotic illness and concurrent alcohol and
other drug (AOD) problems will be randomly assigned to counselling or usual treatment and followed up for a
period of 12 months. The indicators of interest include: current drug use; psychiatric symptoms; self-harm; social
functioning; and use of health services. Findings from the proposed study will assist in the selection of particular
treatment strategies and will aid the overall development of services for people with both major mental illness and
substance abuse.
Research achievements (from final report):
This trial has led to significant advances in research design for people with co-occurring psychotic illness and
drug and alcohol problems. It has highlighted the co-occurrence and treatability of the specific co-occurring
condition of cannabis and psychosis and has indeed seeded a further postgraduate research project in this area. It is
important that the treatment offered in this trial be transferred into routine clinical practice, particularly among
cannabis users who have a psychotic condition. The treatment evaluated in this trial offered an integrated
approach, where mental health problems (psychosis) and drug and alcohol use were addressed within the one
framework. This integrated approach warrants further examination. The results of this trial have helped inform
future research directions, whereby the team will be evaluating a stepped care approach to treating co-occurring
mental health and drug and alcohol conditions, so that treatment is stepped up according to response.
Expected future outcomes:
CONCLUSION: - There was a strong retention rate over the 10 treatment sessions with a typically challenging
sample, with evidence of overall improvement over time for alcohol consumption, poly-drug use and an aggregate
hazardous day's use score. There was evidence of improvement by group for cannabis, amphetamine, depression
and global functioning.
Name of contact:
Email of contact:
Dr Amanda Baker
(02) 49246605
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
141708
A/Pr Amanda L Baker
Psychiatry
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$387,625.56
Standard Project Grant
Title of research award: Intervention for tobacco dependence among people with a psychotic illness
Lay Description (from application):
The prevalence of smoking among people with a psychiatric illness, especially schizophrenia, is greater than that
in the general population. Exposure to tobacco smoke has been identified as a cause of 32 different diseases as
well as a cause of fire injuries. Tobacco smoke is known to contain carcinogens, as well as nicotine and numerous
other poisonous substances. An extensive body of scientific evidence shows that active cigarette smoking
increases the risk of many different cancers. Smoking related diseases rate second in frequency to suicide as the
greatest contributor to early mortality in schizophrenia. Popular opinion holds that people with mental illness are
lacking in motivation to change their behaviour due to the effects of their mental illness. However, a recent survey
of inpatients in a psychiatric hospital in Newcastle, NSW, revealed that over a quarter of smokers were either
preparing to quit or cut down on their smoking or already had taken action to reduce their smoking. The present
research proposal represents the first large randomised controlled trial of an intervention for tobacco dependence
among people with a mental illness. This project will compare the effectiveness of nicotine replacement therapy
combined with counselling with a self-help booklet on smoking. The proposed research follows a small clinical
study of the feasibility of the intervention and a small randomised controlled trial supported by the Australian
Rotary Health Research Fund. The proposed study brings together the expertise of several people across Australia
who have experience in treating people with mental illness and drug dependence, including tobacco dependence.
The results will inform future clinical interventions for smokers with a mental illness.
Research achievements (from final report):
This trial has led to significant advances in the treatment of tobacco use for people with a psychotic illness. It is
important that the treatment offered in this trial be transferred into routine clinical practice. The results of this trial
indicating that stage of change and number of previous quit attempts at baseline was predictive of more successful
quit attempts has helped inform future research directions. The team is proposing to evaluate a stepped care
approach to treating tobacco use, so that treatment is stepped up according to response.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
209828
Prof Patricia T Michie
Psychiatry
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2002
2005
$246,973.00
Standard Project Grant
Title of research award: Abnormal auditory system function in schizophrenia: an ERP and MEG study of its
origin, course and generality.
Lay Description (from application):
In 1991, an Australian group found that schizophrenia patients have a reduced brain response to deviant sounds in
a repeating pattern of identical sounds. Deviant sounds produce a brain electrical response known as mismatch
negativity which is generated by the auditory cortex in the brain's temporal lobes and by adjacent areas in the
frontal lobes. A smaller mismatch negativity in patients has since been replicated in laboratories in the US, Europe
and Australia. The importance of this finding is that it had not been previously recognised that patients have low
level auditory problems that could potentially have a profound impact on higher level functions. Finnish
researchers have gone on to show in healthy individuals that mismatch negativity can reveal important features
about how well the auditory system works, e.g., for the brain to respond to a deviant sound, it must have a
memory of what happened in the past. Mismatch negativity provides a measure of the integrity of these memory
functions. But it also provides an index of how well the auditory system discriminates different aspects of sound,
pitch, loudness, and temporal features, such as duration. There are hints in our data and from US researchers that
processing of the temporal features of sounds is particularly impaired in schizophrenia. We have also recently
discovered that first-degree relatives of patients may have a similar deficit. The aim of this project is to use
mismatch negativity to probe what is wrong with the auditory system in schizophrenia and those at risk (first
degree relatives). Is it the areas of the brain primarily involved in sound perception (the temporal lobes) that are
faulty or is the problem in the frontal lobes? Is it the case that processing of temporal features are particularly
compromised and if so, is this a biological marker for schizophrenia. Answers to these questions will greatly
enhance our understanding of the nature of the brain dysfunction in schizophrenia.
Research achievements (from final report):
This study featured an exploration of early auditory information processing deficits in schizophrenia. We used an
index of brain function known as mismatch negativity (MMN) which is a response that occurs when the brain
detects a sound that violates a regular pattern or sequence of sounds. It is well known that the size of the MMN
response is significantly reduced in individuals with schizophrenia. In this study we measured the MMN elicited
to sounds that violated a regular pattern by being different in frequency, duration or intensity. Our data indicate
that early in the course of schizophrenia (average duration of illness for early group was 2.6 years) there was a
marked reduction in the MMN response to both duration and intensity deviant sounds. In contrast, the reduction in
MMN to frequency deviant sounds was only apparent in participants with a longer duration of illness (average
duration of illness for this group was 18.9 years). The results suggest that the MMN elicited by a change in sound
duration and/or intensity may be more sensitive to early signs of the illness whilst changes in sound frequency
appear to index progression in underlying brain abnormalities. These results compliment recent findings in other
studies of MMN to frequency and duration changes but is the first study to highlight the potential usefulness of
MMN to intensity changes. The MMN elicited to duration and intensity changes also showed a prominent agerelated decline in the healthy comparison group drawing attention to the importance of considering the impact of
healthy aging when employing these measures.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
Patricia T. Michie
Pat.Michie@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
252480
A/Pr Ulrich A Schall
Mental Health
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$357,500.00
Standard Project Grant
Title of research award: Functional and structural imaging of auditory information processing deficits in recentonset and chronic schizophrenia
Lay Description (from application):
Abnormalities in the auditory system have long been suspected to be present among people who suffer from
schizophrenia and other psychotic disorders, due in part to the high prevalence of auditory hallucinations amongst
these patients. Over the last decade, a group of Australian researchers have identified an index of auditory
information processing, recorded from scalp electrodes, that is abnormal in patients with schizophrenia, and their
biological relatives. The present project will examine the relationship between these electrophysiological findings,
and a new non-invasive technique of functional brain imaging, looking at changes in blood flow, that can identify
the specific brain regions that are active during auditory information processing, and link these to the sources of
the scalp recorded measures. Both of these functional measures will be examined in relation to the volumes of
brain tissue, measured from magnetic resonance imaging scans using new analysis tools, that enable the
identification of subtle changes in brain anatomy. By examining patients who have recently developed
schizophrenia, those who have suffered from the illness for longer periods of time, and their close relatives, this
study will provide the opportunity to identify biological markers of increased vulnerability for the development of
schizophrenia.
Research achievements (from final report):
Abnormalities in the auditory system have long been suspected to be present among people who suffer from
schizophrenia, due in part to the high prevalence of auditory hallucinations amongst these patients. Over the last
decade, a group of Australian researchers have identified an index of auditory information processing, recorded
from scalp EEG electrodes, that is abnormal in patients with schizophrenia. We examined patients who have
recently developed schizophrenia and those who have suffered from the illness for longer periods of time and
close relatives. While our data analysis is still in progress, preliminary data identified the sources of the auditory
information processing deficit bilaterally in the temporal lobes within the auditory cortex using various functional
brain imaging techniques. This deficit is already present at an early stage of the illness while it becomes less
prominent in older cohorts due to normal ageing. Our priliminary analysis also suggest an association of grey
matter reduction with abnormal auditory information processing. This novel finding may help to explain how
subtle regional changes in the brain relate to impaired brain function in schizophrenia.
Expected future outcomes:
Ongoing data analysis aims to link the observed deficits more specifically to other impaired brain functions in
schizophrenia, such as verbal memory, global and executive function, and psychotic symptoms.
Name of contact:
Email of contact:
A/Prof Ulrich Schall
Ulrich.Schall@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
252486
A/Pr Amanda L Baker
Psychiatry
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2003
2007
$0.00
Clinical CDA
Title of research award:
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Receipt of this award has enabled dedicated focus on clinical research activities which have resulted in numerous
grants, publications in leading scientific journals (American Journal of Psychiatry, British Journal of Psychiatry
and Addiction) and dissemination of findings into clinical practice. I have recently taken up a NHMRC Senior
Research Fellowship (2008-2012). Since 2003 I successfully supervised eight theses focusing on comorbidity. I
built a strong research team which fluctuates in size between 10-20 staff, depending on stage of grant funding. A
post-doctoral research fellowship was awarded to my group by the University of Newcastle in 2006 for three
years. This allows a PhD level clinical psychologist to develop our comorbidity research into comorbidity of
depression and cardiovascular disease. Thus, capacity has been built in existing research, comorbidity of mental
health and drug and alcohol problems and a new line of research, comorbidity of depression and physical health
problems. The book "Clinical Handbook of Treatment for Co-existing Mental Health and Drug and Alcohol
Problems" edited by myself and Prof Richard Velleman was published in January 2007 by Routledge.
Expected future outcomes:
I have been awarded a NHMRC Senior Research Fellowship and hope to continue research into the treatment of
comorbidity. I have recently been awarded funding from the University of Newcastle to begin collaborations with
A/Prof Jill Williams, an expert on smoking cessation among people with schizophrenia, a major line of research I
would like to build up.
Name of contact:
Email of contact:
Amanda Baker
Amanda.Baker@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
300734
Prof Vaughan J Carr
Psychiatry
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$365,000.00
Standard Project Grant
Title of research award: A comparative structural and functional cerebral MRI study of first episode
schizophrenia and long-term cannabis use
Lay Description (from application):
Cannabis is used for its subjective effects that include euphoria, depersonalisation, somnolence, and altered
perceptions of temporal contingency.It is a controlled substance yet one quarter of Australian adolescents and
seven percent of adults use cannabis regularly. Chronic use of cannibis can impair frontal brain functioning,
affecting the capacities for attention, working memory and concentration.These neurocognitive deficits bear
striking similarities to those associated with the negative symptom cluster of schizophrenia,which is related to
frontal brain dysfunction. The proposed study will be the first of it's kind to apply sophisticated neuroimaging
techniques to investigate how long-term adolescent cannabis use effects the structure and function of the brain and
to make comparative analyses with the brain changes associated with first episode schizophrenia. We predict that
structural brain abnormalities that are consistent in localisation, if not in degree, will be detected in long-term
cannabis using and first episode schizophreniaparticipants and that there will be even more profound
abnormalities in the first episode schizophrenia cannabis users. We will use the Tower of London (TOL) task to
activate certain areas associated with executive functioning (for instance attention, memory, and strategic
planning). Here, we expect lower intensity activation of the prefrontal cortex during TOL performance both in the
cannabis and first episode schizophrenia groups and that the activation will be lowest of all for the cannabis using
first episode schizophrenia group. The methodology to be applied in this study offers a unique opportunity to
enhance our understanding of the structural and functional markers of first episode schizophrenia and cannabis use
in the neural substrate.
Research achievements (from final report):
This study has made progress in elucidating the brain changes associated with long-term cannabis use and
schizophrenia, and how these changes are related to frontal-parietal-temporal neural network dysfunction. The
results of this study have important implications for understanding the pathophysiology of schizophrenia, the
potential role of cannabis in precipitating a first episode of schizophrenia and the poorer prognosis associated with
cannabis use in schizophrenia.
Expected future outcomes:
As the data analyses are ongoing, we expect that several papers will follow from this project.
Name of contact:
Email of contact:
Martin Cohen
Martin.Cohen@hnehealth.nsw.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
252932
Dr Christopher V Dayas
Neurosciences not elsewhere classified
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2003
2008
$268,000.00
CJ Martin Fellowship
Title of research award: Neural Links Between Drug Addiction and Stress
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
Provided the first demonstration that hypothalamic neurons, specifically, those expressing cocaine and
amphetamine-regulated transcript within the arcuate nucleus and orexin with the perfornical area and lateral
hypothalamus are recruited by stimuli-linked to ethanol availability. Identified a potential interaction between
these two commonly opposing hypothalamic peptide systems. Has significant implications for the understanding
of addiction relevant behaviours and may also contribute to or understanding of compulsive eating disorders and
perhaps obesity.
Expected future outcomes:
These novel studies provide a basis for future experimental exploration into mechanisms designed to prevent
relapse to drug seeking and to expand our understanding of the mechanisms behind which drug addicts tend to
express behavioral disorders such as depression and anxiety.
Name of contact:
Email of contact:
Christopher Dayas
Christopher.Dayas@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
351129
A/Pr Ulrich A Schall
Mental Health
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$440,000.00
Standard Project Grant
Title of research award: Functional neuroimaging of prepulse inhibition in schizophrenia and Parkinson's
disease
Lay Description (from application):
Inhibition deficits have been consistently demonstrated in a broad spectrum of neuropsychiatric conditions that
have been implicated with altered neurotransmitter function of the brain. These conditions include mental
disorders like schizophrenia, obsessive-compulsive disorder, and pathological gambling and neurological
disorders like Huntington's disease, Gilles-de-la-Tourette syndrome and other conditions which are characterised
by impaired impulse control. Studies on animal models suggest that an impaired dopamine neurotransmission either genetically pre-determined and/or stress-induced by environmental factors - may significantly contribute to
a common pathological mechanism across these conditions that, in turn, results in impaired 'sensory motor gating',
a physiological measure of inhibitory brain processes. Traditionally, sensory motor gating is indirectly measured
using the acoustic startle eye-blink response. However, this peripheral measure cannot directly assess the brain
processes underlying sensory motor gating. This study will apply new functional brain imaging methodology and
EEG-based source localisation techniques to assess the neural substrates of inhibitory processes involved in
sensory motor gating in two neuropsychiatric conditions that involve dysfunctional dopaminergic mechanisms:
schizophrenia and Parkinson's disease.
Research achievements (from final report):
Inhibition deficits have been consistently found in a broad spectrum of mental conditions like schizophrenia,
obsessive-compulsive disorder, pathological gambling and neurological disorders like Huntington's disease, and
Gilles-de-la-Tourette syndrome as well as other conditions, which are characterised by impaired impulse control.
