Influence of candidate ADHD genes on reward processing and working memory in adult ADHD patients and healthy subjects.

Introduction and objectives: ADHD is a highly heritable disorder, which is attributable to multiple genes of small effect size. Understanding the modes of action of those genes already known can aid in unraveling biological mechanisms underlying ADHD. For that goal we built a large database of adult ADHD patients and controls extensively characterized using cognitive testing and functional imaging. Methods: We are currently focusing on functional genetic variants in two ADHD genes, NOS1 and DRD4, and their effects on cognitive and motivational functioning in ADHD. Results: Reward-related impulsivity and striatal activity are influenced by the NOS1 gene in ADHD patients (n = 69) and controls (n = 29). Working memory performance was not affected by DRD4 genotype, but prefrontal cortex activity was. Discussion: Our findings fit into a model in which ADHD genes act via glutamatergic and dopaminergic/serotonergic systems (NOS1) and signaling downstream of dopamine (DRD4) to affect brain function in subcortical and cortical areas. Conclusion: Functional effects of ADHD genes were more readily observed when analyzing the activity of relevant brain structures than at a behavioral level. We think this approach is an efficient way to elucidate ADHDs biological mechanisms. [ABSTRACT FROM AUTHOR]