The −1021 C/T DBH polymorphism is associated with neuropsychological performance among children and adolescents with ADHD

Catecholaminergic imbalance has increasingly been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The enzyme dopamine-β-hydroxylase (DβH)—critical to catecholaminergic regulation—is under strong genetic control, with the −1021 C/T polymorphism accounting for up to 50% of the enzymatic activity. This work aimed to investigate association between this functional polymorphism and the performance of children and adolescents with ADHD in neuropsychological measures of executive function (EF). Sixty-four drug-naive patients with ADHD undertook a Continuous Performance Test and the Wisconsin Card Sorting Test. By means of a factorial analysis, a composite measure of EF was extracted. Performance according to genotypic group was analyzed, including age as a confounder. In addition, a family-based association test was conducted as a confirmatory analysis. Principal components analysis of neuropsychological measures loaded two factors that explained 83.8% of total variance. Cognitive performance, as measured by the composite score, showed significant difference between genotypic groups after adjustment for age (P = 0.002). The CC homozygosity was associated with a diminished global EF performance, a result that was corroborated by the intra-familial analysis. The present study demonstrated an association between the neuropsychological performance of children with ADHD and a functional polymorphism in the promoter region of the DBH gene. The refinement of the ADHD phenotype by means of composite measures of EF can contribute to uncover the molecular underpinnings of ADHD. © 2007 Wiley-Liss, Inc.