Studies on animal models suggest that impaired dopamine function may significantly contribute to a common
pathological mechanism across these conditions that, in turn, results in impaired sensorimotor gating which
measures inhibitory brain processes. Traditionally, sensorimotor gating is recorded as eye-blink response to loud
noise and its inhibition when presented with a subtle warning signal. However, this measure cannot directly assess
the brain processes involved in sensorimotor gating. Hence the current study has applied novel functional brain
imaging techniques to assess sensorimotor gating in schizophrenia and Parkinson's disease. The resuslts indicate a
primary and a seconday neural circutry of sensorimotor gating. The primary circuitry largely involves brain stem
nuclei that is processing sensorimotor gating of the eye-blink reflex. A secondary cortical cicuitry mediates
attention modulation of sensorimotor gating.
Expected future outcomes:
The identification of these neural circuits will assist early detection of impaired dopamine function and it's
association with emerging clinical symptoms of the respective disorders. It will also allow to assess
pharmacological treatment and assist more targeted intervention, particularly in the early stages of the disorders.
Name of contact:
Email of contact:
Ulrich Schall
Ulrich.Schall@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
351145
Prof Trevor A Day
Central Nervous System
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$583,875.00
Standard Project Grant
Title of research award: The neurobiological basis of individual differences in susceptibility to the consequences
of stress.
Lay Description (from application):
Stress plays a major role in the development and progression of many different mental health disorders. However,
as we all know, the effects of stress on one person can be very different from its effects upon another. This is at
least partly explained by differences in individual coping styles. When faced with a stressful situation without a
ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping
strategies, such as avoidance, and those that tend towards active coping strategies, such as attempting to take
control of the situation. Previous studies have provided findings that suggest that passive coping is more common
amongst sufferers of depression, post-traumatic stress disorder, and chronic pain syndrome than is active coping.
But is this cause, or effect? And what are the intervening brain mechanisms? We attempt to address such
questions in the present project using an animal model in which social conflict has been shown to trigger
depression-like symptoms. In particular we wish to: (i) determine whether the patterns of brain activity triggered
by social conflict are different for active vs. passive copers; (ii) determine whether the depression-like
consequences of social conflict are more severe in passive than in active copers; (iii) determine whether
differences in coping style and vulnerability to social conflict stress are due to the actions of a particular
neurotransmitter, dopamine, in the prefrontal cortex of the brain; (iv) determine whether the actions of
antidepressants might be attributable changes in prefrontal cortex dopamine function which in turn promote active
coping in preference to passive coping. These studies will provide exciting new information about the
neurobiological basis of individual differences in vulnerability to the harmful effects of stress, and thus will offer
the hope of developing new ways of preventing devastating illnesses such as depression.
Research achievements (from final report):
Stress contribute significantly to the development and progression of mental health disorders. One approach to
reducing the occurrence of mental health problems would be to develop treatments that increase stress resilience.
To do this, however, requires that we better understand the basis of stress resilience. Previous studies on humans
suggest that differences in coping styles are an important factor; for example, individuals who adopt 'passive'
coping strategies (e.g. avoidance) are found to be over-represented amongst sufferers of disorders such as
depression, relative to individuals who adopt 'active' coping strategies (e.g. directly engaging with the source of
their problems). Unfortunately, in human studies it can be difficult to determine whether differences in coping
style are the cause or the consequence of differences in stress resilience. Therefore, we established an animal
model designed to allow us to explore, in a very controlled manner, the relationship between coping style, stress
vulnerability, and the underlying brain mechanisms. Our results have shown that differences in coping style do
indeed predict differences in an individual's acute and long-term responses to stressful events, adoption of active
coping strategies being associated with greater stress resilience that is under-pinned by significant differences in
the activation of stress response circuitry in the brain. These studies confirm previous suspicions as to the role of
coping style in modulating stress resilience and provide the basis for further studies that will help us to develop
new ways of preventing stress-related mental health disorders such as depression.
Expected future outcomes:
The outcomes achieved in this project can now be followed up with studies that identify specific neural
mechanisms that control coping style preferences, the aim being to determine treatments that alter their function
so as to confer greater stress resilience and thus reduce vulnerability to mental health disorders.
Name of contact:
Email of contact:
Prof Trevor A Day
trevor.day@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
401241
Prof Brian Kelly
Mental Health
University of Newcastle
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$0.00
Standard Project Grant
Title of research award: Living in a rural community: Determinants and consequences of mental health and
well-being
Lay Description (from application):
Th e proposed study will investigate individual, family and community factors associated with the mental health
and wellbeing of residents in rural communties of NSW. It will also examine rural residents' perceptions of their
mental health needs and their access and utilisation of health services. The study will be conducted in 3 rural Area
Health Services in NSW (Greater Western,Hunter New England and North Coast) comprising 70% of the rural
population of NSW. These health regions encompass rural, remote and coastal NSW. We aim to conduct the mail
and telephone survey on adults residing in 4000 households across the 3 regions. Unique aspects of the study
include: i) Examination of a diverse range of rural communities which will provide the opportunity to investigate
the influence and interaction of specific community characteristics on mental health. These community factors
will include social and economic factors, severity of rural environmental stress (eg drought), and the levels of
access to health and other services. ii) Focus on the household and its members so as to examine the mental health
needs of family groups in rural communities. This cross-sectional study will form the baseline for a longitudinal
study investigating the changes experienced by rural families over time and the impact of such change on mental
health outcomes.
Research achievements (from final report):
The Australian Rural Mental Health Study (ARMHS) is a large multisite mental health study of residents in rural ,
remote and coastal regions of NSW and was designed to form the baseline for longitudinal research investigating
individual, household and community influences on mental health and related disability over time. ARMHS has
recruited a cohort of 2,613 individuals (1,854 households) with parent reports of child health for 559 children.
Participants have consented to follow up and many have already completed the 12 month follow up phase
(separately funded by CRRMH and Australian Rural Health Research Collaboration. The study has consulted with
the 2007 Australian National Survey of Mental Health and Wellbeing project to enable commplementary methods
(specifically use of components of the ANSMHWB-2 version of CIDI). Results from ARMHS will inform health
policy and service development to meet current and changing needs of rural and remote communities. An
important and unique aspect of the ARMHS research has been an investigation of social, community and
geographic influences on health outcomes in rural areas. The data set will provide information regarding service
access for mental health problems in rural and remote regions; patterns of comorbidity of physical and mental
illness; and the impact of environmental adversity such as drought. ARMHS has led to increased rural research
capacity through collaboration with a diverse range of organisations; support for research students working on
ARMHS and the unique linkage with rural mental health services.
Expected future outcomes:
Provision of new information regarding patterns of mental health problems, their determinants and outcomes
across diverse regional, rural and remote communities, including the role of individual, household and community
level factors.
Name of contact:
Email of contact:
Professor Brian Kelly
Brian.Kelly@newcastle.edu.au
NHMRC Research Achievements - SUMMARY
University of Queensland
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
102431
Prof Susan H SPENCE
Mental Health
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2001
2002
$304,581.00
Standard Project Grant
Title of research award: Adolescent depression: Evaluation of a preventive intervention and identification of risk
factors
Lay Description (from application):
This project will evaluate the long-term effectiveness of a school-based program to prevent depression among
adolescents. It also aims to identify factors that predict the onset of depression in those who do not receive the
intervention. The intervention focuses on the training of interpersonal problem solving skills and enhancement of
optimistic thinking styles within a classroom-based curriculum. This project extends the current research program
of the applicant. The intervention has already been developed and implemented with 1600 young people, with the
support of local education authorities. The evaluation uses well-researched measures and includes a control group
of adolescents who do not receive the intervention. Around 5% of adolescents experience clinical levels of
depression and an even larger percentage show subclinical levels. Depression results in many debilitating
consequences such as impaired school, work and social functioning and is also a risk factor in adolescent suicide.
The prevention of mental health problems is a priority for Commonwealth and State governments and yet there is
minimal research to demonstrate the effectiveness of preventive interventions, particularly in the area of
depression. If the present study demonstrates a positive outcome, it will provide important guidelines as to
preventive materials that should be included in the school curriculum. It is predicted that: a) the intervention will
be associated with lower levels of depression over the 4 year follow-up, particularly for adolescents who are
assessed as showing mild symptoms of depression, poor problem solving skills or pessimistic cognitive style prior
to intervention b) risk factors for the development of depression in adolescents who do not receive the intervention
will include initial mild symptoms of depression, poor problem solving skills and pessimistic attributional style.
Research achievements (from final report):
This project evaluated the long-term effectiveness of a school-based universal program designed to prevent the
development of depression in adolescents. A total of 1500 Year 8 students from 16 high schools participated in the
project. A total of 751 students received a cognitive behavioural intervention designed to enhance life problemsolving skills, problem-solving orientation and adaptive explanatory style delivered by teachers in the classroom.
The remaining 749 students participated as a monitoring-only comparison group. The intervention was found to
produce significant short-term benefits in terms of greater improvements in problem solving skills and reductions
in depressive symptoms in the intervention group in comparison to the monitoring-only group. However, at
follow-up assessments three and four years later these benefits were no longer maintained for students either with
low symptoms of depression or with high symptoms of depression in the intervention group. This project
emphasises the importance of long-term follow-ups in evaluations of programs designed to prevent the
development of depression and raises further questions about the benefits of brief, school-based universal
approaches to prevent depression in young people. The research also sought to identify factors predicting the onset
of depression in adolescence. Analyses of the data found that depressive symptoms at 1-year follow-up,
controlling for baseline depression levels, were predicted by negative life events in the previous 12 months,
attributional style, negative problem solving orientation, and the interaction between negative life events and
negative problem-solving orientation. In the presence, but not absence of higher levels of negative life events,
negative problem-solving orientation predicted increases in depressive symptoms. However, pessimistic
attributional style predicted future increases in depression irrespective of the occurrence of negative life events.
Expected future outcomes:
This research will provide further information about the long-term predictors in the development of adolescent
depression and will inform government policy relating to prevention of depression in young people.
Name of contact:
Professor Susan H Spence
Email of contact:
s.spence@psy.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
142990
Dr Kathryn M Buller
Central Nervous System
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$411,724.12
Standard Project Grant
Title of research award: Central control of stress-induced changes in immune function
Lay Description (from application):
LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is
often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially
disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain
can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone
called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the
infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the
adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually
hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection
is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of
the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence
those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or
irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain
operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our
immune systems.
Research achievements (from final report):
The common assumption that stress is harmful has received increasing amounts of scientific support in recent
years especially in regard to the effects of psychological stress on susceptibility to infectious disease. We are in an
excellent position to further our investigations into determining which brain pathways contribute to how
psychological stress affects one’s susceptibility to disease. We wish to follow up our findings by investigating
how stress can modify the effects of other proinflammatory mediators in the brain. Also, many effects in the body
are being attributed to the sympathetic nervous system and we plan to examine the stress and cytokine pathways
responsible for changes known to occur in immune organs during times of stress. A clear understanding of how
exposure to stress modifies the operation of mechanisms that regulate immune function is essential if we are to
develop appropriate preventative treatments for individuals exposure to stress and infection.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
143021
Prof Justin A Kenardy
Mental Health
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$185,000.00
Standard Project Grant
Title of research award: A prospective study of traumatic stress in children involved in motor vehicle accidents
Lay Description (from application):
Motor vehicle accidents (MVAs) are relatively frequent major life trauma that represent significant life
threatening experiences. Not surprisingly evidence suggests that MVAs represent a frequent trigger for the
development of post traumatic stress disorder (PTSD), although studies have typically focussed upon adult
survivors. Local statistics indicate a significant proportion of children will experience a MVA of sufficient
severity to warrant attendance at hospital. This project is of significance because it will provide badly needed
information about the prevalence and course of emotional and behavioural problems in children following
exposure to a serious MVA. More broadly the study should provide valuable information on post-traumatic stress
responses in children. Furthermore, it will enable us to identify the factors that place children at particular risk of
developing psychological problems following a MVA. This will provide information to help design of
interventions to prevent the development of PTSD and other forms of psychopathology following MVAs. Such
data will also permit identification of those children who are at particular risk of psychological morbidity after
MVA trauma and for whom preventive interventions are most likely to be beneficial.
Research achievements (from final report):
This project investigated the prevalence of post traumatic stress reactions in children injured in accidents, with
follow-up of families occurring within two weeks after the child's accident, at one month after the accident and
again at six months after the child's accident. Children were aged 7 to 15 at the time of the accident. The research
employed measures of child functioning as well as parental functioning. The study found that although a
significant number of children suffered initial distress at two weeks after the accident, the majority of children
made a relatively good psychological recovery. However, children who suffered significant distress at one month
after the accident were likely to still suffer from post traumatic symptomatology at six months after the accident.
This indicates that early identification of children suffering significant psychological distress allows for early
treatment of children who are unlikely to recover without intervention.
Expected future outcomes:
The outcomes of this research will form the basis of development of an intervention program aiming to prevent
and/ or minimise development of post traumatic stress disorder and other psychological disorders in children
injured in accidents. The risk factors identified in the original study allow early identification of children at risk
for development of these disorders.
Name of contact:
Email of contact:
A/Prof. Justin Kenardy
jkenardy@somc.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
224246
Prof Pankaj Sah
#N/A
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2003
2003
$450,000.00
Standard Project Grant
Title of research award: Excitatroy synaptic circuitry and plasticity in the amygdala
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
We have discovered some novel mechanisms in excitatory synaptic tranmission in the lateral amygdala. These
results will greatly improve our understanding of how emotion related information is processed. .
Expected future outcomes:
In the future this work may lead to the development of novel therapies aimed at treating anxiety related disorders.
Name of contact:
Email of contact:
Pankaj Sah
pankaj.sah@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
143027
A/Pr Bryan J Mowry
Psychiatry
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2001
2004
$265,000.00
Standard Project Grant
Title of research award: A Genetic Study of Schizophrenia in the Brahmin of Tamil Nadu
Lay Description (from application):
The cause of schizophrenia is unknown, but there is good evidence that genes play a role. Geneticists do not fully
understand how it is inherited, but it is very complex, and several interacting genes as well as environmental
factors are probably involved. Societies such as Australia are genetically diverse because people from many
different ethnic groups have intermarried. To detect susceptibility genes in this type of population, we must study
very large patient samples. Alternatively, we can study genetically homogenous patient samples, found in
"isolated" gene-pool populations. One such population is the Brahmin people in Tamil Nadu, a south-eastern state
of India. The Brahmin are descended from the Aryan peoples who migrated into southern India 2000 years ago. In
the Hindu caste system, Brahmin are the highly educated priest class, and enjoy a privileged position in society.
