title: COMT Val108/158Met polymorphism and the modulation of task-oriented behavior in children with ADHD.
abstract: It has been suggested that the symptoms of attention-deficit/hyperactivity disorder (ADHD), including inattention and/or hyperactivity/impulsivity, translate into deficits in task-oriented behavior or problem-focused activity. The frontosubcortical dopamine pathway has been implicated in ADHD. One of the key modulators of extracellular dopamine levels in the prefrontal cortex is catechol-O-methyltransferase (COMT). The objective of this study was to examine the association of the COMT Val(108/158)Met polymorphism with (1) task-oriented behavior in children with ADHD, and (2) response of this behavior given methylphenidate (MPH) treatment. Children of Caucasian ethnicity, having ADHD (n=188), were assessed using the Restricted Academic Situation Scale (RASS). The RASS uses a simulated academic environment within the research clinic, to assess the child's ability for independent, sustained orientation to an assignment of math problems. Each child was administered placebo and MPH (0.5 mg/kg in a divided b.i.d. dose), each for a 1-week period, in a randomized, double-blind, crossover trial. On day 3 of the respective treatment week, the child was administered placebo/MPH in the clinic, and the acute change in behavior (before and 1 h after treatment) was evaluated on the RASS. Analysis was carried out using mixed model analysis of variance. Significant main effects of COMT genotype (F(2,184)=5.12, p=0.007) and treatment (F(1,184)=44.26, p<0.001) on task-oriented behavior were observed. However, no genotype by treatment interaction was observed. These results suggest that the COMT Val(108/158)Met polymorphism modulates task-oriented behavior, but it does not modulate the response of this behavior with MPH treatment.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: Sarojini
authors.initials: S
authors.lastname: Sengupta
authors.forename: Natalie
authors.initials: N
authors.lastname: Grizenko
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: George
authors.initials: G
authors.lastname: Schwartz
authors.forename: Johanne
authors.initials: J
authors.lastname: Bellingham
authors.forename: Anna
authors.initials: A
authors.lastname: Polotskaia
authors.forename: Marina Ter
authors.initials: MT
authors.lastname: Stepanian
authors.forename: Yukiori
authors.initials: Y
authors.lastname: Goto
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology* / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D018592:Cross-Over Studies; D004252:DNA Mutational Analysis; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000187:drug effects / Q000502:physiology; D008715:Methionine / Q000235:genetics; D008774:Methylphenidate / Q000494:pharmacology; D015990:Placebo Effect; D011110:Polymorphism, Genetic / Q000235:genetics*; D013850:Thinking / Q000187:drug effects / Q000502:physiology; D014633:Valine / Q000235:genetics
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine