Health and Autism
Needs, Rights, Responsibilities and Widening Perspectives
24th November 2005
Conference Report
1
CONTENTS
Introduction
Page 3
Programme
Page 4
Minister’s Speech
Page 5
Presentations
Page 8
Workshops
Page 12
2
INTRODUCTION
The National Conference on Health and Autism held in Aviemore on 24th November 2005
aimed to widen the dialogue about health needs in autism in Scotland and to focus on
contributing to a broader perspective on how we deliver interventions. In total 190 delegates
attended the event including 25 parents and carers of people with ASD.
The Public Health Institute of Scotland (PHIS) report on the needs of those with autism
spectrum disorders, commissioned by Scottish Ministers, highlighted the need to disseminate
research findings to health and social care professionals so that they could consider and apply
these in their own localities where they thought it appropriate to do so. The Scottish
Executive hosted this conference as part of the implementation of this recommendation.
In the Deputy Minister for Health and Community Care’s welcome speech, he highlighted the
responsibility we all have to address the individual needs and rights of people with autism
spectrum disorders in relation to health, education and social care. This conference focussed
on health and provided an opportunity for health and social care professionals, parents and
carers and people with autism spectrum disorders (ASD) to hear the most up to date
perspectives on autism health needs and look at where research needs to focus in the future.
The Executive’s ASD Reference Group formed a small planning group of experts who
selected an appropriate programme for the day. Experts in the field of ASD were invited to
present current research addressing the health needs of people with ASD. The programme
included psycho-social interventions and the development of cognitive behaviour therapy;
dietary interventions; pharmacological treatments; genetic counselling; improved assessment
and diagnosis and the individualised treatment of medical disorders often associated with
autism. The prominent immunologist who was invited to speak had to withdraw at short
notice. To address this gap, sources of information on immunology have been included in
this report in Annex A. Presentations from Tom Jennings, Moira Dickinson and Jane Hook
provided delegates with the important perspective of what it means for people and their
families to live with ASD.
The conference placed a strong emphasis on the importance of primary health care
professionals in effectively treating the wide range of health needs of people with ASD and
identifying and treating the comorbid conditions often associated with ASD. The conference
report will be disseminated widely to reach health professionals who were unable to attend
the conference.
3
PROGRAMME
9:30
Chairman’s Introduction and Welcome
Ms Jean MacLellan, Scottish Executive Health Department
9:35
Overview of Policy
Mr Lewis Macdonald, Deputy Minister for Health and Community Care.
9:45
Asperger’s Syndrome – Unrecognised, Understood & Beyond
Tom Jennings
10:00
Carer’s views on meeting health needs
Jane Hook MBE & Moira Dickinson
11:00
Biomedical perspectives on autism spectrum disorder: current knowledge
and new perspectives
Professor Chris Gillberg MD, PhD
12:00
Future Research Agenda – what is needed?
Dr Justin Williams
12:30
Lunch
13:30
PARALLEL SESSION A
1.
Immunology (workshop withdrawn)
2.
Dietary issues
Dave Rex, Child Health Lead Dietician, NHS Highland and Gordon Bell,
University of Stirling
3.
Mental Health: Imaging the developmental neurobiology of ASD
Dr Stephen Lawrie, University of Edinburgh
The contribution of Neuropyschology to our understanding
and management of ASD
Mr Robert Walley, Consultant Clinical Psychologist, NHS Lothian
4.
Psycho-social interventions
Dr Ken Aitken, Clinical Psychologist, GGPHCT (Session A)
Dr Tommy MacKay, Consultant Psychologist and Dr Anne Greig,
Psychologist, Argyll and Bute Council (Session B)
5.
Genetics and ASD
Dr Birgitta Bernhard, SpR in Clinical Genetics, Western General
Hospital
Professor Anthony Monaco, Director and Head of Neuro-genetics Group, The
Wellcome Trust Centre for Human Genetics.
6.
Medication Issues
Dr Anne Gilchrist, Consultant in Adolescent Psychiatry, NHS Grampian Trust
Craig Melville, Senior Lecturer, University of Glasgow
15:00
PARALLEL SESSION B - Repeated as per Session A
4
SPEECH BY DEPUTY MINISTER FOR HEALTH AND COMMUNITY CARE,
LEWIS MACDONALD
Health and Autism – Needs, Rights, Responsibilities And Widening Perspectives
Conference
Although I unfortunately cannot be with you today I would like to welcome all of you to this
important conference. As the programme states, it aims to give us all the opportunity to think
about needs, rights, and responsibilities.
And whilst we all have responsibilities in making sure we do better for people with autism
spectrum disorder, it is primarily their individual needs and rights that we want to address.
So what are the needs of people with ASD? To help us identify what we needed to do
nationally, the Executive commissioned the Public Health Institute of Scotland to conduct an
ASD Needs Assessment some 4 years ago.
That report identified a lack of services and supports for people with ASD in Scotland. It set
out a clear need for people to have quicker access to diagnosis and assessment and to have
better information about ASD. Most importantly, people with ASD need an appropriate
response from health, education and social care services. Today our focus is on health.
Our work to date has included a number of training initiatives that will ensure primary care
and social care staff have a better understanding of autism spectrum disorders.
We have also issued a quality standard for diagnostic services that identify what individuals
and families can expect from services. A number of diagnosis training pilots are also
underway with a view to broadening the range of professionals who can offer this service.
The outcome should be to provide quicker access to diagnosis and to more specialist services
when these are needed.
I said that people diagnosed with ASD need a response from services. In the past,
particularly for adults, there has been little to meet their needs. The Autism Resource Centre
in Glasgow and Number 6 in Edinburgh are both projects that are demonstrating how
partnerships can deliver services that give adults with ASD – and their family carers – a
better quality of life.
For all of us, our quality of life is dictated by how healthy we are. People with ASD are no
different. They too are people who need to visit GPs dentists and general health services for
the same things as everyone else. However, it is recognised that some are also more
vulnerable to other illnesses.
Having a diagnosis of ASD does not mean that problems with physical or mental health are
necessarily part of the condition. These problems need to be addressed and treated where
appropriate.
However, I am sure you will get a much clearer message from Tom Jennings, Jane Hook and
Moira Dickinson about what having an autism spectrum disorder means to people and their
families. They know best what their needs are, and can tell us how we can better meet those
needs.
5
I am well aware that the majority of support for children and adults with ASD comes from
family carers. They too have needs and rights that include their own health and well-being.
The Needs Assessment described the impact on family members of caring for a child or adult
with autism.
Part of the stress experienced by families is caused by a lack of services, support and
information.
On the information front, the Executive is funding 2 projects that will provide families with a
range of essential information about autism, and direct them to where they can get support.
Getting this information at the point of diagnosis will hopefully alleviate some of the stress
caused by fear and uncertainty.
The Needs Assessment identified the uncertainties about what interventions work for children
and adults. I expect most of you here today will be aware of the draft guideline that is being
developed by the SIGN Council.
Looking at assessment, diagnosis and clinical interventions for children and young people
with autism spectrum disorders, the SIGN Council and development group are conducting a
systematic review of evidence.
The SIGN process necessarily uses strict criteria to categorise levels of research evidence to
inform recommendations for clinical practice. These rules apply to all guidelines. There are
clearly gaps in research into effective interventions for people with autism. The SIGN
Guideline and other work will help identify what research is needed.
I know parents will be confused by information about treatments that are not available in
Scotland. I am also well aware that some believe we have a closed mind to practice in other
parts of the world.
I cannot advocate interventions where there may still be concerns about potential adverse
effects. What I can do is to encourage professionals to have an open mind to developing
interventions.
And we in the Scottish Executive can help to ensure that information about developments is
as widely available as possible. That is what today is about.
I know some people disagree with our approach to autism. Why are we in the Executive
following the recommendations of the Needs Assessment? Why are we working to improve
life-long services? Some families will be asking why we are not tackling the cause rather
than the effect of autism.
Again, I have to take forward policy that is based on the best available scientific evidence.
On that basis we have to do more to provide services and support for people with ASD and
their families throughout their lives. That is what many families are asking us for.
I am very grateful to members of our national reference group and related sub groups who
have given enormous energy and commitment to our common goal of giving people with
ASD a better quality of life.
6
Our future work will move on from diagnosis and training to making sure policy turns into
practice. We want to support families to build their capacity to support their sons and
daughters. We want to make sure general and specialist services are able to recognise and
meet the needs of people with ASD.
And we want to do this with an open mind. Today we want people to have clearer
information about successful and developing interventions that improve the health and
wellbeing of children and adults with autism spectrum disorders.
I would also like to acknowledge the contribution of the Cross Party Group on Autism in
identifying key issues for today’s programme.
I am delighted that so many people with a wealth of knowledge have come here today to
share that with you. I am sure many of our delegates will go away with new perspectives on
diet and psycho-social interventions, on mental health, genetics and medication.
Professor Gillberg and Dr Williams will no doubt provide everyone with the most up to date
perspective on autism and a clear steer about where our research needs to focus in future.
Thank you all for your contribution and for your participation. I hope we can continue to
work together to bring about the changes that individuals and families need.
7
PRESENTATIONS
Asperger’s Syndrome – Unrecognised, Understood and Beyond
Tom Jennings
Tom Jennings was diagnosed with Asperger’s Syndrome in 2003 at the age of 33. Since then
he has been regaining lost abilities after struggling with life for many years. An
understanding of Asperger’s has unlocked many of his problems and life is making sense,
with great relief.
Tom gave an overview of some of the difficulties he has faced. He shared his feelings and
experiences, prior to diagnosis and following diagnosis and recognition of his condition. He
explained the feelings of fear, pain, confusion and despair he experienced growing up with
Asperger’s and not understanding why he felt the way he did.
The diagnosis he received in 2003 was a big relief. He felt he had been ill for 30 years and
was shocked and dumbfounded. He was able to start dealing with the implications of his
diagnosis and accessing the help that he needed. Tom is now keen to tell people in education
the importance of having understanding and respect for those on the autism spectrum.
8
Carer’s Views on Meeting Health Needs
Jane Hook MBE
Jane is the mother of Rachel, now 19, who has autism. After a traumatic experience in
fighting for diagnosis and support, she felt compelled to fight and help other families gain
diagnosis and assessment, appropriate education and family support.
Jane addressed the difficulties experienced by children and adults with ASD in accessing
mainstream health services. She described the problems she faces when taking her daughter
to the dentist to illustrate the need for professionals to be trained adequately to treat people
with ASD.
Jane highlighted the importance of professionals in primary care providing effective and
appropriate care to the range of health needs of people with autism spectrum disorders.
Moira Dickinson
Moira has two daughters, Sarah age 20 who was diagnosed at 3 1/2 with high functioning
autism and Joanna aged 14. Moira explained that having to fight for Sarah to get her needs
met has had an impact on all the family. They really saw progress in addressing Sarah’s
needs when she started a unit specifically for high function autism/ Aspergers at a High
School.
Moira talked about a Communication Passport Sarah carries, which outlines her skills and
also describes some of the communication problems people may experience in dealing with
Sarah.
Moira described her daughter Sarah’s experience at a further education college, where she
was supported with a class teacher and speech therapist before starting a 2 year course, but
she had been unable to complete the second year due to too much change and unsupported
activities. Moira’s talk focussed on the need for support in colleges and special courses
aimed at people with ASD. She also highlighted the need for support for siblings of people
with ASD.
Moira explained that there is help out there to support people with autism and their families
but many are still unable to access it. We now need to focus on making support accessible.
9
Bio-medical perspectives on autism spectrum disorder: current knowledge and new
perspectives
Christopher Gillberg MD PhD
Professor of Child and Adolescent Psychiatry.
Professor Gillberg is one of the leading international researchers on autism spectrum
disorders and other neuropsychiatric disorders with early childhood onset. Professor Gillberg
is also a clinician with more than 30 years of experience in psychiatry and child neurology.
Key Messages
Autism is a behavioural syndrome comprising restricted two-way social interaction, restricted
verbal and non-verbal communication and restricted imagination/behavioural repertoire. It
comes in several different clinical variants including autistic disorder and Asperger’s
syndrome, and with or without major comorbidities (mental retardation, epilepsy,
chromosomal, and other medical disorders). Reference is now often made to autism spectrum
disorders, a term covering both the classic Kanner syndrome of autism and the variants
described by Asperger and Heller plus a number of other autistic-like conditions. A number
of behavioural problems commonly occur in autism. These include attention deficits,
hyperactivity, obsessions and compulsions, depression, anxiety, tics and violent behaviours.
Autism is one of the most strongly genetic conditions in child neurology/psychiatry.
However, it can also be primarily associated with major brain damage caused by a number of
well-established medical conditions, such as PKU, rubella embryopathy, herpes encephalitis,
tuberous sclerosis and a number of chromosomal disorders, including the fragile X syndrome.
Autism spectrum disorders occur in more that 0.5% of the general population of children,
whereas the classic condition that Kanner described is probably at a rate of 0.1-0.2%. There is
no good evidence that the prevalence of autism has actually increased, but the diagnostic
boundaries have been broadened and awareness has increased dramatically over the past
twenty years, leading to more cases being detected and correctly diagnosed.
Educational and behavioural interventions can lead to lasting improvements. Medical
therapies can sometimes be helpful. Genetic and clinical research as well as basic
neurobiological studies will help throw considerably more light on the various syndromes in
the autism spectrum during the next five to ten years. At the present stage of our knowledge,
autism spectrum disorders usually lead to life-long disability to one degree or another even
though variability in terms of outcome is very considerable.
10
Future Research Agenda – What is Needed?
Dr Justin Williams
Senior Lecturer and Hon. Consultant in Child Psychiatry, University of Aberdeen and Royal
Aberdeen Children’s Hospital
Key Messages
We have now reached a stage where Autism is a well-defined condition, awareness is high
and excellent diagnostic methods are available. Now we need to develop effective
psychological and biological treatments. Even though autism is inherited many
environmental factors may affect the outcome. For example the treatment of comorbid
conditions which may have very severe consequences in themselves, therapeutic
interventions or the social environment. Comorbidity is common and not an exception and all
challenging behaviour should not be assumed to be simply arising from untreatable autism.
Better assessment and treatment of comorbidity is required.
The issue of brain growth rates was considered. Brain images of people with autism show
the grey matter in the brain is increased and white matter decreased. This would indicate
there is poor long-range connectivity and greater local connectivity. Psychological processes
dependent on long range activity include imitation and joint attention. Impairments in white
and grey matter development affect these functions developing. Impaired connectivity
between frontal and dorsal systems may lead to poor joint attentions, rigid inflexible
behaviour and frontal immaturity.
A number of potential targets for research to improve therapies were outlined including:
white and grey matter development; attentional regulation and the development of motor
skills in autism; mechanisms of anxiety; and interventions that promote imitation and joint
attention skills.
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WORKSHOPS
Workshop 1. Immunology
This workshop was withdrawn as the speaker was unable to attend. A list of peer reviewed
publications on immunology and autism can be found in Annex A.
Workshop 2. Dietary Issues
Diet and ASD – How Do They Affect Each Other?
Dave Rex, Child Health Lead Dietician, NHS Highland
Key Messages
Most children with ASD have diets that are particularly (self) restricted which can affect
behaviour due to a variety of reasons which may include blood sugar fluctuations, lack of
iron and zinc, and lack of vitamins. There may well be sub-groups within the ASD
population with shared biochemical and physiological problems, who would be more likely
to respond to a particular dietary intervention. Dieticians need to develop a supporting role,
helping to navigate families safely through the considerable “trial and error” of diet therapy
in ASD. Scientific evidence may be weak, but there is little conclusive evidence against these
interventions either. The best known and least controversial interventions were covered by
the workshop.
Gluten and Casein Free Diets There is insufficient evidence for this to become the standard
treatment for all people with ASD. However, there is enough evidence to warrant a
supervised trial in some cases. Casein free trials take 6 weeks, and gluten free trials take 6
months before conclusions can be drawn. If no benefits are seen, the substance should be reintroduced. Both diets can be difficult to follow, particularly for people with ASD as so many
of them are already highly selective in their food choices. Appropriate dietary supervision
helps to ensure that important nutrients are replaced with other food sources or supplements.
There is evidence however that the nutrition status of children with ASD on GF / CF diets is
no worse than those children with ASD who are not on the diet.
Fish oil supplements are widely used by families affected by ASD. Anecdotal accounts of
positive impact are common place. There is also a published case study describing the
positive impact of fish oil on a patient with ASD. However, there have been no placebo
controlled studies using fish oil supplements for ASD. Some fairly well designed studies do
suggest a positive effect in other neuro-developmental disorders and mood disorders. Because
fish oil takes time to build up in the fatty tissue it is sensible to give any trial a while to take
effect. If no improvements are seen after 3 months (the length of most research trials), it
should be stopped. EPA in fish oil may be more important than DHA.
12
Table Summarising Diet Therapy in ASD
Intervention
Difficulty
Evidence
Efficacy
Fish
oil Low
supplements
Gluten
and High
casein free diet
Low
Removal
of Low
“excitotoxin”
food additives
Moderate
Low
vitamin
/
mineral
supplement
Phenol / amine Moderate
restriction
Low
Moderate
of Negative
Comments
impact on
nutrition
None
Moderate
evidence
for
typically co-morbid conditions.
Possible
Consider
impact
on
magnesium, calcium, protein
and fibre intake
None
ASD specific evidence is
lacking, but it is easy to do.
Moderate
None
Useful for selective eaters.
May help parents and carers
relax at mealtimes.
Low
Possible
Fruit & veg have positive
antioxidant role which may be
particularly important in ASD
Essential Fatty Acid (Efa) Deficiency in Autism and Related Neurodevelopmental
Disorders
Gordon Bell, Nutrition Group, Institute of Aquaculture, University of Stirling.
Key Messages
Fatty acid deficiency may cause autoimmune problems, GI/urinary problems, sleep problems,
mood disorders, behavioural problems and perceptual and cognitive difficulties. There is
evidence that EPA and GLA supplementation may help improve the general health, sleep
pattern, cognitive skills, concentration and sociability of children with ASD However some
parents have also reported improved cognitive skills but increased hyperactivity and
behavioural problems following increased fish oil intake. This can sometimes be reversed by
pre-loading with GLA or increasing GLA intake while maintaining the EPA dose.
More research is needed on diet therapy and ASD. Dr Bell has received funding from the
Chief Scientist’s office for a 2 year study of “Blood fatty acid and phospholipase A2 as
indicators of abnormal phospholipid metabolism in autism: The potential for intervention
using fatty acid supplements”.
13
Workshop 3. Mental Health
Imaging the Developmental neurobiology of ASD
Dr Stephen Lawrie
Reader in Psychiatry, University of Edinburgh
Brain imaging in ASD can screen for structural brain lesions (sMRI) and diagnose epilepsy
(EEG). With ongoing research and a refined understanding it also has the potential to aid in
the identification of risk genes and their phenotypic expression. Imaging (and/or genetics)
could also aid in early diagnosis, prognostic and treatment planning, and even in developing
new treatments.
There are key problems in conducting reliable and valid brain imaging studies of ASD
including the impossibility of finding an appropriate control group and capturing the
developmental path. The key findings concerning brain structure (including from systematic
reviews and meta-analyses) can be influenced by the choice of different control groups.
Structural and functional imaging studies in ASD have begun to identify consistent global
and regional brain differences compared to healthy controls. These can be linked to early
genetic effects and (social and motor) aspects of the typical features of ASD.
The Contribution of Neuropsychology to our Understanding and Clinical Management
of Autistic Spectrum Disorders
Mr Robert Walley
Consultant Clinical Psychologist, Primary Care Division – NHS Lothian
Mr Walley was unable to present at the conference. The following is the synopsis he
provided beforehand.
The presentation will include a brief introduction to the study of neuropsychology. It will
then review the major psychological theories/models that have been helpful in our
understanding of autistic spectrum disorders and discuss their general utility in relation to
clinical management. The neuropsychological aspects of these theories will then be discussed
with particular reference to the “ Theory of Mind “ and Executive Dysfunction models. The
presentation will conclude by discussing how our improved understanding of the
neuropsychology of autistic spectrum disorders may help in its management.
14
Workshop 4: Psycho-social Interventions
Ken Aitken
Clinical Psychologist, GGPHCT
Tommy MacKay & Dr Anne Greig
Consultant Psychologist, Psychology Consultancy Services and National Centre for Autism
Studies, University of Strathclyde
A wide range of psycho-social interventions have been used with autism spectrum disorders.
These include very diverse approaches such as applied behavioural analysis (ABA), Option
and social interaction training.
This workshop provided an overview of this field and of the status of a variety of
interventions in terms of their evidence base. The presenters talked about aspects of their
own current work and interests in this area, including the developing field of cognitive
behaviour therapy (CBT) and its application to autism.
Ken Aitken reported on the regional variations in reported prevalence of ASD in Scotland.
He also outlined the features that he recommended should lead to early investigations for
ASD including: no babbling by 12 months; no pointing or other gesturing by 12 months; no
single words by 16 months; no 2-word spontaneous phrases (not echolalic) by 24 months; or
any loss of any language or social skills at any age. He detailed the history of psychosocial
interventions with ASD and focused on commonalities across clinical subgroups of ASD.
A number of limitations were discussed in giving general statements about treatment
approaches which are effective with ASD. Firstly there is a wide span of cognitive and
verbal abilities in those with ASD - it is important to ensure that the published literature in on
use of the technique with a comparable population. Also there are difficulties in ensuring
“treatment fidelity” - there are now a number of studies on the differences found between
early intervention programmes, comparing parent and professionally led interventions.
15
Workshop 5: Genetics and ASD
Dr Birgitta Bernhard
Specialist Registrar Clinical Genetics
South East of Scotland Clinical Genetics Services, Western General Hospital
Identifiable syndromes and chromosome abnormalities account for a small percentage of
ASDs. It should not be assumed that an apparent lack of dysmorphism prevents the need for
molecular and cytogenetic testing. Shared symptoms may result from the disruption of gene
or protein systems that may also be disrupted in the complex genetic syndrome of ASD.
Genetic counselling remains challenging given the complexity of the phenotype and the
underlying aetiology. The presentation reviewed current approaches and discussed the role of
the clinical geneticist.
Professor Tony Monaco
Director and Head of Neuro-genetics Group
The Wellcome Trust Centre for Human Genetics
Rapid progress has been made in the molecular understanding of single gene disorders during
the last 15 years. A new challenge in human genetics is to unravel the genetics of more
complex, polygenic diseases, which are relatively frequent in the population. Using
resources provided by the human genome project and advances in genotyping technology and
statistical genetics, research groups at the Wellcome Trust Centre for Human genetics are
searching for susceptibility genes underlying polygenic disorders.
Professor Monaco explained his laboratory have initiated genetic studies of complex
neurodevelopmental disorders of childhood, including autism. As part of the International
Molecular Genetic Study of Autism Consortium (IMGSAC), his team have completed a full
genome scan for susceptibility genes in autism and found strong evidence for linkage to
chromosomes 2q, 7q and 16p1-4. These chromosome regions implicated by family studies in
autism have been replicated in independent families. The regions containing the
susceptibility gene(s) are being further investigated by family based association studies.
Candidate genes in the critical region are tested for etiologic mutations or variants that are
potentially involved in susceptibility to autism. Recently, using a high density screen of
single nucleotide polymorphisms on chromosome 7q and 2q, we have identified strong SNP
associations with autism which now require replication in independent cohorts. Our goal is
for a molecular understanding of the neurodevelopmental pathways involved in autism,
which should enable better diagnosis and potential treatments.
Professor Monaco gave a summary of molecular genetics research into ASD - several groups
have carried out genome screens for linkage to autistic spectrum disorder and there is
encouraging convergent evidence for linkage in some regions. Many candidate screening and
association studies have been carried out, but no etiological variants have been so far
conclusively identified in the majority of families with autism. Several positive risk
haplotypes have been identified on chromosome 7q and 2q that need to be replicated.
16
Workshop 6. Medication Issues
Dr Anne Gilchrist
Consultant in Adolescent Psychiatry, NHS Grampian Trust
Dr Craig Melville
Senior Lecturer, University of Glasgow
Estimates of the proportion of individuals with autism spectrum disorders receiving
psychotropic medication vary from 20% to over 70%, depending on the sample of individuals
studied. Use of medication has implications for individuals, their families, and for
professionals in a wide range of agencies, including educational and social care as well as
health services.
Medication may be prescribed for several reasons, including treatment of a diagnosed
condition, such as depression; attempted treatment of the core features of autism spectrum
disorders; or for the management of problem behaviours, such as aggression. This workshop
explored the principles, evidence base and practical use of psychotropic medication when
working with individuals of any age with autism spectrum disorders.
17
ANNEX A
BASIC PEER REVIEWED PUBLICATIONS ON IMMUNOLOGY AND AUTISM
Connolly AM, Chez M, Streif EM, Keeling RM, Golumbek PT, Kwon JM, Riviello JJ, Robinson RG,
Neuman RJ & Deuel RM.
Brain-Derived Neurotrophic Factor and Auto antibodies to Neural Antigens in Sera of Children with
Autistic Spectrum Disorders, Landau-Kleffner Syndrome, and Epilepsy.
Biol Psychiatry. 2005 Sep 19; [Epub ahead of print]
PMID: 16181614
Laurence JA & Fatemi SH.
Glial fibrillary acidic protein is elevated in superior frontal, parietal and cerebellar cortices of autistic
subjects.
Cerebellum. 2005;4(3):206-10.
PMID: 16147953
Zimmerman AW, Jyonouchi H, Comi AM, Connors SL, Milstien S, Varsou A & Heyes MP.
Cerebrospinal fluid and serum markers of inflammation in autism.
Pediatr Neurol. 2005 Sep;33(3):195-201.
PMID: 16139734
Sperner-Unterweger B.
Immunological aetiology of major psychiatric disorders: evidence and therapeutic implications.
Drugs. 2005; 65(11):1493-520. Review.
PMID: 16033289
Levy SE & Hyman SL.
Novel treatments for autistic spectrum disorders.
Ment Retard Dev Disabil Res Rev. 2005; 11(2):131-42. Review.
PMID: 15977319
Bazar KA, Yun AJ, Lee PY, Daniel SM & Doux JD.
Obesity and ADHD may represent different manifestations of a common environmental over
sampling syndrome: a model for revealing mechanistic overlap among cognitive, metabolic, and
inflammatory disorders.
Med Hypotheses. 2005 May 16; [Epub ahead of print]
PMID: 15905045
Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC & Keating
MT.
Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.
Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8089-96; discussion 8086-8. Epub 2005 Apr 29.
PMID: 15863612
Libbey JE, Sweeten TL, McMahon WM & Fujinami RS.
Autistic disorder and viral infections.
J Neurovirol. 2005 Feb; 11(1):1-10. Review.
PMID: 15804954
Jyonouchi H, Geng L, Ruby A & Zimmerman-Bier B.
Dysregulated innate immune responses in young children with autism spectrum disorders: their
relationship to gastrointestinal symptoms and dietary intervention.
Neuropsychobiology. 2005; 51(2):77-85.
18
PMID: 15741748
Croen LA, Grether JK, Yoshida CK, Odouli R & Van de Water J.
Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a
case-control study.
Arch Pediatr Adolesc Med. 2005 Feb; 159(2):151-7.
PMID: 15699309
Ashwood P, Anthony A, Torrente F & Wakefield AJ.
Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal
symptoms: mucosal immune activation and reduced counter regulatory interleukin-10.
J Clin Immunol. 2004 Nov; 24(6):664-73.
PMID: 15622451
Kennedy RC, Byers VS & Marchalonis JJ.
Measles virus infection and vaccination: potential role in chronic illness and associated adverse
events.
Crit Rev Immunol. 2004; 24(2):129-56. Review.
PMID: 15581394
Trajkovski V, Ajdinski L & Spiroski M.
Plasma concentration of immunoglobulin classes and subclasses in children with autism in the
Republic of Macedonia: retrospective study.
Croat Med J. 2004 Dec;45(6):746-9.
PMID: 15578810
Ashwood P & Van de Water J.
Is autism an autoimmune disease?
Autoimmun Rev. 2004 Nov; 3(7-8):557-62. Review.
PMID: 15546805
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW & Pardo CA.
Neuroglial activation and neuroinflammation in the brain of patients with autism.
Ann Neurol. 2005 Jan;57(1):67-81. Erratum in: Ann Neurol. 2005 Feb;57(2):304.
PMID: 15546155
Vojdani A, O'Bryan T, Green JA, Mccandless J, Woeller KN, Vojdani E, Nourian AA & Cooper EL.
Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism.
Nutr Neurosci. 2004 Jun; 7(3):151-61.