Traditionally, marriages among the Brahmin of Tamil Nadu have been prearranged, with a preference for firstcousin marriages. As well as this cultural and historical evidence, genetic marker studies confirm that this
population is a suitable genetic isolate. In this project, genetic material (DNA) will be collected from Brahmin
schizophrenic patients and their families. Diagnostic data, detailed family data, and blood samples will be
gathered from 90-100 extended families, each containing two or more ill individuals. Analysis of their genetic
code will enable a search for possible schizophrenia susceptibility genes and a systematic search for a mutation. If
found, this will greatly improve our understanding of schizophrenia, and stimulate the search for similar genes in
other samples world-wide, including Australia where schizophrenia costs $3 billion annually in terms of treatment
and lost jobs. If schizophrenia genes can be found, it may be possible to find better treatments that correct the
basic causes of the illness and identify factors that protect against the illness.
Research achievements (from final report):
The aim of this project was to recruit (1) 90-100 pedigrees with two or more cases of schizophrenia from within
the Brahmin of Tamil Nadu, a restricted gene-pool population in southern India; (2) a sample of at least 100 trios
(probands and both parents) to aid in fine-mapping studies. The stated objectives were surpassed. One hundred
and six Affected Sibling Pair (ASP) families and 121 complete trios were recruited. All available medical records
were also obtained for affected individuals. Two hundred and twenty five family history interviews and 358
structured diagnostic interviews have been conducted. Nine hundred and thirty blood samples (730 from affected
families and 200 from controls) were taken and DNA was extracted for future genetic analyses. A relational
database has been developed for comprehensive data entry. This includes family (family history, pedigree
drawing) and individual details (interview, a number of dimensional rating scales). All families were entered into
Progeny, a pedigree drawing and management database. These data have provided the first component of a
growing cohort of an estimated 400 pedigrees and 400 trio families. Analysis of the genetic code of these
individuals has commenced.
Expected future outcomes:
The goal is to identify schizophrenia susceptibility genes. If found, this will greatly improve our understanding of
schizophrenia, and facilitate the development of better treatments that correct the basic causes of the illness.
Name of contact:
Email of contact:
A/Professor Bryan Mowry
bryan_mowry@qcmhr.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
210215
Dr Elizabeth MJ Gillam
Toxicology (incl. Clinical Toxicology)
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$214,036.00
Standard Project Grant
Title of research award: A Novel Physiological Role for Cytochrome P450 Enzymes in the Brain
Lay Description (from application):
The cytochrome P450 enzymes in human liver have been traditionally regarded as drug metabolising enzymes.
However, it is now becoming clear that they are distributed in other tissues in the body and that they may serve
important and diverse roles in normal physiology. Little is known about their functions in the brain. We have
identified a reaction catalysed by these enzymes that generates a chemical found in the brain normally, whose
levels are elevated under stress and which, when given to animals, is anxiogenic. This points to a possible
involvement of P450 enzymes in a hitherto unexplored branch of the stress response. Importantly, it may lead to
the development of novel drugs that block the P450 and therefore block production of the anxiogenic chemical.
This proposal is designed to explore the basic biology underlying this system.
Research achievements (from final report):
The cytochrome P450 enzymes have been traditionally regarded as drug metabolising enzymes. We identified a
reaction catalysed by these enzymes in the brain that generates a chemical found in the brain normally, whose
levels are elevated under stress and which, when given to animals, is anxiogenic. This points to a possible
involvement of P450 enzymes in a hitherto unexplored branch of the stress response and anxiety. We were able to
identify which P450s may be responsible for this reaction, and define where they were distributed within the
brain. This will facilitate further studies to show whether this reaction can be blocked by novel drugs to cause a
therapeutic anxiolytic effect.
Expected future outcomes:
This study will lead to a better understanding of the roles of cytochrome P450 enzymes in brain biochemistry and
in the clearance of chemicals from the brain. In the longer term, this project should lead to the development of
novel drugs to treat anxiety disorders.
Name of contact:
Email of contact:
Dr. Elizabeth M.J. Gillam
e.gillam@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
210250
Dr Guy N Elston
Central Nervous System
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$362,820.00
New Investigator
Title of research award: Anatomical substrates of primate executive control
Lay Description (from application):
When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in
different regions involved in various processes. While, at a first approximation, this may be a reasonable approach
to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure.
In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human
brain. The study of cortical circuitry that underlies the diversity in cortical processing reached a zenith and there
was a renaissance in understanding of brain function. These researchers were, however, limited by techniques
available to them at the time. With the advent of new methodologies which allowed scientists to explore
individual connections between cells (synapses), to probe structure and transmission across synapses, and to
record from live neurones, new and exciting discoveries were made. However, these methodologies are highly
time consuming and studies became necessarily more focussed. As a result, there was a tendency in the later half
of the 20th century to extrapolate findings from one cortical area to cortex in general. Even more precarious,
anatomical and functional findings in highly specialized sensory cortex of one species were projected to other
distantly related species. Such thinking lead to a "dark age" in neuroscience. It became widely accepted that there
exists a "canonical" circuit. Consequently, differences in function between different cortical areas were attributed
solely to the source of their projections. The central thesis of this project is to study aspects of cell structure and
cortical circuitry in the prefrontal lobe. We hope that the project will provide another step in the pathway that
leads to understanding the mind.
Research achievements (from final report):
The PI has made a significant contribution to the understanding of the microstructure of the cerebral cortex, be it
visual, somatosensory, motor, cingulate or prefrontal. He has published a book, six book chapters and 22 peer
reviewed journal articles related to the objectives outlined in his original proposal over the space of three years. In
addition to contributing to the understanding of cortical organization, he has spearheaded new research into
cortical abnormalities in Down syndrome and is studying the effects on cortical structure of commonly prescribed
antipsychotics used in the treatment of schizophrenia. He has set up labs in 4 countries to be able to do this, has
attracted significant international funding, has been inveited to chair special sessions at international conferences
and has been awarded several international prizes.
Expected future outcomes:
A better understanding of regional specialization in cortical circuitry, both structural and functional, which will be
important when developing stem cell therapies and the treatment of mental illness
Name of contact:
Email of contact:
Dr Guy Elston
G.Elston@vthrc.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
210297
Start Year:
Prof Jake M Najman
End Year:
Medical and Health Sciences not elsewhere classified
University of Queensland
Grant Type:
2002
2004
Total funding: $420,700.00
Standard Project Grant
Title of research award: Mother's history of mental health impairment and its impact during mid-life
Lay Description (from application):
There have been few specific studies of the health of women in mid-life. In mid-life, mental health impairment
and health problems associated with biological and social transitions (e.g. menopause) are major concerns.
National estimates indicate that between 15% and 20% of women in the mid-life age range have experienced a
mental illness in the past year. The proportion of women experiencing a combination of emotional and physical
symptoms, frequently associated with the menopause, is likely to be somewhat higher. This proposal involves
merging information collected initially from 1981 onwards, with data on the mother's mental and physical health,
to be collected in this follow-up. Women in this study (8556) were enrolled at their first obstetrical visit and they
have been followed up shortly after the birth, when the child was 6 months, 5 years and 14 years. On each
occasion extensive information has been obtained on the mother's mental and physical health, as well as on the
child's health and development. This study will examine the chronicity of the mother's mental health symptoms
over a 21-year period, and assess the association between her early mental health, the child's health and her current
health status. This is the only large Australian cohort study to have followed a sample of women for 21 years. It
will permit us to understand more of how women's health changes over time and the factors associated with these
changes. It will provide the first large-scale study of factors influencing women's health transition through the
menopause.
Research achievements (from final report):
This project represents the continuation of research that commenced between 1981 and 1983, when over 8,000
mothers-to-be were approached to join the Mater-University Study of Pregnancy and its Outcomes as they
attended their first antenatal visit at the Mater Mothers Hospital in Brisbane, Queensland. Subsequently, over
7,000 of these women delivered live babies at the study hospital and the health of these mothers and children have
been monitored at various stages up to 21 years after the birth of the child. The current study represents the 21year follow-up of the study mothers. Around 4,051 participated in this phase of the study, providing researchers
with a mass of data related to physical and mental health, health-related behaviours, sociodemographics,
menopausal status and symptoms, quality of life, as well as social circumstances and experiences. Few studies in
the world have tracked the health and wellbeing of a large sample of women from before the birth of a child until
21 years post-delivery. The Mater-University Study of Pregnancy therefore provides a unique opportunity to
investigate mental and physical health outcomes in mid-life while considering prior mental health and physical
wellbeing, health-related behaviours, family circumstances, socioeconomic status, size of family, and quality of
neighbourhoods, and changes/continuity in/of these influences across time.
Expected future outcomes:
Through the data collected during the 21-year follow-up, the mental and physical health and wellbeing of mothers
will be tracked and examined over a period of more than two decades, to determine the extent that social
circumstances, family-related factors, prior health and wellbeing, and health-related behaviours, contribute to
healthy ageing.
Name of contact:
Email of contact:
Professor Jackob M. Najman
j.najman@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
210298
Start Year:
Prof Jake M Najman
End Year:
Public Health and Health Services not elsewhere classified
University of Queensland
Grant Type:
2002
2004
Total funding: $694,000.00
Standard Project Grant
Title of research award: Pathways to mental health and obesity in young adults: A longitudinal study
Lay Description (from application):
While the health of the population has been gradually improving, there are some health problems which are
increasing. The mental health of young people is one such area. Based on data relating to youth suicide, substance
abuse, cigarette smoking by females and behavioural or mental health problems in the young, there has been
evidence of a marked increase in some important health problems faced by the young. Little is known about the
causes of these problems and even less is known about the reasons for the increase. Based on the available
evidence, 20-25% of young persons manifest a mental health problem. A second area of marked health
deterioration concerns youth (and adult) obesity. Existing research points to the accumulation of cardiovascular
risk factors associated with obesity from a very early age. Over 10% of youth are obese and a substantially higher
proportion are overweight. There is evidence that the rate of obesity has been substantially increasing. Again little
is known about the factors that contribute to obesity or the causes of the increase in the rates of obesity in the
population. This proposal is for a 21-year follow-up of a sample of youth first enrolled when their mothers
attended for their first obstetrical visit. Using a substantial body of existing data, we propose to examine the
changes in levels of mental health and obesity and to identify the factors which contribute to these changes. This
study involves the largest Australian cohort ever assembled for such research. The main questions asked in this
study concern the impact of the mother's social and economic circumstances, her physical health and well-being,
her use of addictive substances (including alcohol, cigarettes, illicit drugs) on the youth's health. We will also
examine the association between early indicators of mental health and well-being and subsequent youth health and
development.
Research achievements (from final report):
This project represents the continuation of research that commenced between 1981 and 1983, when more than
8000 mothers-to-be were approached to join the Mater-University Study of Pregnancy and its Outcomes as they
attended their first antenatal visit at Mater Mothers Hospital. Subsequently, over 7,000 of these women delivered
live babies at the study hospital and the health and well-being of these mothers and children have been monitored
at various stages up to 21 years after the birth of the child. The current phase of the study represents the 21-year
follow-up of the study children. Just under 4,000 of these now young adults participated in the 21-year follow-up,
providing researchers with a mass of data related to physical and mental health, physical growth, health-related
behaviours, sociodemographics, driving behaviour, as well as social circumstances and experiences. This data is
being combined with that gathered at previous phases of the study enabling the examination of a wide range of
influences operating during the developing years for their connections to health outcomes in young adulthood.
Few studies in the world have tracked the growth, development and well-being of individuals from the prenatal
period, through to childhood, adolescence, on to adulthood. The Mater-University Study of Pregnancy therefore
provides a unique opportunity to investigate the extent that child development and well-being, family
characteristics, and environmental factors across the child's developing years contribute to physical and mental
health outcomes as the child reaches adulthood.
Expected future outcomes:
The Mater-University Study of Pregnancy, through examination of data collected from the prenatal period to 21
years post-delivery, will be able to examine relationships between family-related factors, social and behavioural
influences occurring during the fetal period, infancy, childhood and adolescence, and the development of obesity
and mental illness among young Australian adults.
Name of contact:
Email of contact:
Jackob M. Najman
j.najman@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
219117
Prof Stanley V Catts
Psychiatry
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
Program
2002
2004
$400,000.00
Mental Health Early Psychosis
Title of research award: Evaluating the relationship between clinical practice guideline implementation and
client outcomes in early psychosis programs
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
This project designed and implemented a clinical practice improvement network for early psychosis. A national
census of early psychosis initiatives was performed. Nine area mental health services were recruited to a
prospective evaluation of the first six-months of treatment of early psychosis patients. Patient and carer feedback
was surveyed. For the first time across-service aggregation of patikent-level data was possible using procedures
and tools designed to measure clinical practice coded for clinical guideline adherence and health outcomes that
were approved by ethics committees as quality assurance and for use in the routine monitoring of mental health
service effectiveness. Multilevel modelling enabled partitioned effects on patient and carer outcomes of clinical
intervention and service program characteristics to be determined. If the procedures and tools designed by the
project were refined and automated, and routinely implemented in mental health services by supporting clinical
practice improvement (see full report).
Expected future outcomes:
Ten to 20 publications; contribute to the updating of the clinical guidelines for early psychosis; provide best
practice models for the development of lical mental health service information management systems and routine
effectiveness measurement as quality assurance; and, facilitate the evaluation of best practive modes for mental
health service delivery to indigenous and rural communities.
Name of contact:
Email of contact:
SV Catts
s.catts@mailbox.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
143250
Prof Ross McD Young
Endocrinology
University of Queensland
Start Year:
2001
End Year:
2005
Total funding: $140,373.00
Grant Type: NIDS Project - National Illicit
Drugs Strategy 26
Title of research award: A pharmacogenetic approach to the treatment of opiate dependence using the D2
dopamine receptor gene.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
In contemporary Australia heroin misuse poses a significant health, social and ecomomic burden. This open label
study examined the benefit of the antidepressant citalopram as an adjunct treatment to methadone treatment in a
group of heroin dependent individuals.The study recruited 169 potential participants. Of this pool of potential
participants most were ineligable for the study. The single most common reason for ineligability was that
participants were currently prescribed Buprenorphine instead of methadone to treat their heroin dependence (a
total of 47 excluded participants). The second most common reason was that potential participants were currently
taking an antidepressant and thus could not be commenced on another antidepressant at the same time (a total of
31 excluded participants). Twenty participants commenced the trial and all were tested to establish which form of
a gene associated with substance misuse was present. This gene, the D2 dopamine receptor gene, has two forms
(or alleles) and we hypothesised that those individuals who had either one or two alleles of the A1 form would
have better outcomes. This is because citalopram can increase the number of D2 dopmaine receptors in the brain.
A lessened number of these D2 receptors has been found in those with the A1 form of the gene when compared to
their A2 counterparts. Excactly 50% of those recruited had each form of the gene. Our analyses are not yet fully
complete but it those who left the trial early due to the medication not being tolerated had the A2 version of the
gene. For those who remained in the study their mental health improved, their heroin use decreased, as did their
cannabis use. These improvements appear to be most marked in those with the A1 version of th DRD2 gene
indicating that this group is an important target group for this treatment. However, all of those who stayed on the
trial chose to remain taking the citalopram at the end of their follow-up.
