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Objectives: Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, [...]

Objective: To assess the one-year period prevalence of stimulant combination therapy and switching in children/ adolescents with attention deficit/hyperactivity disorder (ADHD) in Quebec, Canada. Method: Patients aged 6-17 years, with at least two ADHD diagnosis codes documented in different visits and at least 30 days' supply of a stimulant during their most recent one-year observation period were selected from the Regie de l'assurance maladie du Quebec database (03/2007-02/2012). Combination therapy was defined as at least 30 consecutive days of concomitant use of multiple stimulants with different active moieties, or use of a stimulant and another psychotropic medication. Therapy switching was defined as a prescription claim for a new psychotropic medication less than 30 days before or after the end of supply of a stimulant. The one-year period prevalence of therapy combination and switching was calculated. Results: The one-year period prevalence of combination therapy and switching among 9,431 children and adolescents with ADHD treated with stimulants was 19.8% and 18.7%, respectively. The most frequent combination categories were atypical antipsychotics (AAP: 10.8%), atomoxetine (ATX: 5.5%) and clonidine (5.3%). The most frequent switched-to categories were other stimulants (7.9%), AAP (5.5%) and ATX (4.7%). Conclusions: Approximately one in five children/adolescents with ADHD on a stimulant experienced combination therapy or therapy switching; however, the majority of the medications used in combination or switching were not label-indicated for the treatment of ADHD in Canada. These results highlight the need for further research to evaluate the risk-benefit of stimulant combination and switching in children and adolescents with ADHD. [ABSTRACT FROM AUTHOR]

We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of SLC6A3, as indicated by a significant (p=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.Neuropsychopharmacology (2007) 32, 1370–1376. doi:10.1038/sj.npp.1301240; published online 25 October 2006 [ABSTRACT FROM AUTHOR]

Background: 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. Methods: The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. Results: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05]. Conclusions: Contrary to the observed association between WCST performance and the Val108/ 158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD. [ABSTRACT FROM AUTHOR]