PMID: 15526989
Yun AJ, Bazar KA & Lee PY.
Pineal attrition, loss of cognitive plasticity, and onset of puberty during the teen years: is it a modern
maladaptation exposed by evolutionary displacement?
Med Hypotheses. 2004; 63(6):939-50.
PMID: 15504560
Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ,
Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC & Keating MT.
Ca (V) 1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and
autism.
Cell. 2004 Oct 1; 119(1):19-31.
PMID: 15454078
Ashwood P &Van de Water J.
19
A review of autism and the immune response.
Clin Dev Immunol. 2004 Jun; 11(2):165-74. Review. No abstract available.
PMID: 15330453
Silva SC, Correia C, Fesel C, Barreto M, Coutinho AM, Marques C, Miguel TS, Ataide A, Bento C,
Borges L, Oliveira G & Vicente AM.
Autoantibody repertoires to brain tissue in autism nuclear families.
J Neuroimmunol. 2004 Jul; 152(1-2):176-82.
PMID: 15223250
Hornig M, Chian D & Lipkin WI.
Neurotoxic effects of postnatal thimerosal are mouse strain dependent.
Mol Psychiatry. 2004 Sep; 9(9):833-45.
PMID: 15184908
Vojdani A, Bazargan M, Vojdani E, Samadi J, Nourian AA, Eghbalieh N & Cooper EL.
Heat shock protein and gliadin peptide promote development of peptidase antibodies in children with
autism and patients with autoimmune disease.
Clin Diagn Lab Immunol. 2004 May; 11(3):515-24.
PMID: 15138176
Sweeten TL, Posey DJ, Shankar S & McDougle CJ.
High nitric oxide production in autistic disorder: a possible role for interferon-gamma.
Biol Psychiatry. 2004 Feb 15; 55(4):434-7.
PMID: 14960298
Vojdani A, Pangborn JB, Vojdani E & Cooper EL.
Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes
are major instigators of autoimmunity in autism.
Int J Immunopathol Pharmacol. 2003 Sep-Dec; 16(3):189-99.
PMID: 14611720
Sweeten TL, Bowyer SL, Posey DJ, Halberstadt GM & McDougle CJ.
Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders.
Paediatrics. 2003 Nov; 112(5):e420.
PMID: 14595086
Kurup RK & Kurup PA.
A hypothalamic digoxin-mediated model for autism.
Int J Neurosci. 2003 Nov; 113(11):1537-59.
PMID: 14585753
Ferrante P, Saresella M, Guerini FR, Marzorati M, Musetti MC & Cazzullo AG.
Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children.
Biomed Pharmacother. 2003 Oct;57(8):372-4.
PMID: 14568232
Lipkin WI & Hornig M.
Microbiology and immunology of autism spectrum disorders.
Novartis Found Symp. 2003; 251:129-43; discussion 144-8, 281-97.
PMID: 14521191
Torres AR.
Is fever suppression involved in the etiology of autism and neurodevelopmental disorders?
BMC Pediatr. 2003 Sep 2; 3:9. Epub 2003 Sep 2. Review.
20
PMID: 12952554
Oh HM, Oh JM, Choi SC, Kim SW, Han WC, Kim TH, Park DS & Jun CD.
An efficient method for the rapid establishment of Epstein-Barr virus immortalization of human B
lymphocytes.
Cell Prolif. 2003 Aug; 36(4):191-7.
PMID: 12950388
Sweeten TL, Posey DJ & McDougle CJ.
High blood monocyte counts and neopterin levels in children with autistic disorder.
Am J Psychiatry. 2003 Sep; 160(9):1691-3.
PMID: 12944347
DeFelice ML, Ruchelli ED, Markowitz JE, Strogatz M, Reddy KP, Kadivar K, Mulberg AE & Brown
KA.
Intestinal cytokines in children with pervasive developmental disorders.
Am J Gastroenterol. 2003 Aug; 98(8):1777-82.
PMID: 12907332
Padhye U.
Excess dietary iron is the root cause for increase in childhood autism and allergies.
Med Hypotheses. 2003 Aug; 61(2):220-2. Review.
PMID: 12888307
Singh VK & Jensen RL.
Elevated levels of measles antibodies in children with autism.
Pediatr Neurol. 2003 Apr; 28(4):292-4.
PMID: 12849883
Lee DA, Lopez-Alberola R & Bhattacharjee M.
Childhood autism: a circuit syndrome?
Neurologist. 2003 Mar; 9(2):99-109. Review.
PMID: 12808372
Mari M, Castiello U, Marks D, Marraffa C & Prior M.
The reach-to-grasp movement in children with autism spectrum disorder.
Philos Trans R Soc Lond B Biol Sci. 2003 Feb 28; 358(1430):393-403. Review.
PMID: 12639336
Zoroglu SS, Yurekli M, Meram I, Sogut S, Tutkun H, Yetkin O, Sivasli E, Savas HA, Yanik M,
Herken H & Akyol O.
Pathophysiological role of nitric oxide and adrenomedullin in autism.
Cell Biochem Funct. 2003 Mar; 21(1):55-60.
PMID: 12579522
Shi L, Fatemi SH, Sidwell RW & Patterson PH.
Maternal influenza infection causes marked behavioural and pharmacological changes in the
offspring.
J Neurosci. 2003 Jan 1; 23(1):297-302.
PMID: 12514227
Kidd PM.
Autism, an extreme challenge to integrative medicine. Part 2: medical management.
Altern Med Rev. 2002 Dec; 7(6):472-99. Review.
PMID: 12495373
21
Croonenberghs J, Wauters A, Devreese K, Verkerk R, Scharpe S, Bosmans E, Egyed B, Deboutte D
& Maes M.
Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism.
Psychol Med. 2002 Nov; 32(8):1457-63.
PMID: 12455944
Jyonouchi H, Sun S & Itokazu N.