Expected future outcomes:
Our future plan is a personalised matching of medications and other treatments to individuals with substance
misuse problems based upon genetic risk. The future will also see the development of genetic tests that will be
able to provide rapid feedback of these risks so that treatment selection can be made promptly and with less risk of
adverse effects.
Name of contact:
Email of contact:
Professor Ross Young
rm.young@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
252777
A/Pr Bryan J Mowry
Mental Health
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2003
2005
$457,500.00
Standard Project Grant
Title of research award: Structural and diffusion tensor neuroimaging in twins concordant and discordant for
psychosis
Lay Description (from application):
Measures from specialised brain scans i.e. MRI's (Magnetic Resonance Imaging) have suggested that several areas
in the brain are different in those individuals who suffer from psychosis compared to those who don't. Evaluations
of these brain differences have helped us better understand the nature of these illnesses. For example, frontal lobe
dysfunction has been linked with the loss of ability to plan and organize information, seen in those who have
schizophrenia. These measures may also help clarify the relationship between the genetic and environmental
factors contributing to the development of these disorders. One of the best ways to investigate this relationship is
the use of a twin study design. The Australian study of twins with psychosis will recruit dizygotic (DZ) and
monozygotic (MZ) twin pairs in which at least one twin is affected by a psychotic disorder, plus control twin pairs
matched for age, sex and zygosity. Measures derived from MRI scans will be collected in an attempt to further
define specific brain regions reported to be different in psychosis. In addition Diffusion Tensor Imaging (DTI)
will be used to visualize white matter tracts in the brain. The twin study design will allow us to differentiate
genetic and environmental factors associated with these brain measures and help evaluate the potential for these
measures to genetically define sub-groups of individuals with psychotic disorders. The identification of these
subgroups would facilitate the search for susceptibility genes. Additionally, this study will help clarify the
possible clinical overlap between affective (i.e. bipolar affective disorder) and non-affective (i.e. schizophrenia)
psychotic disorders. The information obtained from this study has the potential to greatly improve our
understanding of caustive factors in psychosis, which may also lead to earlier diagnosis and treatment, thereby
improving prognosis.
Research achievements (from final report):
Measures derived from Magnetic Resonance Imaging (MRI) scans have suggested that several areas of the brain
are different in those individuals who suffer from psychosis compared to those who do not. Monozygotic and
dizygotic twin pairs in which at least one twin was affected by psychosis, plus matched control twin pairs with no
history of psychosis, were recruited. Analysis of the MRI scans will help to identify specific brain regions which
are different in psychosis. It will also help clarify the relationship between the genetic and environmental factors
contributing to the development of these disorders and facilitate the search for susceptibility genes. The
information from this study has the potential to greatly improve our understanding of causative factors in
psychosis, which may lead to earlier diagnosis and treatment, thereby improving prognosis.
Expected future outcomes:
This research will contribute to further clarification of the nature of psychotic illness.
Name of contact:
Bryan Mowry
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
252904
Prof John D Pettigrew
Central Nervous System
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2002
2005
$140,000.00
Development Grant
Title of research award: Development of a Diagnostic Test for Bipolar Disorder
Lay Description (from application):
A unique test that monitors the rate of switching between the hemispheres of the brain in response to visual
stimuli has been devised. A patent application covers an apparatus and test to measure the switching rate between
the hemispheres and the way in which such measurements can be used as a means to diagnose bipolar disorder
(BD). BD, also called manic depression, is a form of depression that currently affects over six million people
worldwide with about three million in the USA alone. The condition has phases of mania and depression and
periods of remittance. Full cycles of BD can occur as many as three times a year and for many patients, this is a
lifelong condition. BD is effectively treated, once it is diagnosed. It is estimated that 20% of sufferers go
undiagnosed and many more are misdiagnosed. The cost of mis- or non-diagnosis is measured by suicides, the
financial burden on society with health care, loss of productivity etc, effects on family and associates, crime, etc.
Diagnosis to date is achieved mainly by subjective means such as questionnaires. These instruments do not
conclusively separate BD from other forms of depression and schizophrenia, for which treatment is quite different.
Nor do they allow for factors such as substance abuse and other medical conditions that the patient may be
suffering. BD is hereditary with the slow hemispheric switch rate being an indicator of the genetic trait. This
phenomenon allows for an objective test for BD, even if an individual has not had an episode of BD. The slow
switch allows relatively easy separation of a BD patient from those exhibiting symptoms that may have other
causes.
Research achievements (from final report):
A simple, inexpensive and objective test has been developed for bipolar disorder. While a multi-centre trial is
necessary to establish this test in the eyes of the clinical community, it has the potential to make bipolar disorder
preventable with enormous attendant savings in mortality, morbidity and economic losses.
Expected future outcomes:
A multi-centre trial is needed to convince clinicians of the validity and robustness of the test in a variety of
environments. Following such a trial we expect widespread acceptance and marketing of the test.
Name of contact:
Email of contact:
Jd Pettigrew
j.pettigrew@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
301103
Prof Justin A Kenardy
Health, Clinical and Counselling Psychology
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$473,500.00
Standard Project Grant
Title of research award: Project Grant Cognitive impairments and post traumatic stress symptoms in children
with traumatic brain injury: A longitudinal study
Lay Description (from application):
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria
alone. Many children who experience a brain injury go on to have long-term difficulties such as significant
educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury.
However it is not clear to what extent this is so for children who have received a traumatic brain injury.
Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these interact, how
they influence long-term outcomes, and what factors such as pre-injury functioning and family support and
distress mediate outcomes. These issues are very important since effective rehabilitation of children following
traumatic brain injury is essential to maximise long-term functioning and minimise disability. To be effective,
rehabilitation must be guided by the knowledge about key factors that determine the recovery process. This study
aims to provide answers to these questions by following two cohorts of children (aged 6-14) over 18 months after
receiving a traumatic brain injury. In total 240 children will be recruited from Brisbane and Melbourne hospitals.
They will be assessed at three, six, twelve and eighteen months post-injury using measures of cognitive,
psychological and social functioning. Information on parent distress and behaviours will also be obtained. The
information obtained will provide the basis for the development of a specific rehabilitation strategy for children
with traumatic brain injury, including information on strategies to help prevent any confounding impact of posttraumatic stress on recovery.
Research achievements (from final report):
The primary aim of this research was to investigate the psychological and cognitive sequelae of traumatic brain
injury (TBI) in children to examine the relationship between cognitive impairment and post-traumatic stress,
adjustment to injury, and the long-term impact on recovery. This study aims to describe the changing relationships
among key factors predicting outcome from childhood TBI (injury factors, pre-morbid child characteristics, and
family factors) up to 18 months post-injury. The recruitment of children with TBI was completed at the end of
2006. During 2007 the first four assessment time points (pre-injury, three, six, and twelve months) were
completed and we are in the final stages of completing the eighteen month assessments. This study is the largest
head injury study with children in the world examining both cognitive and emotional outcomes. To date, five
papers have been presented at both national and international conferences. Two of the conference presentations
are being developed into papers for submission to peer-reviewed journals. The results indicate a) children's preinjury behaviour does not appear to influence the severity of children's TBI, b) the psychological responses of
children following TBI are better assessed with clinical interviews (CAPS-CA) in comparison to self report
measures (TSCC), c) among children with TBI executive functioning deficits include speed of information
processing and high-order cognitive flexibility, but no apparent deficits in goal setting or reasoning, and, d)
parental distress is associated with the severity of children's TBI and children's psychological reactions but not
their neuropsychological outcomes.
Expected future outcomes:
Final assessments (18-months) will be completed by end of 2008. The next stage of data analysis is to examine
post traumatic stress symptoms over time, the relationship between PTSD and cognitive and behavioural
outcomes, and PTSD and TBI severity, and to explore theoretical issues such as the diagnosis of PTSD in children
with TBI.
Name of contact:
Email of contact:
Professor Justin Kenardy
j.kenardy@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
219327
Prof David Kavanagh
Psychiatry
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
Mental Health
2003
2008
$0.00
Health Research Partnership in
Title of research award: Health Research Partnership in Mental Health - AIMhi (Australian Integrated Mental
Health Initiative)
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The project had 3 streams. The first stream focused on improved indigenous programs in the Top End of Northern
Territory and in remote communities in Far North Queensland; the second stream trained mental health staff in
urban and regional settings in NSW, Victoria and South-East Queensland to apply a recovery orientation to people
with very high ongoing support needs; and the third stream supported general practitioners and mental health staff
across rural and regional Queensland, in addressing relapse and comorbidity issues of people with both high-and
low-prevalence disorders. Our experience showed that a recovery and empowerment orientation can be applied
with positive outcomes in a wide variety of contexts, from individuals with high levels of complex and chronic or
recurring needs, to whole communities. This supports the notion that approaches to chronic or recurring problems
of individuals and communities should go beyond chronic disease self-management to the promotion of "chronic"
or sustained wellbeing. Consistent with past research, we found that short-term training programs can produce
positive changes in practitioners' knowledge, attitudes and demonstrated skills, but transfer to practice is limited,
without additional follow-up that relates that training to specific individuals or experiences. Turnover of
practitioners means that training and support programs need to be ongoing. This was the first mental health RCT
in a remote Indigenous context. A brief intervention, developed with Aboriginal Mental Health Workers,
significantly improved wellbeing, alcohol dependence and life skills. Training significantly increased confidence
in cross cultural communication, assessment and treatment.
Expected future outcomes:
Tools and resources developed by all of the AIMhi streams are now being utilised by other ongoing research
projects. Presentations have also been made to key government departments and the researchers are hopeful that
many of the key findings will be utilised for policy and practice.
Name of contact:
Email of contact:
David Kavanagh
David.kavanagh@qut.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
301204
Prof Perry F Bartlett
Central Nervous System
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2004
2008
$0.00
New Program Grant
Title of research award: Regulation of neural cell production in the normal and diseased brain
Lay Description (from application):
Members of this team are at the forefront of research into the molecular control of nerve cell production and
function in the developing and adult brain. They were responsible, often through collaboration, for many of the
major discoveries demonstrating that stem cells in the brain of adult animals can generate new nerve cells; this
revolutionised our concept of the brain and opened-up the possibility of therapeutic repair of neural damage
through stimulation of a patient?s own stem cells. Discovering the molecular mechanisms controlling this process
is the goal of the present program. In order to achieve this aim we have formed a team on the basis of considerable
past success, as well as future requirements. The team members have the complementary skills to assess all
aspects of the problem, including crucial functional and clinical expertise. By combining resources we will
position ourselves at the very forefront of the international competition to discover and to evaluate clinically the
molecular mechanisms underlying neural repair and regeneration. This is of enormous significance in determining
how we best treat stroke, injury and other neurodegenerative diseases in the next 10 years, and will lead to the
development of new therapeutics of immense value. The team will use innovative approaches such as cell-sorting
to obtain pure populations of stem cells and their progeny in order to identify new therapeutic targets; these will
then be validated in animal models of neurological disease. Since team members have previously been involved in
progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in
partnership with the biopharmaceutical industry.
Research achievements (from final report):
The central hypothesis explored by our program of research was that the brain's innate ability to remodel itself
through the production of new nerve cells, and the formation of new connections (synapses) between these cells,
is important not only to optimal brain function but also provides the machinery to repair and regenerate damaged
and dysfunctional brains. Over the past five years, we have built substantially on our initial discoveries in areas
central to our understanding how the production of new, functionally integrated neural cells is regulated, from
neural precursor production of new neurons and oligodendrocytes, through neuronal migration and survival, to
synapse formation and functional integration. We have taken our discovery of neural stem cells in the adult brain
further by demonstrating several regulatory mechanisms controlling neuronal and oligodendrocyte production and,
excitingly, have recently identified the true stem cell in the hippocampus. This cell has unique properties and is
activated to produce neurons by synaptic activity. Building on our finding that the p75 neurotrophin receptor
mediates neuronal cell death, we have discovered that a novel molecular mechanism mediates this process,
solving the problem of how synaptic activity and growth factors interact to modulate neuronal survival and
providing the potential to prolong the survival of newly generated neurons in the adult brain. Building on our
discoveries of interneuron migration, we have also determined several of the key molecular regulators of this
process, giving us insight into how new neurons can be targeted to specific areas of the brain.
Expected future outcomes:
Our identification of key molecular mechanisms that regulate brain functions associated with the production of
new neurons provides potential targets for the development of novel therapies to combat conditions such as
dementia, depression, and multiple sclerosis, which account for much of our socioeconomic burden of disease.
Name of contact:
Email of contact:
Professor Perry Bartlett
p.bartlett@uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
301298
Dr Rosa Alati
Epidemiology
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2004
2008
$260,000.00
Public Health (Australia)
Title of research award: Causal Pathways to mental health: a longitudinal investigation
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
I have advanced national and international understanding of causal pathways to mental health disorders,
particularly causal factors influencing substance use and the developmental origin of behaviour and mental health
problems. Since 2004, I have taken full advantage of the opportunity afforded by this NHMRC fellowship for fulltime research, national and international collaboration with outstanding research teams, to produce accellerated
research output. I have published 23 research papers during the 4 year duration of this fellowship. Firstly, I have
published on associations between early influences and a range of health and mental health problems, particularly
alcohol disorders. One paper published in the Archives of General has received 30 citations to date. Secondly I
have obtained a NHMRC Travelling Award, and spent 4 months at Bristol University (UK) and further studied the
contribution of pregnancy exposure to alcohol and adverse outcomes in children. This travel has allowed me to set
up important international collaborations. Finally I have used the last year of my fellowship to collaborate with
other outstanding groups in Australia in order to work on a range of Australian and UK cohort studies. By
working on different cohort studies and use them at their full capacity, it is possible to make cross-cohort
comparisons in order to develop a detailed understanding of the biological, individual and social causes and
consequences of alcohol problems at different stages of the life course.
Expected future outcomes:
I have been awarded a CDA fellowship to continue my work on life-course epidemiological analyses of alcohol
and other mental health disorders (using prospective longitudinal studies, and to investigate causal factors leading
to mental health disorders and receive further training in genetic epidemiology.
Name of contact:
Email of contact:
Rosa Alati
r.alati@sph.uq.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
351582
Dr Melissa R. Haswell-Elkins
Social and Community Psychology
University of Queensland
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$397,276.00
Standard Project Grant
Title of research award: Empowerment as a strategy for wellbeing in Indigenous settings: developing tools to
systematically evaluate outcomes
Lay Description (from application):
This project will add significant strength to one of Australia's key initiatives in the promotion of health and wellbeing, namely the Family Well Being Program . This program was developed by a group of Aboriginal people
based in Adelaide in order to specifically address the effects of colonisation on the emotional health and wellbeing
of Indigenous Australians. It is a nationally accredited course and has been delivered in a wide variety of settings
and participating groups. Previous evaluation using in-depth interviews, focus groups and course evaluation forms
have revealed long lasting increases in participants' life skills and problem-solving capacity, thereby making them
better able to help themselves and the young people around them to deal with emotions and life's challenges.
