Modulation of executive function in children with Attention DeficitHyperactivity Disorder by allelic variants of the catechol-O-methyltransferase gene and three varying doses of methylphenidate

An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. Furthermore, since methylphenidate (MPH), the primary pharmacological drug in ADHD, may exert its effects, at least in part, through PFC dopaminergic pathways, we investigated the relationship between the COMT polymorphism and acute neuropsychological and behavioural response to three varying doses of MPH. Children with ADHD showed improvement on measures of both cognitive and motor behaviours under MPH, although improvement within each functional domain appeared to follow distinctive dose-response patterns possibly reflecting different neurobiological pathways. No genotype effects were observed on any measures of cognitive or motor behaviour or on the response of cognitive or motor behaviours to MPH