THE PSYCHOPHYSIOLOGY OF ADHD: FROM GENES TO
ADJUSTMENT
Convenor: William T. Utendale (Contact), Affective and Behavioural Competence,
Development Laboratory, Centre for Research in Human Development, Department of
Psychology, Concordia University, 7141 Sherbrooke Street West, Montréal, Québec
H4B-1R6, Canada (Tel : +1-514-848-2424 Ext. 2256, Email:
w_utenda@alcor.concordia.ca).
Co-convenor: Alasdair Vance, Head, Academic Child Psychiatry, Department of
Paediatrics, University of Melbourne, Royal Children’s Hospital, Murdoch Children’s
Research Institute, Melbourne, Australia (Tel: 61 3 9345 4666, Email:
avance@unimelb.edu.au).
ABSTRACT
Dysfunctional biological systems underlie many psychological disorders. There is
growing recognition across health science disciplines that psychophysiological processes
affect the ways in which children’s emotional and behavioural problems are manifested.
In this symposium, four researchers will present their work on the physiological
correlates of ADHD. The first presenter will discuss genetic differences associated with
methylphenidate response profiles among children with ADHD. The second paper will
examine differential cardiovascular reactivity among the three ADHD subtypes during a
stress induction procedure. Our third presenter will examine the relationship between
cortisol reactivity and comorbid problems during stress induction for children with
ADHD. The fourth presenter will discuss mental rotation paradigms during fMRI to
examine patterns of activation of frontal-striatal-parietal brain areas in adolescents of the
combined ADHD subtype. These four papers provide data that inform our understanding
of ADHD at a fundamental, biological level. Extrapolation from dysfunctional
physiology to behavioural manifestation, and treatment implications will be explored.
Ultimately, further physiological research may increase the efficacy of distinguishing and
treating this very problematic disorder.
RELATIONSHIP BETWEEN 5-HTT, DRD4 AND DAT1 GENOTYPES
AND METHYLPHENIDATE RESPONSE IN CHILDREN WITH
ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)
Presenter: Louise Simard, Sainte-Justine Hospital Research Centre, University of
Montreal, 3175 Sainte-Catherine Road, Montreal, Quebec, H3T 1C5 Canada
(louise.simard@umontreal.ca).
Co-Author: Anne Vilain, Sainte-Justine Hospital Research Centre, University of
Montreal, 3175 Sainte-Catherine Road, Montreal, Quebec, H3T 1C5 Canada
(vilain_anne@hotmail.com).
Co-Author: Philippe Robaey, Sainte-Justine Hospital Research Centre, University of
Montreal, 3175 Cote Sainte-Catherine, Montreal, Quebec, H3T 1C5 Canada
(philippe.robaey@umontreal.ca).
Co-Author: Genizon BioSciences, 880 McCaffrey, St. Laurent, Quebec H4T 2C7,
Canada (www.genizon.com).
Co-Author: Isabel Fortier, Genome Quebec, McGill University and Genome Quebec
Innovation Center, 740 av. Penfield, Montreal, Quebec H3A 1A4, Canada
(Isabel.fortier@mail.mcgill.ca).
ABSTRACT
Methylphenidate (MPH) is the most frequently used medication for the treatment of
ADHD; however, at least 25% of treated children do not respond to this psychostimulant.
The objective of this study was to evaluate the effect of the 5-HTT-PR, DRD4 VNTR and
DAT1 VNTR DNA variants on the MPH response in 6 to 11 year old ADHD children
enrolled in a randomized, double blind, placebo-controlled, crossover trial. Response
profiles were established under placebo and three MPH doses (15, 25 and 35 or 50 mg
depending on the child’s weight) for 52 participants. ADHD subtype distribution was as
follows: 7 (13%) hyperactive/impulsive, 19 (36%) inattentive and 26 (51%) combined.
Daily teacher and parent ratings were established using the SWAN-F questionnaire.
Potential interactions with demographic, clinical and socio-environmental factors were
also investigated. We did not observe a main effect between 5-HTT, DRD4 or DAT1
genotypes and MPH response profiles. However, the effect of 5-HTT genotype on
treatment response was modulated by socio-environment (family income and level of
parental education), genes (DAT1, DRD4) and prior MPH use. The interaction between
5HTT-PR L/L genotype and environmental stressors resulted in a lower MPH doseresponse profile. We are currently extending these data to include a comprehensive set of
tagSNPs for each of the candidate genes investigated as well as pre- and post-stress
cortisol levels to further explore this relationship. The former should greatly improve the
power of this study and the latter may allow us to test the role between 5HTT genotype,
stress and MPH response.
CARDIOVASCULAR REACTIVITY DURING STRESS INDUCTION
DIFFERENTIATES ADHD SUBTYPES
Presenter: William T. Utendale, Affective and Behavioural Competence, Development
Laboratory, Centre for Research in Human Development, Department of Psychology,
Concordia University, 7141 Sherbrooke Street West, Montréal, Québec H4B-1R6,
Canada (Tel : +1-514-848-2424 Ext. 2256, Email: w_utenda@alcor.concordia.ca).
Co-Author: Paul D. Hastings, Affective and Behavioural Competence, Development
Laboratory, Centre for Research in Human Development, Department of Psychology,
Concordia University, 7141 Sherbrooke Street West, Montréal, Québec H4B-1R6,
Canada (Email: paul.hastings@concordia.ca).