Changes are particularly profound among individuals who have completed the full Four Stage Program (40 week
course) and their families and communities. Up to now, the impact and outcome of the Family Well Being
Program has not had a way of being objectively measured in the way that other health promotion programs have.
This is partly due to the complexity of its aims; empowering people to take control of their lives, as opposed to
trying to directly change behaviours that place them at risk of illness. It is also because the definition, pathway and
results of becoming an empowered person, group and community are not completely understood and are likely to
be expressed differently from one social and cultural group to another. This current project aims to gain a clearer
understanding of the meaning, experience, outcomes and values people attach to empowerment; then use this
information to design tools to help assess the effectiveness of programs that seek to stimulate empowerment.
Activities will include further analysis of existing qualitative data, workshop discussions, piloting tools and
implementing them within communities with ongoing Family Well Being programs.
Research achievements (from final report):
Empowerment is a word frequently used across Australian Aboriginal heath and social policy as a means to assist
individuals and communities to gain greater control over their lives and situations and enable change. However, a
detailed Aboriginal definition of empowerment has not been identified and there was no literature on methods and
tools to measure it with this group. The aim of this project was to develop and test an instrument that enables
reliable measurement of valued aspects of movement from states of relative disempowerment towards
empowerment. To ensure the developing tool truly reflects Indigenous views and values, in depth interviews were
first analysed to gain a clearer understanding of the pathway, meaning, experience, outcomes and values that
Aboriginal people attach to empowerment. A format and set of questions to measure the major widely shared
components were developed and guided by consultations with groups of Aboriginal participants in Alice Springs,
Cairns, and Yarrabah communities and national experts in complex measurement. The resulting Growth and
Empowerment Measure (GEM) has two parts, namely a 14-item Emotional Empowerment Scale and 12 Scenarios
and is embedded in a metaphor of growth of a strong and healthy tree. The GEM was then trialled with 184
Indigenous Australians. Findings thus far suggest that the GEM has strong reliability and validity. Work is
continuing on its validation across contexts and with groups of both Indigenous and non-Indigenous people and on
its use in evaluating the impact and outcomes associated with empowerment programs.
Expected future outcomes:
This instrument contributes significantly to our ability to systematically evaluate empowerment interventions,
fostering the growth of evidence and cost-benefit analyses to quantify their value. It will enhance understanding of
social and emotional causes of distress and disadvantage and help identify ways to strengthen people's own
capacity to address them.
Name of contact:
Email of contact:
Melissa Haswell
m.haswell@unsw.edu.au
NHMRC Research Achievements - SUMMARY
University of Sydney
Grant ID:
153946
Start Year:
2001
CIA Name: Prof Iain S McGregor
End Year:
2003
Main RFCD: Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Total funding:
$206,320.45
Admin Inst: University of Sydney
Grant Type: Standard Project Grant
Title of research award: The Neurotoxic and Behaviourial Effects of MDMA ("Ecstasy")
Lay Description (from application):
MDMA (Ecstasy) has recently become one of the most popular recreational drugs in the world. A major concern
with MDMA use is the mounting evidence from animal studies that even moderate doses may cause irreversible
damage to nerve cells that utilize serotonin (5-HT) for neurotransmission. What is not known is how this damage
might be expressed in terms of altered emotion, cognition and behaviour. Existing evidence suggests an important
role for 5-HT in anxiety, depression and impulsiveness, but whether MDMA use will increase the likelihood of
such problems is uncertain. A major aim of this project is to examine the behavioural, cognitive and emotional
changes in rats following exposure to MDMA. Using a variety of sophisticated tasks, we will determine the acute
and the long term effects of MDMA in relation to memory, attention, impulsivity, and anxiety. A further concern
is whether MDMA use may increase vulnerability to the addictive effects of other drugs of abuse . We aim to
examine whether rats pre-exposed to MDMA are subsequently sensitised to the rewarding effects of cocaine and
opioids. MDMA users may also suffer a temporary depression a few days after taking the drug. We will assess the
possible anhedonic or depressing effects of MDMA. Finally, there is still a lot to understand about the way
MDMA affects the brain. Our recent work shows that many diverse brain regions are affected by this drug. We
want to extend this work to see how this pattern of brain activation is altered by fluid deprivation and high
ambient temperatures - conditions experienced at rave parties. The present project will help further our
understanding of MDMA and its neurotoxic effects and to highlight any potential long-term dangers to health that
may exist for people who are currently using or are planning to use this drug.
Research achievements (from final report):
N/A
Expected future outcomes:
This project provided important new information on the long term efects of the commonly used drug MDMA
("Ecstacy"). Our results showed conclusively a number of adverse consequences associated with even relatively
brief exposure to MDMA. This will inform the scientific and broader community of the possible hazards
associated with use of MDMA.
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
157158
Dr Peregrine B Osborne
Central Nervous System
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$435,956.26
Standard Project Grant
Title of research award: Forebrain neuroadaptations to chronic morphine treatment
Lay Description (from application):
Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal
behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that
behaviours relating to drug taking become associated with "feeling good". In some individuals, over time the
pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be
due to drugs causing physical changes to certain groups of nerve cells in the brain. The affected nerve cells are
responsible for causing new behaviours that appear once addiction is established. Addiction is not exclusive to
humans. Animals will self-inject the same addictive drugs that humans use, and show many other kinds of
addictive behaviours that parallel aspects of human addiction. Studying the effects of addictive drugs on rats and
other animals has been very important in working out where and how drugs work. We now have a very good idea
of which parts of the brain are affected by drugs, and it turns out that most addictive drugs act in the same places.
We also now know for all of the major drugs, exactly which parts of nerve cells they affect. However, this turns
out to be only the first step as the nerve cells that directly respond to drugs can affect other whole networks of
nerve cells. This study is going to look at how morphine, a drug that is related to heroin, affects nerve cells in a
part of the brain that helps cause addiction. It is going to work out which of the many pathways in this brain
region are affected by morphine treatments that cause addiction in rats. It will then see what is happening to single
nerve cells in the affected pathways. If we can understand more about these processes it may become possible to
come up with new ways to treat addiction. We will also understand much more about the production of powerful
emotional and behavioural drives so many of us find hard to control.
Research achievements (from final report):
This project has identified experimental methods using animals that can be used to investigate the biological basis
of addiction. It is generally accepted that drugs of abuse cause semi-permanent changes in brain function that
increase the risk of pathological uncontrolled drug taking, which can be reinstated even after prolonged periods of
abstinence. We now have the ability to induce behaviours associated with addiction, and detect corresponding
brain areas activated by these behaviours. These types of studies are progressively leading to scientific
understanding of the processes that maintain addiction, and should identify new approaches that can be used to
treat addiction and prevent relapse.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
153716
Prof Chris C Tennant
Psychiatry
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2001
2004
$298,511.00
Standard Project Grant
Title of research award: Depression and risk of coronary heart disease: a prospective study of mediating risk
factors
Lay Description (from application):
Growing evidence suggests that depression, anger and anxiety play a role in causing coronary heart disease (CHD)
and complicating the outcome in existing CHD. This may occur by effects of these emotions on promoting blood
clotting and the "stickiness" of platelets - the blood cells responsible for blood clotting. This pilot study will
follow a group of people with depression but without CHD and a control group over 8 months to compare how the
blood clotting profile changes as depression resolves. The potential benefits of this research are a better
understanding of the links between the common illnesses of depression and CHD that might improve the
prevention and treatment of heart disease.
Research achievements (from final report):
Increasing evidence has suggested that depression is an independent risk factor for Cardiovascular Disease
(CVD), although the mechanism has not been well understood. Since thrombosis plays a key role in CVD, with
new risk factors for heart disease such as fibrinogen emerging, we wanted to establish whether depression led to a
physiological state that might promote thrombosis and inflammation. We examined whether a group of 105
clinically depressed individuals had factors in their blood that would suggest a greater tendency to thrombosis and
inflammation when compared to a non-depressed control group. We also followed the depressed group over time
to see if treatment of depression reduced these risk factors. We measured serum fibrinogen, von Willebrand factor
(VWF) and Factor VII and the traditional risk factors of serum lipids (total cholesterol, HDL and triglycerides).
Preliminary results showed that those with depression had a higher serum fibrinogen than those who were not
depressed. After treatment, the depressed group lowered its fibrinogen significantly. VWF was also significantly
higher in the depressed group and lowered with teatment. Baseline serum lipids and FactorVII were not
statistically different. We concluded that Fibrinogen levels are increased in depression, and lowered with
treatment. Since Fibrinogen is an important risk factor for CVD, our data suggest that depression may contribute
to CVD through promoting inflammation and thrombosis and that alleviation of depression may reduce CVD
through beneficial effects on thrombosis and inflammation.
Expected future outcomes:
N/A
Name of contact:
Email of contact:
Dr Loyola Mclean
lmclean@med.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
211177
Prof Paul S Haber
Psychiatry
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2002
2004
$421,650.00
Standard Project Grant
Title of research award: The role of pharmacotherapy in prevention of relapse in alcohol dependence
Lay Description (from application):
The physical, psychological and social consequences of alcohol abuse remain a critical health problem. Every year
in Australia, excessive consumption is responsible for 3,000-6,000 deaths and costs the community $6 billion.
Approximately 15% of Australians abuse alcohol and 5% of men and 3% of women are alcohol dependent
(addicted to alcohol). Young men are particularly affected, with 10% of all men aged 18-35 dependent on alcohol.
Better treatment for alcohol dependence is urgently needed. Less severe forms of alcohol abuse frequently respond
to brief screening and intervention programs. Treatment of alcohol dependence remains unsatisfactory. Most
treatments lead to abstinence in only 1/3, and approximately 50% of these will relapse within 3 months of
completing treatment. Two drugs (naltrexone and acamprosate) appear to interfere with the effects of alcohol on
the brain that promote addiction. There is evidence that both drugs are beneficial in the treatment of alcohol
dependence and both are now available in Australia. At present, no data have been reported comparing the
effectiveness of these two drugs. The proposed project will compare naltrexone and acamprosate in a large
carefully performed study. The study will help determine which subjects are likely to benefit from one or other of
these agents. Compliance is a major problem with many medications, but is a particular problem with medications
for substance abuse. The second aim of this study is to test a novel intervention to increase compliance with
medications for alcohol dependent subjects. This intervention comprises 'compliance therapy', which resembles a
short training course, a medication alarm, and an assertive reminder program for scheduled medical appointments.
The present study will be the first to apply this type of therapy to subjects with alcohol dependence.
Research achievements (from final report):
This was the largest randomised control trial of pharmacothery for alcohol dependence ever conducted in
Australia. Across Sydney, 169 participants were recruited and given 12 weeks treatment with natlrexone,
acamprosate or placebo, in conjunction with Compliance Therapy, a behavioural intervention. Overall, particpants
showed an improvement in the amount of alcohol consumed and dependence severity following treatmenet.
However, no significant benefits were shown for either the naltrexone or acamprosate groups compared to placebo
controls. These results are consistent with a large recently published internatiol trial (COMBINE), which reported
similar outcomes. Notwithstanding, further examination of the data supported the efficacy of naltrexone in the
relapse prevention of alcohol dependence amongst those with low levels of clinical depression and alcohol
dependence severity. Compliance Therapy was also found to significantly improve rates of treatment adherence.
The results of this clinical alcohol dependence study are a valuable step toward finding more effective treatments
for this complex and widespread condition.
Expected future outcomes:
The Sydney Alcohol Treatment Research Group aims to further investigate the complicated nature of relapse
prevention in alcohol dependece and the variability of treatment responses by focusing research on: i) the
concurrent treatment of comrbid anxiety and depression, ii) genetic markers linked to treatment response, and iii)
novel pharmacotherapies.
Name of contact:
Email of contact:
Paul Haber
phaber@mail.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
302007
Dr Brian I. O'Toole
Epidemiology
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2004
2005
$0.00
Standard Project Grant
Title of research award: The Australian Vietnam Veterans Health Study; Cohort Wave 2
Lay Description (from application):
Military records show that Australia has committed troops to war since the time of the Boer War, continuing
commitments through World Wars I and II, the Korean War, the Malaya Emergency, the Vietnam Conflict, the
Gulf War, and numerous peacekeeping operations across the world, yet there has never been an epidemiological
cohort study that tracked the path of their health and their lives after their return. This study will provide an
approximate 10-year followup of an established cohort of Australian Vietnam veterans, which was the first such
study ever conducted of returned Australian servicemen. It will test diagnostic stability and chart the trajectory of
health and welfare over time in the men and relate this to possible causal determinants including military service,
combat deployment and trauma exposure, post traumatic stress disorder and alcohol disorders. It will also allow us
to examine the role of their previous health state, determined 10 years ago, in relation to their current health state.
Data and methodology from the Australian Bureau of Statistics national surveys on physical and mental health
will be incorporated so that comparisons can be made with Australian population data for the study group.
Significantly, wave 1 preceded automatic compensation for veterans for cancer and PTSD; provoked the DVA's
national survey that led to a $32M government program response; fed into the DVA mental health policy; fed into
the Army selection guidelines for overseas service via the Psychology Corps; fed into DVA policy re Vietnam
Veterans Counselling Service. Wave 2 will continue this informative process as the cohort ages. This study will
provide a firmer basis for treatment of war veterans and others whose lives are visited by trauma, physical illhealth, alcohol disorders, or mental health problems in adulthood.
Research achievements (from final report):
This study has assembled information on the long term effects of war service on the soldiers themselves that will
enable decision- makers to ensure that future Australian warriors are cared for appropriately according to their
circumstances and history of trauma. The study will contribute to the understanding of the long term physical and
mental health effects of exposure to extreme psychological trauma.
Expected future outcomes:
Publications on the findings from an examination of the longitudinal course of post-traumatic stress disorder and
the long term physical and mental health consequences of traumatic exposure.
Name of contact:
Email of contact:
Dr Brian O'toole
botoole@med.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
301908
Prof Michael Murray
Basic Pharmacology
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$330,375.00
Standard Project Grant
Title of research award: Clozapine toxicity: Role of pharmacogenetic variation in CYP enzymes and
bioactivation mechanisms in patient neutrophils
Lay Description (from application):
The treatment of mental disorders such as schizophrenia involves the administration of potent drug combinations
to patients. Some individuals, however, do not respond to commonly-used antipsychotic drugs and their condition
only improves with a unique drug called clozapine. The major problem with clozapine is its toxicity toward blood
cells, heart and other organs. All people who receive clozapine must be monitored closely, especially in the first 34 months after starting therapy. Several new drugs have been suggested to be safer versions of clozapine but these
are all ineffective. Clozapine is the only agent that is effective in people who do not respond to the other drugs
used to treat schizophrenia. Thus, clozapine toxicity, which necessitates discontinuation of the drug, is a
devastating outcome because there is no alternative treatment that is available. Another significant problem with
clozapine is that its rate of removal from the body is slowed down by many other drugs that are used concurrently.
The problems with clozapine occur in some but not all individuals. This suggests that the patient's genetic makeup
and their exposure to drugs and environmental agents determine the incidence of toxicity. The present project
looks at how clozapine is removed from the body and how it is converted into a toxic product that damages cells.
These processes will be examined, with emphasis on differences between individual patients, and strategies to
protect cells from damage from the toxic derivative will be tested. Corresponding studies will be done in patients
who are receiving clozapine as treatment for psychoses. We will be able to compare experimental and clinical
findings in order to identify those patients who appear to be at risk. This will be possible before the toxic effects
occur and will help us to identify subjects in whom the drug should only be used with great care. We may also
devise strategies that will minimise the incidence of toxicity.
Research achievements (from final report):
Many psychiatric patients are resistant to conventional antipsychotic drugs but respond to the atypical agent
clozapine; however, serious adverse effects lead to termination of clozapine therapy. The hypothesis underlying
this project is that, because cytochrome P450 (CYP) is critical in clozapine elimination, individual variation in
CYP function may contribute to toxicity. This project evaluated how CYP gene makeup affects the safety and
efficacy of clozapine in patients, and the incidence of drug interactions. Achievements to date: We have developed
a novel, high-throughput LC-MS method for simultaneous phenotyping of major CYPs for use in clinical studies.
This will aid in the individualisation of dosage of toxic drugs in patients. We have recruited >50 patients,
undertaken in vivo CYP phenotyping and genotyped for several CYP1A2 and CYP3A4 variants. Caffeine
clearance (CYP1A2 substrate) and clozapine serum levels were correlated in these patients. We have identified
several problem and safe drug combinations in clozapine-responsive patients. We have identified a patient with a
novel CYP1A2 gene variant who has been difficult to control on clozapine. The same haplotype has also been
detected in our liver bank; we are now completing a functional analysis.
We have completed an in vitro
evaluation of the role of CYP gene variants in clozapine metabolism. Our available liver bank has been screened
for clozapine oxidation capacity, in relation to CYP content. Although CYP1A2 is the principal clozapine oxidase,
CYP3A4 is functional in a number of samples. This information is being used to establish the criteria for the
incidence of CYP-based drug-drug interactions involving clozapine.
Expected future outcomes:
Appreciation that differences in CYP pathways of clozapine clearance may precipitate pharmacokinetic
interactions with some drug combinations in those individuals. Potential application of a rapid profiling technique
for phenotyping patients CYP clearance pathways in vivo for use in personalised medicine regimen.
Name of contact:
Email of contact:
Michael Murray
michaelm@pharm.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
253836
A/Pr Thiagarajan Sitharthan
Mental Health
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2003
2007
$340,000.00
Standard Project Grant
Title of research award: A controlled trial of an opportunistic intervention to reduce suicide risk among alcohol
and other substance misusers
Lay Description (from application):
Hopelessness, depression and suicidal ideation are common among people who misuse alcohol and other
substances. A general relationship between alcohol/substance abuse and self-harming / suicidal behaviour has
been recognised for decades. From the point of view of diagnosed substance abusers there is a correspondingly
high incidence of suicide and self-harm. The lifetime risk for suicide in alcohol dependence is higher than for
schizophrenia or affective disorder. Despite the public health and personal burden associated with suicidality, the
general lack of skills and focus on management of self-harm in specialised drug and alcohol services is of great
concern. In this study, all patients attending drug and alcohol services will be screened for suicide risk, and
offered a comprehensive psychological treatment to reduce suicide risk and the use of alcohol and other
substances.
Research achievements (from final report):
This project created an awareness among clinicians to target depression, hopelessness, and suicide risk among
alcohol and substance misusing populations. In particular, the clinical trial demonstrated that such negative
emotions can be modified via psychological interventions and assist in reducing alcohol / substance misuse.
Clinical assessment measures and clinical treatment manuals developed for the trial are used as part of training the
workforce and has led to improvements in service delivery. Papers are prepared for publication.
Expected future outcomes:
We plan to conduct clinical workshops to assist clinicians to be better aware and more skilled in the detection and
management of depression and suicide risk among alcohol / substance misusers. To publish results in peerreviewed journals.
Name of contact:
Email of contact:
A/Prof T.Sitharthan
thiagarajan_sitharthan@wsahs.nsw.gov.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
352475
Prof Iain S McGregor
Central Nervous System
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$379,000.00
Standard Project Grant
Title of research award: Ecstasy, methamphetamine and their combination: Assessment of adverse effects.
Lay Description (from application):
MDMA ("Ecstasy") and Methamphetamine ("METH") are popular party drugs that are frequently used by young
Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications
arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may
both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to
psychological problems such as anxiety, depression, increased impulsive behaviour and memory impairment.
However the link between MDMA and METH use and subsequent brain damage is still very controversial.
Recently, we have found that when MDMA and METH are combined, a particularly toxic effect is seen with very
high body temperatures and lasting adverse effects on mood and brain function. This is a major cause for concern
because of evidence that many Australian drug users are combining METH and MDMA on a regular basis. This
project will investigate the short and long-term effects of MDMA, METH and METH-MDMA combinations.
Phase 1 is aimed at investigating whether different doses of the drugs lead to lasting changes in mood, behaviour
and brain function and to compare the relative toxicity of the three treatments. Phase 2 will determine whether
lack of fluid intake, high environmental temperatures and advanced age are risk factors in determining the toxicity
of MDMA and METH. Phase 3 will assess whether the toxicity of these drug treatments depends upon whether an
animal takes the drugs voluntarily or whether they are injected with the drug by the experimenter. The final part of
the project will use a wide variety of advanced techniques to track the brain damage caused by these drug
treatments given under a range of conditions. The significance of this project will be in increasing our
understanding of how MDMA and METH affect the brain and behaviour and how the harms posed by these drugs
may be predicted and therefore minimised.
Research achievements (from final report):
This project used animal models to characterize the long-term adverse effects of MDMA ("Ecstasy") and
methamphetamine on the brain and behaviour. The possibility that the combination of these two drugs might be
particularly toxic to the brain was of major interest. The research project was successfully concluded and gave rise
to numerous publications in good journals. Major findings included: Enhanced toxicity of MDMA and
methamphetamine when they are combined, relative to when they are given alone. High ambient temperatures
enhance the rewarding effects of methamphetamine, and greatly increase the impact of both MDMA and
methamphetamine on the brain. An acute impairment of memory with MDMA, that is exacerbated by cannabis.
Demonstrating major proteomic changes in the striatum of rats given either acute or repeated exposure to
methamphetamine. The release of the neuropeptide oxytocin underlies the effects of MDMA on "love" and
"sociability".
Expected future outcomes:
A new NHMRC project grant commenced in 2008 to continue research in this area and follow up on findings of
neuropeptide involvement in MDMA and methamphetamine effects. Other research groups around the world have
also commenced research arising from this discovery.
Name of contact:
Email of contact:
Iain Mcgregor
iain@psych.usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
302101
Start Year:
Prof Mark Onslow
End Year:
Rehabilitation and Therapy: Hearing and Speech
University of Sydney
Grant Type:
2004
2008
Total funding: $713,750.00
NHMRC Research Fellowship
Title of research award: Principal Research Fellow and Support Enhancement Option
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
The award of this Fellowship allowed Professor Onslow to work as Director of the Australian Stuttering Research
Centre at The University of Sydney as a research-only academic. This permitted him, for the tenure of the grant
during 2004-2008, the necessary focus to attract $6.3M of research external funding, most notably $4.4M as
leading investigator on NHMRC Program Grant 402763. The Fellowship also allowed Professor Onslow to
establish a national and international research collaboration network. This research funding has tripled the
research productivity of the research team Professor Onslow leads, and has established significant advances in the
health care of children and adults who stutter. These include (1) new treatments for preschoolers, (2) telehealth
treatment for adults and children so that face to face patient-clinician contact is not necessary, (3) the first
randomised controlled trials of treatments for adults and children, (4) discovery of the mental health problems
faced by adults to stutter and development of a way to treat them effectively, (5) the first accurate estimate of the
prevalence of stuttering in preschool children and its impact on them, and (6) development of a new theory about
the cause of stuttering that has potential impact on treatment development.
Expected future outcomes:
These research advances provide a foundation for a comprehensive future research program led by Professor
Onslow at the Australian Stuttering Research Centre. That program of research will develop Internet based
treatments for the speech and mental health rehabiliation of those who stutter, and for the prevention of the
disorder in preschool children.
Name of contact:
Email of contact:
Professor Mark Onslow
m.onslow@usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
358676
Dr Kim L Felmingham
Mental Health
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
Fellowship
2005
2009
$264,000.00
Australian Clinical Research
Title of research award: Acute predictors of Chronic Posttraumatic Stress: An integrative fMRI and autonomic
study.
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
I achieved several major outcomes during my NHMRC postdoctoral fellowship, including the publication of 25
peer-reviewed journal articles since 2005, the award of three major research grants including an NHMRC Project
Grant and an ARC Discovery Grant to examine mechanisms underlying Posttraumatic Stress Disorder (PTSD),
and an ARC Discovery Grant to examine the neurobiological specificity of anxiety and depression, an academic
promotion and an invitation by the Thai Government to train mental health professionals in exposure-based
treatment to assist tsunami survivors. A major research outcome was the publication of the first research
examining neurobiological mechanisms underlying successful exposure-based treatment in PTSD. This series of
publications identified neurobiological mechanisms associated with improvement of PTSD, and neurobiological
predictors of cognitive behavioural therapy (CBT) treatment response . This research revealed that heightened
activity in fear networks (the amygdala) and reduced volume in prefrontal inhibitory networks (the anterior
cingulate cortex) predicted poorer response to CBT exposure treatment, and that successful treatment response
was associated with reductions in amygdala fear networks and increases in prefrontal inhibitory networks. This
research provides an important validation of current neurobiological models and the proposed mechanisms
underlying exposure treatment. I also published the first research examining an important clinical sub-type of
PTSD, dissociative PTSD, in response to subliminal fear stimuli , and I developed novel integrative fMRI and
autonomic analysis techniques to examine the role of physical arousal in determining brain responses in PTSD.
Expected future outcomes:
In the past two years, i have expanded my research to include genetic, neurocognitive and electrophysiological
data that will identify further genetic, cognitive and neurobiological mechanisms underlying successful treatment
of PTSD. I have also expanded my neuroimaging research to examine memory suppression, emotion regulation,
D-Cycloserine and Glutamate in PTSD.
Name of contact:
Email of contact:
Kim Felmingham
kfelmingham@usyd.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
358770
Dr Andrew H Kemp
Mental Health
University of Sydney
Start Year:
End Year:
Total funding:
Grant Type:
2005
2009
$264,000.00
Peter Doherty Fellowship
Title of research award: Predictors of response to antidepressants: evidence from clinical, psychometric,
neurogenetic and neuroimaging measures
Lay Description (from application):
No available Lay Description
Research achievements (from final report):
I achieved a number of major outcomes while holding my postdoctoral research fellowship including publication
of 36 peer-reviewed journal articles since 2005, the award of two major research grants including an NHMRC
Project Grant and an ARC Discovery Project that relate to the broad goals of my fellowship and an academic
promotion. A major research achievement was the elucidation of gene-brain-behavioural pathways specific to
depression and anxiety. This outcome determined differential gene-brain-behavioural pathways that lead to
depression and anxiety, and findings have recently been published in Molecular Psychiatry (impact factor =
10.900). This study demonstrated that BDNF met carrier status and exposure to early life stress predicts reduced
gray matter in hippocampus and associated lateral prefrontal cortex and in turn, higher depression. By contrast, the
combination of BDNF V/V genotype and early life stress predicted increases in gray matter of amygdala and
associated medial prefrontal cortex, which in turn predicted startle-elicited heart-rate variability and higher
anxiety, highlighting partially differentiated pathways for depression and anxiety. Another major research
achievement was the publication of the first review paper to comprehensively review the literature on the
prediction of treatment response in depression. I have recently been awarded an NHMRC Career Development
Award to allow me to continue my research into depression and its treatment.
Expected future outcomes:
Currently, I am conducting a number of studies which seek to better understand the neurobiological correlates of
depression and anxiety, and their treatment. I have also taken up a new research-only position in the School of
Psychology at the University of Sydney, which will allow me to setup my own laboratory and further develop my
research activities in this area.
Name of contact:
Email of contact:
Andrew Kemp
akemp@usyd.edu.au
NHMRC Research Achievements - SUMMARY
University of Western Australia
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
139123
Prof Leon Flicker
Geriatrics and Gerontology
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2001
2003
$286,018.36
Standard Project Grant
Title of research award: An Intervention Trial to Prevent Cognitive Impairment and Depression in Older Men
Lay Description (from application):
A gradual decline in the thinking processes, dementia and depression are major health issues for older people.
There is already some evidence that deficiency in certain vitamins may be contributing to these problems. This
project seeks to evaluate an inexpensive and simple vitamin supplement which may provide a highly costeffective method of preventing cognitive decline, dementia and depression in older people. This research will also
allow the evaluation of the role of certain biological and genetic risk factors which may also impact on these
problems. This project seeks to do a trial of these vitamins in older men who are at particular risk for these
problems. The men in this project will be monitored by simple tests of their thinking and evaluating any
symptoms of depression.
Research achievements (from final report):
It is a little early and will depend on the outcome of the analyses once the full analyses have taken place (we still
have not unblinded). Others have demonstrated that there is an association between the toxic protein homocysteine
in the blood and the important problems of depression and memory problems in older people. We have
demonstrated that there are high rates of B12 deficiency and elevated levels of homocysteine in well older men.
We are currently waiting for the results of our study to see if vitamin supplements can correct some of these
problems
Expected future outcomes:
N/A
Name of contact:
Email of contact:
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
254518
Prof Gary K Hulse
Mental Health
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2003
2003
$111,625.00
Standard Project Grant
Title of research award: Effect of naltrexone treatment on health outcomes and health service utilisation : a
record linkage study
Lay Description (from application):
Research has shown that heroin use is an increasing habit of Australia's youth with morbidity and mortality rates
for regular heroin users significantly greater than that for the general population. Despite the introduction of a
number of treatment options to combat the problem, the management of dependent heroin use has proved
problematic. This application addresses an issue of considerable importance and controversy in recent years,
namely, the impact of naltrexone and methadone treatment on morbidity and mortality among persons who are
heroin dependent. The study will be carried out using a unique system of linked hospital records from the Western
Australian Health Services Research Linkage Unit at the Department of Health Western Australia (DHWA).
Through this system hospital, mental health and death records derived from different sources, but related to the
same individual are electronically linked. Hence, record linkage provides an independent method for obtaining
information on treatment outcomes which is free from subjective bias. In the current study records from heroin
users who entered naltrexone maintenance and a smaller group who entered methadone maintenance will be
linked to the DHWA database. Collectively these data will be used to quantify morbidity, hospital episodes,
mental health issues and mortality in heroin users following commencement of naltrexone maintenance treatment.
Data will also be used to compare positive and negative outcomes for individuals on naltrexone with those on
methadone. The results will be used to advocate on behalf of this vulnerable population in a country that prides
itself on universal access to high quality health services. It is anticipated that this study will have a substantial
beneficial impact on the management of illicit drug use policy and as well as contributing new research methods,
findings and international knowledge.
