ADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes

Abstract

ADHD is a major burden in adulthood, where co-morbid conditions such as depression, substance use disorder and obesity often dominate the clinical picture. ADHD has substantial shared heritability with other mental disorders, contributing to comorbidity. However, environmental risk factors exist but their interaction with genetic makeup, especially in relation to comorbid disorders, remains elusive. This review for the first time summarizes present knowledge on gene x environment (GxE) interactions regarding the dopamine system. Hitherto, mainly candidate (GxE) studies were performed, focusing on the genes DRD4, DAT1 and MAOA. Some evidence suggest that the DRD4 exon 3 variable number tandem repeat (VNTR) and MAOA uVNTR may mediate (GxE) interactions in ADHD generally, and comorbid conditions specifically. For other polymorphisms, evidence is contradictory and less convincing. Particularly lacking are longitudinal studies testing the interaction of well-defined environmental with polygenic risk scores reflecting the dopamine system in its entirety. Only such an approach would be less susceptible to false-positive findings and provide clues on how genes could interact with non-genetic factors to shape psychopathology over the life span.