Innate immunity associated with inflammatory responses and cytokine production against common
dietary proteins in patients with autism spectrum disorder.
Neuropsychobiology. 2002; 46(2):76-84.
PMID: 12378124
Wank R.
Schizophrenia and other mental disorders require long-term adoptive immunotherapy.
Med Hypotheses. 2002 Aug; 59(2):154-8.
PMID: 12208201
Krause I, He XS, Gershwin ME & Shoenfeld Y.
Brief report: immune factors in autism: a critical review.
J Autism Dev Disord. 2002 Aug; 32(4):337-45. Review.
PMID: 12199139
Kidd PM.
Autism, an extreme challenge to integrative medicine. Part: 1: The knowledge base.
Altern Med Rev. 2002 Aug; 7(4):292-316. Review.
PMID: 12197782
Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K & Vojdani E.
Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with
encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A.
J Neuroimmunol. 2002 Aug;129(1-2):168-77. Erratum in: J Neuroimmunol 2002 Sep;130(1-2):248.
PMID: 12161033
Wakefield AJ.
Enterocolitis, autism and measles virus.
Mol Psychiatry. 2002; 7 Suppl 2:S44-6. Review. No abstract available.
PMID: 12142948
Wakefield AJ, Puleston JM, Montgomery SM, Anthony A, O'Leary JJ & Murch SH.
Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands.
Aliment Pharmacol Ther. 2002 Apr; 16(4):663-74. Review.
PMID: 11929383
Korvatska E, Van de Water J, Anders TF & Gershwin ME.
Genetic and immunologic considerations in autism.
Neurobiol Dis. 2002 Mar; 9(2):107-25. Review. Erratum in: Neurobiol Dis 2002 Jun; 10(1):69.
PMID: 11895365
Patterson PH.
Maternal infection: window on neuroimmune interactions in foetal brain development and mental
illness.
Curr Opin Neurobiol. 2002 Feb; 12(1):115-8.
PMID: 11861174
22
Halsey NA.
Combination vaccines: defining and addressing current safety concerns.
Clin Infect Dis. 2001 Dec 15; 33 Suppl 4:S312-8. Review.
PMID: 11709765
Jyonouchi H, Sun S & Le H.
Proinflammatory and regulatory cytokine production associated with innate and adaptive immune
responses in children with autism spectrum disorders and developmental regression.
J Neuroimmunol. 2001 Nov 1; 120(1-2):170-9.
PMID: 11694332
Hornig M & Lipkin WI.
Infectious and immune factors in the pathogenesis of neurodevelopmental disorders: epidemiology,
hypotheses, and animal models.
Ment Retard Dev Disabil Res Rev. 2001; 7(3):200-10. Review.
PMID: 11553936
Persico AM, Militerni R, Bravaccio C, Schneider C, Melmed R, Trillo S, Montecchi F, Palermo M,
Pascucci T, Puglisi-Allegra S, Reichelt KL, Conciatori M & Keller F.
No association between the 4g/5G polymorphism of the plasminogen activator inhibitor-1 gene
promoter and autistic disorder.
Psychiatr Genet. 2001 Jun; 11(2):99-103.
PMID: 11525425
Torres AR, Maciulis A & Odell D.
The association of MHC genes with autism.
Front Biosci. 2001 Aug 1; 6:D936-43. Review.
PMID: 11487481
Brudnak MA.
Application of genomeceuticals to the molecular and immunological aspects of autism.
Med Hypotheses. 2001 Aug; 57(2):186-91.
PMID: 11461171
Hornig M, Briese T & Lipkin WI.
Bornavirus tropism and targeted pathogenesis: virus-host interactions in a neurodevelopmental model.
Adv Virus Res. 2001; 56:557-82. Review.
PMID: 11450312
Hornig M, Solbrig M, Horscroft N, Weissenbock H & Lipkin WI.
Borna disease virus infection of adult and neonatal rats: models for neuropsychiatric disease.
Curr Top Microbiol Immunol. 2001; 253:157-77.
PMID: 11417134
Malek-Ahmadi P.
Cytokines and etiopathogenesis of pervasive developmental disorders.
Med Hypotheses. 2001 Mar; 56(3):321-4.
PMID: 11359354
Binstock T.
Intra-monocyte pathogens delineate autism subgroups.
Med Hypotheses. 2001 Apr; 56(4):523-31.
PMID: 11339860
Bernard S, Enayati A, Redwood L, Roger H & Binstock T.
23
Autism: a novel form of mercury poisoning.
Med Hypotheses. 2001 Apr; 56(4):462-71. Review.
PMID: 11339848
Taieb O, Baleyte JM, Mazet P & Fillet AM.
Borna disease virus and psychiatry.
Eur Psychiatry. 2001 Feb; 16(1):3-10. Review.
PMID: 11246286
Persico AM, Militerni R, Bravaccio C, Schneider C, Melmed R, Trillo S, Montecchi F, Palermo MT,
Pascucci T, Puglisi-Allegra S, Reichelt KL, Conciatori M, Baldi A & Keller F.
Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies.
Am J Med Genet. 2000 Dec 4;96(6):784-90.
PMID: 11121182
Gupta S.
Immunological treatments for autism.
J Autism Dev Disord. 2000 Oct; 30(5):475-9.
PMID: 11098887
Megson MN.
Is autism a G-alpha protein defect reversible with natural vitamin A?
Med Hypotheses. 2000 Jun; 54(6):979-83.
PMID: 10867750
Manning JT & Bundred PE.
The ratio of 2nd to 4th digit length: a new predictor of disease predisposition?
Med Hypotheses. 2000 May; 54(5):855-7.
PMID: 10859702
Hornig M, Weissenbock H, Horscroft N & Lipkin WI.
An infection-based model of neurodevelopmental damage.
Proc Natl Acad Sci U S A. 1999 Oct 12; 96(21):12102-7.