Research achievements (from final report):
The study used records from heroin users who entered oral naltrexone treatment and a smaller group who entered
methadone treatment and linked these to general and mental health hospital admission data from the Health
Department.The study used this linked data to look at outcomes associated with treatment over a six year period (3
years before treatment and 3 yers after treatment). Results of mental health outcomes were most notable in that the
rsik of mental health admissions increased in the 3 months before treatment regardless of the subsequent treatment
type entered. This suggests that treatment for heroin addiction in this group is a form of crisis intervention. Risk of
mental health admission decreased within 6 months after treatment. No notable trend was observed with general
hospital admissions. While there was a reduction in narcotic and opioid poisonings, sedative and hypnotic
poisonings increased 6-18 months post treatment. With regard to naltrexone treatment specifically, those who
remained on oral naltrexone at 6 months post treatment entry were more likely to remain heroin free in the 12
months following treatment. In the 31-35 year age group of heroin users risk of hospital admission increased.
Carer suppport and whether a partner was also on naltrexone maintenance treatment determined whether persons
were successful on the oral naltrexone maintenance programme.
Expected future outcomes:
The predictors of better treatment outcome can be used to better structure heroin treatment programmes
incorporating naltrexone maintenance. The results show overwhelmingly the co-existence of non-drug related
mental helath disorders with drug related mental helath disorders. It is envisaged that future publications will
highlight this unrecognised link.
Name of contact:
Email of contact:
Prof G K Hulse
ghulse@cyllene.uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
303172
Prof Nicola T Lautenschlager
Geriatrics and Gerontology
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2004
2006
$274,625.00
Standard Project Grant
Title of research award: A randomised trial of physical activity for the treatment of older adults with mild
cognitive impairment
Lay Description (from application):
Australia's population is aging rapidly and so is the frequency of age-related diseases. Dementia and depression
are the most frequent mental health disorders of older people. They are also the leading causes of years of life lost
due to disability in Australia. The results of recent studies have shown that memory difficulties and dementia are
associated with potentially modifiable risk factors, such as physical activity. The purpose of this study is to
investigate whether a physical activity program for older adults decreases cognitive decline and conversion to
dementia in a population at risk: mild cognitive impairment (MCI). 168 subjects with MCI will be randomised (by
chance, like the flip of a coin) to either the intervention program of physical activity or usual care - their cognitive
(such as memory) performance will be compared at the end of 24 months.
Research achievements (from final report):
Data collection for this trial has been completed in January 2007. Preliminary results of ths study show that
participants, who were randomised to the intervention, could complete the physical activity program successfully.
After completion of the intervention they were significantly more physical active than the control group and they
also performed significantly better on cognitive tests.
Expected future outcomes:
To promote phsycial activity as a lifestyle intervention which can positively affect cognitive function in older
adults with memory complaints.
Name of contact:
Email of contact:
Prof Nicola Lautenschlager
nicola.lautenschlager@uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
303106
Start Year:
Prof Gary K Hulse
End Year:
Medical and Health Sciences not elsewhere classified
University of Western Australia
Grant Type:
2004
2007
Total funding: $558,675.00
Standard Project Grant
Title of research award: A randomised double blind controlled clinical trial of naltrexone implants for the
treatment of heroin addiction
Lay Description (from application):
GoMedical Industries has developed a formulation of sustained release naltrexone, suitable for subcutaneous
depot administration (International Patent Application Number: PCT/AU01/01107, GoMedical Industries Pty Ltd,
Australia). Currently, implants are inserted by minor surgery under local anaesthetic in high risk patients under the
Therapeutic Goods Administration (TGA) Special Access Category A scheme (SAS) through the Australian
Medical Procedures Research Foundation (AMPRF), Western Australia. Although there is a preliminary basis for
believing that this naltrexone implant treatment may offer significant benefits over oral and other naltrexone depot
preparations thus far reported for managing the heroin dependent patient, this needs to be verified through an
empirically designed study such a clinical trial. Lack of complete Commonwealth TGA approval to date has been
a major impediment to widespread adoption of this naltrexone preparation as an alternative treatment. Hence, the
main objective of this study is to provide rigorous clinical data on the efficacy of this naltrexone implant
compared to oral naltrexone in the management of heroin dependent persons by primarily monitoring:
Maintenance of blood naltrexone and 6-b-naltrexol concentrations above therapeutic levels Retention in treatment
assessed by detection of blood naltrexone or 6-b-naltrexol Reduced frequency and quantity of opiate use
Prevention of accidental opiate overdose Reduced opiate related morbidity and mortality Reduced craving for
heroin and secondarily monitoring: Frequency and quantity of other drug use Other drug related accidental
overdose, other morbidity or mortality Level of social functioning . General health Monitoring of implant
insertion site healing
Research achievements (from final report):
Background: Naltrexone can block the actions of heroin; but its utility is limited by patient non-compliance with
oral dosing: sustained release preparations may overcome this limitation. This study assessed the safety and
efficacy of a sustained release naltrexone implant. Methods: Seventy heroin dependent (DSM-IV opioid
dependence) volunteers in Perth, Western Australia entered a randomized double-blind, double-placebo controlled
trial. Participants received 50mg oral naltrexone (plus placebo implants) or 2.3g naltrexone implant (plus placebo
tablets) with evaluation to six months. The main outcomes were: 1a) return to regular heroin use (≥4 days per
week); 1b) abstinence from illicit heroin/opioid use (self-report supported by urine testing); 2) use of illicit nonopioid drugs; 3) adverse events, and 4) blood naltrexone and naltrexol levels associated with naltrexone implant
treatment. Results: Significantly more of the oral than the implant naltrexone condition (59% vs 20%) returned to
regular heroin use by six months, and did so earlier compared to those receiving implant naltrexone (median 117
versus 161 days). Use of non-opioid drugs was similar for the two groups. There were ten trial related unexpected
adverse events such as diarrhea (oral 4 versus implant 6). One serious adverse event (wound hematoma) was
associated with surgical implantation. Blood naltrexone concentration was maintained above 2ng/ml and 1ng/ml
for approximately 60 and 108 days, respectively, for males, and 54 and 129 days, for female naltrexone implant
recipients. Conclusions: The implant formulation was not associated with major adverse events, effective in
retaining patients in treatment, with improved efficacy compared to oral naltrexone.
Expected future outcomes:
A large proportion of the implant naltrexone group were heroin abstinent/not using heroin regularly to six months,
with the potential that this type of treatment might significantly impact on the longer term prognosis for heroin
dependent persons, with heroin dependence no longer regarded as a chronic relapsing disorder.
Name of contact:
Email of contact:
Professor G.K Hulse
hulseg@meddent.uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
303235
Prof Assen V Jablensky
Psychiatry
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$442,875.00
Standard Project Grant
Title of research award: Fetal origin of adult disease? A population-based study of the offspring of women with
severe mental disorders
Lay Description (from application):
Fetal origin of adult disease is a currently influential paradigm in epidemiological research into common diseases
(ischaemic heart disease, hypertension, diabetes) and behaviour problems (suicide, criminal offending). It
postulates an early pathophysiological "programming" of outcomes that become manifest in adult life. In the
proposed research we aim to examine key aspects of this model by conducting a population-based study on the
developmental outcomes, antecedent and concomitant risk factors, and a spectrum of neuropsychiatric morbidity
in all children (N=5150) born in Western Australia in 1980-2001 to women diagnosed with schizophrenia, bipolar
affective disorder or unipolar depression, as compared to children (N=504,553) born to women without a
diagnosed psychiatric illness. The study will be based on record linkage, utilising the unique resource of multiple,
comprehensive population databases in Western Australia. Specifically, this research will identify the range of
developmental outcomes and morbidity in four consecutive birth cohorts (1980-84; 1985-89; 1990-94; and 19952001) of children at high genetic and environmental risk and examine their relationship to specific risk factors,
including familial genetic load, obstetric complications, severity of maternal illness, and psychosocial adversity.
The study will be the first of its kind and its findings will inform aetiological research into the major mental
disorders, as well as clinical and public health practice. It will provide novel data on fundamental issues, such as
the interaction between genetic risk and environmental factors in the causation of schizophrenia, as well as on the
extent to which the risk of developing severe mental illness is immutably embedded in its fetal origin, or is
modifiable by subsequent mitigating factors and appropriate intervention.
Research achievements (from final report):
This study investigated neuropsychiatric outcomes for a cohort of children of women with schizophrenia, bipolar
disorder and unipolar depression and compared these with outcomes for a comparison group of children. It has
provided novel data on fundamental issues, such as the interaction between genetic risk and environmental factors
in the causation of schizophrenia. Our data suggest these high risk children of women with severe mental illness
have a biological predisoposition to schizophrenia and some other neuropsychiatric outcomes. However, our
results also indicate that modifiable risk factors also contribute to these outcomes. This highlights the importance
of providing appropriate psychosocial interventions for these vulnerable women with psychosis in their pregnancy
period to reduce risk factors for adverse outcomes for their offspring. To this end, a pilot intervention program for
these women has been funded by the Department of Health as a follow-up to this research.
Expected future outcomes:
We have additional funding from NHMRC to continue to investigate outcomes for these high risk children.
Results from the current project have helped us develop specific hypotheses for testing.
Name of contact:
Email of contact:
Prof Assen Jablensky
assen@cyllene.uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
303251
Prof Dieter B Wildenauer
Psychiatry
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2004
2007
$457,750.00
Standard Project Grant
Title of research award: From linkage to genes conferring susceptibility to schizophrenia: investigation of
candidate genes on chromosome 6p
Lay Description (from application):
Schizophrenia is a potentially disabling disorder with severe impact on the individual, the family and the
community. The risk that a child born today will develop schizophrenia is about 1%. Genetic factors play a major
predisposing role in schizophrenia, but environmental factors contribute as well. The molecular causes of
schizophrenia are yet to be discovered, as knowledge about complex brain functions and their disorders is rapidly
increasing. The identification and characterisation of genetic factors involved in brain function and dysfunction is
likely to bring about novel insights into the neural and molecular mechanisms underlying schizophrenia. There is
evidence, reported by several groups including our own, that genes, co-segregating with schizophrenia in families
are located in a region on chromosome 6p. By fine-grain genetic dissection of this region, we and others have
found that the gene coding for the protein dysbindin is associated with schizophrenia. Our aim is to identify the
DNA variant(s) in the dysbindin gene, as well as variants in other candidate genes that may be located in
chromosome 6p. We will use state-of-the art methods and information on genes and DNA variants, made available
through the Human Genome Project. Once genetic variants are identified, we will analyse gene expression in post
mortem brain tissue of persons with schizophrenia and study the distribution and function of the proteins coded by
the identified genes. Our ultimate goal is to identify specific genetic factors involved in the brain dysfunction
characterising schizophrenia. If successful, this should lead to clues about the causes of the disorder. In addition,
the study will contribute to the development of methods for early diagnosis and prevention. Possibly, the most
important outcome will be the identification of molecular targets for novel and more specific pharmacological
treatments that may eventually replace current symptom-oriented antipsychotic medications.
Research achievements (from final report):
Schizophrenia is a severely disabling disorder which occurs at comparable incidence rates in diverse populations
and, with a lifetime risk of about 1% worldwide. Epidemiological studies provided convincing evidence that
genetic factors play a role in the development of schizophrenia, in concert with factors from the environment. In
this project we have been focusing on genetic factors located on chromosome 6 of the human genome. We have
been able to show, that factors located in the region contributing to immune response might explain some of the
genetic risk for schizophrenia. In addition, another factor, dysbindin, located relatively close to the immune
response region has been screened for schizophrenia risk contributing variants. It has been revealed that this gene
might put individuals at risk for development of schizophrenia. However, no clear cut relationship between
alteration in these genetic factors and altered function important to schizophrenia has been established yet. This
will be a crucial point facilitating the development of new targets for novel treatment options.
Expected future outcomes:
Our research is the basis for the identification of the relationship between the genetic findings and the protein
network these genes are acting together. This will enable new treatment options, including development of drugs
targeting the causes of schizophrenia.
Name of contact:
Email of contact:
Dieter B Wildenauer
dieter.wildenauer@uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
353569
Prof Osvaldo P Almeida
Mental Health
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$753,275.00
Standard Project Grant
Title of research award: Reducing depression and suicide amongst older Australians: a clustered randomised
clinical trial in primary health care
Lay Description (from application):
Like many industrialised nations, Australia's population is ageing. By the year 2051, the population aged 65 years
and over is projected to triple in size, while those over 85 will increase five-fold. The social, financial, and health
consequences of a rapidly ageing society cannot be ignored. Accompanying this population explosion will be
greater numbers of individuals experiencing age-related physical disorders and disabilities that give rise to social
and psychological problems, including depression and suicide. Suicide rates are very high in later life, with the
ratio of men who kill themselves in late old age greater than that found in their youthful counterparts. Depression
is most often linked to suicidal behaviour in this age group, with research suggesting that the treatment of this
mental disorder may directly lead to a reduction in suicide in the aged. Approximately 80% of older adults will
visit their general practitioner at least once per year in Australia, while up to 70% of older people will consult their
GP in the month prior to their death by suicide. This suggests that GPs are in the best possible position to detect
and manage depression and suicide risk in later life. Unfortunately, depression is consistently reported to be
underdiagnosed and undertreated in this setting. The purpose of this study is to determine whether an educational
programme targeting Australian GPs can enhance doctors' detection rates of depression and suicide risk, thereby
leading to a reduction in depression and suicidal behaviour among those older patients visiting their surgeries.
Research achievements (from final report):
At the time of writing, 16 publications have arisen from this project, with another 4 planned for the upcoming
year.
Expected future outcomes:
The final results of the trial have not been analysed yet. Data collection was completed in January 2009 and this
last database is now being cleaned and prepared for merging with existing databases. As previously stated, we
plan to draft another 4 papers over the next 12 months.
Name of contact:
Email of contact:
Osvaldo P. Almeida
osvaldo.almeida@uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
353648
Prof Luba V Kalaydjieva
Genetics not elsewhere classified
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2005
2007
$452,250.00
Standard Project Grant
Title of research award: Bipolar affective disorder in a genetic isolate
Lay Description (from application):
Bipolar affective disorder (BP), or manic-depressive illness, is a major cause of disability and mortality
worldwide. It has a lifetime prevalence of about 1% and suicide risk of about 20%. The disorder is characterised
by episodes of mania or hypomania and depression, appearing in varying succession, with or without intermission.