ABSTRACT
Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most pervasive childhood
mental health problems facing society. Research examining how autonomic physiological
systems are associated with ADHD has been inconclusive, often yielding contradictory
results. One confounding issue may be the heterogeneity of symptom sets exhibited by
children with ADHD. Children’s ability to self-regulate their physiological arousal under
conditions of challenge or stress is likely to be influenced by ADHD subtype. In this
investigation, 142 elementary school-aged children with ADHD wore cardiac monitors
while undergoing a stress-inducing event: having their blood drawn in a hospital clinic.
Continuously recorded cardiac inter-beat intervals were used to assess heart rate
(arousal), vagal tone (parasympathetic regulation), and SNS Index (sympathetic
regulation). Parental reports of ADHD symptomatology were assessed using the CPRS-R
and the DISC-IV. Significant variability in cardiovascular reactivity distinguished
between ADHD subtypes; in particular, children with hyperactive-impulsive problems
showed strongly atypical vagal and SNS reactivity. These results have implications for
the diagnosis and treatment of ADHD.
GENDER AND COMORBIDITY MODERATE NEUROENDOCRINE
REACTIVITY IN CHILDREN WITH ADHD
Presenter: Paul D. Hastings, Centre for Research in Human Development, Department
of Psychology, Concordia University, Montreal Quebec, H4B 1R6 Canada (Phone: 01
514-848-2424-2208 , Fax: 01 514-848-2815, paul.hastings@concordia.ca).
Co-Author: Isabel Fortier, Genome Quebec, McGill University and Genome Quebec
Innovation Center, 740 av. Penfield, Montreal, Quebec H3A 1A4, Canada
(Isabel.fortier@mail.mcgill.ca).
Co-Author: Philippe Robaey, Sainte-Justine Hospital Research Centre, University of
Montreal, 3175 Cote Sainte-Catherine, Montreal, Quebec, H3T 1C5 Canada
(philippe.robaey@umontreal.ca).
Co-Author: Louise Simard, Sainte-Justine Hospital Research Centre, University of
Montreal, 3175 Sainte-Catherine Road, Montreal, Quebec, H3T 1C5 Canada
(louise.simard@umontreal.ca).
ABSTRACT
Several investigators have examined whether children with ADHD differ in their
neuroendocrine reactivity to stress from children without problems. Although results are
inconsistent across studies, some researchers report that comorbid disruptive behavior
disorders (DBD) are more strongly associated with diminished cortisol responses to
challenge than is ADHD itself. However, these studies have had a number of limitations,
including small sample sizes, under-representation of girls, and failure to consider other
comorbid conditions. To address these limits, 155 male and 45 female elementary
school-aged children with ADHD provided waking, pre-stress, and post-stress saliva
samples, with venipuncture in a hospital clinic used as the stressor. Parents reported on
psychiatric diagnoses on the DISC-IV, and continuous problem scores on the Conners
Parent Rating Scales – Revised (CPRS-R). Girls and boys showed similar magnitudes of
cortisol elevation in response to the blood draw, but their comorbid diagnoses were
differentially associated with reactivity. Comorbid anxiety disorders were more strongly
associated with larger cortisol increases in boys than girls. Comorbid DBD were
associated with decreased reactivity in boys, but increased reactivity in girls. Parallel
results were found with the continuous measures of problems from the CPRS-R. Results
will be discussed in terms of biological models of psychopathology and the need to
recognize the roles of gender and comorbidity in children’s reactivity and functioning.
DEFICIENT SPATIAL WORKING MEMORY IN ADOLESCENTS
WITH ADHD: AN fMRI INVESTIGATION OF FRONTO-PARIETAL
NEURAL NETWORKS
Presenter: Alasdair Vance, Head, Academic Child Psychiatry, Department of
Paediatrics, University of Melbourne, Royal Children’s Hospital, Murdoch Children’s
Research Institute, Melbourne, Australia (Tel: 61 3 9345 4666, Email:
avance@unimelb.edu.au).
ABSTRACT
In this study, an fMRI mental rotation paradigm is used to investigate the patterns of
activation of frontal-striatal-parietal brain areas in adolescents with ADHD-CT compared
to age-, gender-, handedness- and performance IQ-matched healthy controls. Two, albeit
interconnected, neural network systems appeared to be activated less in the ADHD-CT
group compared to the healthy control subjects; (1) the ‘action-attentional’ system
(including BA 46,39,40) that subserves disengaged, reoriented and maintained attentional
focus and inhibition of contextually irrelevant stimuli and (2) the superior parietal (BA 7)
and middle frontal (BA 10) areas that are involved in visuospatial manipulation. In
contrast, superior and middle temporal regions appeared to be preferentially activated in
the ADHD-CT group compared with controls. These lateral temporal areas are involved
with the ventral visual stream for object recognition, particularly for manipulable objects
and for real or implied object motion. This may suggest a more object-based approach to
the mental rotation task used by the ADHD-CT group. Posterior cingulate and medial
superior prefrontal areas also showed greater activation in the ADHD-CT group. These
areas are functionally linked in the motivational shifting of attentional focus. In
conclusion, these findings suggest a widespread maturational lag affecting fronto-parietal
functional neural systems associated with more diffuse, inefficient activation of the
midline attentional cortical networks. This is consistent with emerging theoretical
models of immature, inefficient neural networks being replaced by mature, efficient
neural networks that then attempt to maintain themselves across the entire lifespan.