Attention deficit and hyperactivity disorder: review of genetic association studies

Abstract

Attention Deficit and Hyperactivity Disorder (ADHD) is a common idiopathic childhood neurodevelopmental disorder, exacting a significant clinical and public health toll. It impairs schooling and social adaptation, resulting in high rates of depression, conduct disorder, school dropouts, and substance abuse, and necessitating exposure of many children to prolonged courses of stimulant psychotropic medication. Although the biological basis of ADHD is unknown, it has been shown to possess considerable heritability. Candidate gene association studies proved to be a productive strategy leading to replicated association findings of genetic loci contributing to susceptibility to ADHD. Based on the mechanism of action of stimulant drugs effective in the alleviation of ADHD symptoms, current association studies have focused mainly on dopaminergic genes. Promising exploratory findings have also been reported for genes affecting other neurotransmitter systems. The current article reviews the rationale, methodology, and main findings in the field, and outlines future directions. Locating the actual genes mediating ADHD susceptibility will have far reaching implications for understanding the pathophysiology of ADHD as well as for understanding mechanisms of therapeutic drug action and genetic determinants of response.