Twin, family, and adoptive studies point to a strong genetic component leading to the development of bipolar
disorder, with a heritability of the order of 80%. Yet the identification of the genetic basis of the disease has
proved exceedingly difficult, with numerous studies producing no definitive data. The lack of convincing results
has been interpreted as an indication of complex genetic mechanisms and underlying differences between affected
families and ethnic groups. Genetically isolated populations, where most individuals descend from a small number
of founders, are believed to hold great potential for understanding the genetic basis of complex diseases, such as
bipolar disorder. Affected subjects in such populations are likely to share the same predisposing genes, making
these genes easier to identify. During the last 10 years, we have been involved in the study of bipolar disorder in
one such population, with very promising results. In this project, we propose to take the research further by
collecting more affected families, confirming the current positive findings and narrowing down the search to a
small region, possibly a single gene. If successful, the study will be a major breakthrough which, by identifying a
molecular pathway and disease mechanism, will contribute valuable and generally valid information on the
biological basis of mood disorders.
Research achievements (from final report):
This study examined the genetics of bipolar affective disorder (BPAD, or manic-depressive illness, a major cause
of disability and mortality worldwide. A strong genetic component contributes to this condition, however attempts
to identify the genes have met with limited success, with genetic heterogeneity (i.e. multiple diverse genes of
small individual effects) commonly invoked as the explanation. Our project aimed to reduce genetic heterogeneity
to a minimum: examined one of the largest known affected families, originating from a small subisolate within a
larger isolate of limited diversity. We found no evidence of susceptibility variants shared between significant
numbers of the affected family members. The data point to phenotype definition and clinical heterogeneity as the
major confounding factor in BPAD genetics.
Expected future outcomes:
In BPAD, as in other phsychiatric disorders, attention is turning to the use of "endophenotypes" instead of broad
clinical diagnostic categories - measurable biological traits which should be intermediate between clinical disease
and genetic variants (e.g. individual cognitive functions, sleep patterns etc.). Although very labour-intensive, this
approach is likely to be much more productive.
Name of contact:
Email of contact:
Luba Kalaydjieva
luba@cyllene.uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
353545
Prof Gary K Hulse
Mental Health
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$212,325.00
Standard Project Grant
Title of research award: Assessing Naltrexone Implant or Methadone Maintenance Treatment on Mental &
Physical Health Outcomes in Heroin Users
Lay Description (from application):
The WA hospital data linkage system (DLS) will be used to assess differences in the mental & physical health of
dependent heroin users prior to & post naltrexone implant or methadone maintenance treatment (MMT). MMT is
the best established pharmacotherapy for the management of heroin dependence but oral naltrexone is gaining
some acceptance. Currently funded by NHMRC, we are looking at outcomes with oral naltrexone using DLS data.
Although effective in blocking heroin, management via oral naltrexone has proved problematic, with medicine
non compliance & relapse common. Surgical insertion of subcutaneous implants is an alternative method of
naltrexone delivery. 441 heroin users have received naltrexone implants (3.4g) under Special Access in WA.
Although naltrexone implants have yet to be comprehensively assessed, early results are encouraging. Pilot study
data has shown a significant reduction in hospital emergency department (ED) attendance for accidental overdose,
and mental health events following implant. The aim of this study is to more rigorously assess outcomes
associated with implants compared to heroin dependent persons treated by MMT . The DLS collates general
hospital and mental health admissions plus mortality data for individuals. This allows the health of an individual
to be monitored over time. An electronic version of hospital ED data has recently become available. The study
will validate these records by comparing the electronic data against hospital ED records for the implant group. We
will then combine the electronic ED and DLS data. Morbidity & mortality rates for heroin users are significantly
greater than those for the general population. If the preliminary findings are replicated, naltrexone implants may
offer significant benefits over current pharmacotherapies in reducing general & psychiatric morbidity in
dependent heroin users.
Research achievements (from final report):
Backgroud: Methadone maintenance is the best established treatment for heroin dependence. Sustained release
naltrexone has been tested as an alternative treatment in a number of countries. In Australia, it is only available
under "special access scheme" guidelines. The Australian implant is claimed to have therapeutic effects for about
six months but case studies have raised safety concerns about the use of sustained release naltrexone in Australia
and elsewhere. Method: This study used hospital record linkage to assess the major health outcomes for a large
group treated with a new form of sustained release naltrexone in Western Australia in 2001-02. Results: There
were no heroin "overdoses" requiring hospital treatment in the 6 months after treatment, with few in the following
6 months. Comparison with a group treated with methadone showed that the two groups has a similar rate of
mortality in the three years following treatment (methadone 5.83 and naltrexone 3.76 deaths / 1000 person-years.)
Following naltrexone treatment, the rate of hospitalisation with mental health disorders fell for most disorders. For
drug-related disorders, the risk of opioid related disorders fell for the 3.5 years post naltrexone treatment but not
following methadone treatment. However, the naltrexone group had increased risk of non-opioid drug admissions.
Conclusions: Together, these findings refute the suggestion by case studies, that sustained release naltrexone in
general is associated adverse outcomes. However, randomised trials are needed to make direct comparison with
other forms treatment for heroin dependence.
Expected future outcomes:
If registered as a therapeutic product in Australia, sustained release naltrexone should provide an alternative type
of treatment for heroin dependence. However, further direct comparsions with outcomes following buprenorphine
treatment are required.
Name of contact:
Email of contact:
Prof Gary K Hulse
gary.hulse@uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
353590
Prof Sergio E Starkstein
Geriatrics and Gerontology
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2005
2008
$360,973.00
Standard Project Grant
Title of research award: The Diagnosis of Depression in Alzheimer's Disease
Lay Description (from application):
During the next 3 decades the number of persons older than 85 years will more than double, and the health care
need of this burgeoning population are assuming greater importance. Among the most significant but often
overlooked conditions in the elderly is depression, which is associated with marked disability, functional decline,
risk of hospitalization, diminished quality of life, caregiver burden, increased service utilization, and mortality
from comorbid medical conditions or suicide. The World Health Organization predicts that by 2020 depression
will be second only to heart disease as a cause of disability and premature death in established market economies.
Depression is missed in approximately half of all elderly persons with mood disorder, and this frequency is
certainly higher among individuals with dementia. The strategy to diagnose depression in dementia needs to be
revised. Patients' reports are often unreliable due to memory problems and lack of full insight into their mood and
behavioural changes. Caregivers may overestimate patients' symptoms of depression, especially when they
themselves are depressed and overburdened, and clinicians' diagnoses are sometimes based on biased information
and short observation periods. The situation in nursing homes is even worse, and there is a shortage of studies on
how to diagnose depression in institutionalised patients with dementia. Using specific instruments to assess mood,
behaviour and cognition we will develop valid and reliable criteria to diagnose depression in the different stages
of dementia, and for patients living in different settings. This will facilitate the early recognition and adequate
treatment of depression in individuals with dementia, it will greatly improve patient's quality of life, and will have
a positive impact on caregivers' psychological well-being.
Research achievements (from final report):
Our study demonstrated that about half of the patients with Alzheimer's disease (AD) will suffer from depression
at some stage of the disease. Major depression was the most common type of affective disorder in our sample. We
also found that depression in AD is not a fleeting phenomenon, but may last for about 12 months. Furthermore,
34% of AD patients without depression at baseline developed depression during a 12-month follow-up period. We
found that many patients with depression were not treated for their mood disorder, but we also found a high
proportion of AD patients on antidepressants who continued to be depressed, suggesting that the treatment had
poor efficacy. Another important finding was that loss of interest, loss of pleasure, feelings of guilt, suicide
ideation, psychomotor slowness, agitation, anxiety, loss of energy, nihilistic ideas, and oversleeping were all
significantly associated with sad mood. Therefore, these symptoms should be used to diagnose depression in AD
patients with mild and moderate dementia. Among patients with severe dementia and difficult communication,
poor appetite was the symptom most strongly associated with sad mood. One limitation to the diagnosis of
depression in dementia is that patient may not be fully aware of the extent of their depressive symptoms. In
support, we found that AD patients significantly minimized their depressive symptoms, as compared with reports
provided by their respective caregivers. Finally, we also found that depression in AD patients partially accounted
for the severity of depression among caregivers, suggesting that the successful treatment of depression in dementia
may improve the psychological well-being of caregivers.
Expected future outcomes:
We empirically valididate specific criteria to diagnose depression in AD. This will help to identify more
homogeneous groups of patients who may benefit from specific therapeutic intervention. We plan to explore the
efficacy of pharmacological and psychological treatments of depression in AD.
Name of contact:
Email of contact:
Sergio E Starkstein
ses@meddent.uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
403909
Dr David B. Preen
Epidemiology
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$133,750.00
Standard Project Grant
Title of research award: Morbidity, mortality and health services use among criminal offenders: a Western
Australian population-based study
Lay Description (from application):
This study will focus on the health of criminal offenders, as a most likely marginalised and neglected section of
the community, in order to identify areas of need that if addressed will possess benefits for both offenders and the
general community. A research team will apply their public health, criminology and forensic psychology
expertise, in partnership with the WA Police Service, to provide information on the health outcomes and health
service use of adult offenders in WA. Four themes will be explored: (1) Health Status, to estimate the prevalence
of overall and cause-specific hospital-treated morbidity (2) Mortality, to estimate the prevalence of overall and
cause-specific mortality, (3) Health Service Use, focussing on both the rate of primary and secondary health
service use; and (4) Inequalities In Health Outcomes, firstly comparing the health outcomes of adult offenders
with the general WA population, and secondly, comparing the health outcomes of adult offenders based on
sanction severity and custodial setting. This investigation is one of only a few worldwide to study health among
criminal offenders. Offenders are a neglected section of the Australian health system. Responding to their needs is
not possible without an understanding of their health outcomes and the disparities that exist. An important public
health opportunity therefore exists to investigate the health of this socially disadvantaged group. This study will
provide more detailed data regarding offender-health than currently exists internationally or nationally. Results
can be used by health and/or justice administrators as indicators of program and service performance, and
potentially lead to improved collaboration between these sectors. The methods used for outcome evaluation can be
used readily for the routine evaluation of health performance indicators for offenders.
Research achievements (from final report):
This study used cross-jurisdictional/discipline data linkage to examine the health of adult offenders to identify
areas of health need, that if addressed would benefit both offenders and the wider population. In summary, the
significant research outcomes of this project were as follows: 1. Aided in the establishment of routine linkage of
data between the WA Departments of Health and Corrective Services. This linkage (not available elsewhere in
Australia) will facilitate future research to examine critical issues regarding offender-health and implications for
the wider health system. 2. Development of research/statistical methodology for analysing cross-jurisdictional
linked data, which will aid future research in this area. 3. Results identified vulnerable offender sub-populations in
terms of morbidity and mortality based on sanction severity, recidivism and Aboriginality. 4. Findings
demonstrated inequity between metropolitan and country-based offenders in terms of health service provision and
risk of hospitalisation and death. 5. Results of work investigating the number and cost of hospital stays in the first
12 months post-prison release found that >20% of offenders are admitted to hospital with preventable conditions
resulting in substantial health care costs. o A briefing paper is being prepared to be sent to the Department of
Corrective Services to inform policy relating to monitoring high risk offenders after prison release. 6. Output from
this project acted as preliminary work for further successful nationally-competitive research grants including a
multi-institutional NHMRC project grant. 7. This project resulted in the commencement of a separately-funded
PhD investigating the prevention and treatment of psychiatric illness in offenders.
Expected future outcomes:
Three journal articles are currently under review and are expected to be published by mid-to-late 2009. This
research has laid the foundation for two other successful nationally-competitive research grants to further explore
the major health issues/inequities for the marginalised offender population. It has led to a recently-commenced
PhD to investigate mental health in the offender population.
Name of contact:
Email of contact:
A/Prof David Preen
david.preen@uwa.edu.au
NHMRC Research Achievements - SUMMARY
Grant ID:
CIA Name:
Main RFCD:
Admin Inst:
403994
A/Pr Mathew T. Martin-Iverson
Central Nervous System
University of Western Australia
Start Year:
End Year:
Total funding:
Grant Type:
2006
2008
$247,500.00
Standard Project Grant
Title of research award: Standardisation of prepulse inhibition of the startle reflex for pharmacological and
interspecies comparisons
Lay Description (from application):
People and other animals startle when they here a sudden loud sound. How much one startles depends in part on
how loud the sound is. The relationship between the loudness of the sound and the size of the startle resembles a
ski slope. Each individual has a ski slope that differs from others; the beginning of the ski slope (threshold) occurs
at a different loudness, the slope is a different steepness, and the height of the ski slope where the plateau occurs is
different. There are genetic differences in ski slopes as well. The size of the startle reflex can also be reduced by
preceding the startling sound with a quiet stimulus a few tens of milliseconds before the startling stimulus. This is
known as "prepulse inhibition of the startle reflex" or PPI for short. There is much interest in PPI, because it
differs in people with certain mental illnesses, such as schizophrenia or post-traumatic stress disorder, and certain
neurological illnesses, such as Huntington's chorea. It is also affected by drugs, including stimulants, stress
hormones, and cannabis. In almost all the hundreds of experiments on PPI the effect of the prepulse on the
response to a startling stimulus is measured at only one startling stimulus loudness. This loudness can be at very
different parts of the ski slope for different people or other animals: it may be in the steep slope for one person,
well into the plateau for another, or even at the bottom of the ski slope below the threshold in others. The effect of
PPI is very different depending on what part of the ski slope the loudness represents. A lack of consistent effects
in the literature on PPI by drugs and genetics is explained by this difference. Experiments are planned that will
investigate the effect of drugs that are similar to those that treat schizophrenia, stress hormones and cannabis on
the effect of prepulses on the whole ski slope. This procedure will provide the consistency in results so far absent.
Research achievements (from final report):
In relation to the aim of establishing cross-species standardisation of measurement of prepulse inhibition of the
startle reflex (PPI), the effect of manipulating prepulse and pulse stimuli intensities were investigated in mice, rats
and humans. Using this method, developed and improved over several years, novel insights into the basic neural
dysfunction in schizophrenia were discovered, first in animal models, including genetic models in mice and
pharmacological models in rats, and then extended to clinical research in people suffering from Schizophrenia,
and people that abuse cannabis regularly. Interestingly, we found that cannabinoid agonists produce effects in rats
similar to those observed in people who use cannabis, and these are similar to effects observed in patients with
Schizophrenia. It was also discovered that the level of stress hormones alters the effects of cannabis-like drugs in
this model, with schizophrenic-like effects depending on the level of stress hormone. This opens a new area of
stress-cannabis interactions for future study. In addition, the method was used to assess the psychotomimetic
effects of novel analogues of MDMA ("Ecstasy"), developed for the treatment of Parkinson's disease, leading to
new potential treatments that are positive in primate models and are now under further development. As a
consequence of results investigating the relationship between hypothermic effects of dopamine agonists and their
PPI effects, we discovered a possible genetic model for neuroleptic malignant syndrome, a life-threatening
disorder that afflicts some people treated with antipsychotic drugs.
Expected future outcomes:
This research furthers knowledge of schizophrenia, its relationship to cannabis use, and the causes of
schizophrenia. The methods will also be of use in assessing the risk of psychosis and attentional deficits of new
treatments for Parkinson's disease and current drug treatments for Attention Deficit Disorder, such as
amphetamine.
Name of contact:
Email of contact:
Mathew Martin-Iverson
mathew.martin-iverson@uwa.edu.au