PMID: 10518583
Fiumara A, Sciotto A, Barone R, D'Asero G, Munda S, Parano E & Pavone L.
Peripheral lymphocyte subsets and other immune aspects in Rett syndrome.
Pediatr Neurol. 1999 Sep; 21(3):619-21.
PMID: 10513687
Comi AM, Zimmerman AW, Frye VH, Law PA & Peeden JN.
Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism.
J Child Neurol. 1999 Jun; 14(6):388-94.
PMID: 10385847
Connolly AM, Chez MG, Pestronk A, Arnold ST, Mehta S & Deuel RK.
Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders.
J Pediatr. 1999 May; 134(5):607-13.
PMID: 10228297
Edelson SB & Cantor DS.
Autism: xenobiotic influences.
Toxicol Ind Health. 1998 Jul-Aug; 14(4):553-63.
PMID: 9664646
24
Messahel S, Pheasant AE, Pall H, Ahmed-Choudhury J, Sungum-Paliwal RS & Vostanis P.
Urinary levels of neopterin and biopterin in autism.
Neurosci Lett. 1998 Jan 23;241(1):17-20.
PMID: 9502205
Sakic B, Szechtman H & Denburg JA.
Neurobehavioral alterations in autoimmune mice.
Neurosci Biobehav Rev. 1997 May; 21(3):327-40. Review.
PMID: 9168268
van Gent T, Heijnen CJ & Treffers PD.
Autism and the immune system.
J Child Psychol Psychiatry. 1997 Mar; 38(3):337-49. Review.
PMID: 9232480
Gupta S, Aggarwal S & Heads C.
Dysregulated immune system in children with autism: beneficial effects of intravenous immune
globulin on autistic characteristics.
J Autism Dev Disord. 1996 Aug; 26(4):439-52. No abstract available.
PMID: 8863094
Singh VK.
Plasma increase of interleukin-12 and interferon-gamma. Pathological significance in autism.
J Neuroimmunol. 1996 May; 66(1-2):143-5.
PMID: 8964908
Warren RP, Singh VK, Averett RE, Odell JD, Maciulis A, Burger RA, Daniels WW & Warren WL.
Immunogenetic studies in autism and related disorders.
Mol Chem Neuropathol. 1996 May-Aug; 28(1-3):77-81. Review.
PMID: 8871944
Scifo R, Cioni M, Nicolosi A, Batticane N, Tirolo C, Testa N, Quattropani MC, Morale MC, Gallo F
& Marchetti B.
Opioid-immune interactions in autism: behavioural and immunological assessment during a doubleblind treatment with naltrexone.
Ann Ist Super Sanita. 1996; 32(3):351-9.
PMID: 9028057
Warren RP & Singh VK.
Elevated serotonin levels in autism: association with the major histocompatibility complex.
Neuropsychobiology. 1996; 34(2):72-5.
PMID: 8904735
Haag G, Tordjman S, Duprat A, Clement MC, Cukierman A, Druon C, Jardin F, Maufras du
Chatellier A, Tricaud J & Urwand S.
[Clinical guide scale for the developmental stages of treated autism]
Psychiatr Enfant. 1995; 38(2):495-527. French.
PMID: 8657799
Daniels WW, Warren RP, Odell JD, Maciulis A, Burger RA, Warren WL & Torres AR.
Increased frequency of the extended or ancestral haplotype B44-SC30-DR4 in autism.
Neuropsychobiology. 1995; 32(3):120-3.
PMID: 8544967
Warren RP, Yonk J, Burger RW, Odell D & Warren WL.
25
DR-positive T cells in autism: association with decreased plasma levels of the complement C4B
protein.
Neuropsychobiology. 1995; 31(2):53-7.
PMID: 7760985
Bryden MP, McManus IC & Bulman-Fleming MB.
Evaluating the empirical support for the Geschwind-Behan-Galaburda model of cerebral
lateralization.
Brain Cogn. 1994 Nov; 26(2):103-67.
PMID: 7531983
Anlar B, Oktem F & Torok T.
Human parvovirus B19 antibodies in infantile autism.
J Child Neurol. 1994 Jan; 9(1):104-5. No abstract available.
PMID: 8151074
Remschmidt H.
[Psychoneuroimmunology]
Z Kinder Jugendpsychiatr. 1993 Jun; 21(2):71-2. German. No abstract available.
PMID: 8342334
Singh VK, Warren RP, Odell JD & Cole P.
Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of
autistic children.
Clin Immunol Immunopathol. 1991 Dec; 61(3):448-55. Erratum in: Clin Immunol Immunopathol
1992 Jun; 63(3):292.
PMID: 1934632
Francesetti G, Gecele M & Meluzzi A.
[Psycho immunology. II. The neuroendocrine system and the immune system in autism and
schizophrenia]
Minerva Psichiatr. 1991 Apr-Jun; 32(2):75-82. Review. Italian.
PMID: 1870415
Root-Bernstein RS & Westall FC.
Serotonin binding sites. II. Muramyl dipeptide binds to serotonin binding sites on myelin basic
protein, LHRH, and MSH-ACTH 4-10.
Brain Res Bull. 1990 Dec; 25(6):827-41.
PMID: 1705162
Yonk LJ, Warren RP, Burger RA, Cole P, Odell JD, Warren WL, White E & Singh VK.
CD4+ helper T cell depression in autism.
Immunol Lett. 1990 Sep; 25(4):341-5.
PMID: 1979061
Warren RP, Yonk LJ, Burger RA, Cole P, Odell JD, Warren WL, White E & Singh VK.
Deficiency of suppressor-inducer (CD4+CD45RA+) T cells in autism.
Immunol Invest. 1990 Jun; 19(3):245-51.
PMID: 2142123
Leboyer M, Osherson DN, Nosten M & Roubertoux P.
Is autism associated with anomalous dominance?
J Autism Dev Disord. 1988 Dec; 18(4):539-51. Review.
PMID: 3063713
26