Polymorphisms in Dopamine System Genes DAT1 and DRD4 are Associated with Disinhibitory Psychopathology in Adolescence

Abstract

The specificity of genetic influence upon childhood disorders of behavioral disinhibition is uncertain. Polymorphisms in dopamine system genes have been implicated in the contribution of risk for attention-deficit/hyperactivity disorder (ADHD), and other externalizing behavior disorders, but the range of behaviors affected by variation in these genes is ambiguous. To address this problem, we examined the relationship between polymorphisms in the dopamine receptor D4 (DRD4) and dopamine transporter (DAT1) genes and the symptoms and diagnoses of ADHD, ADHD subtypes, oppositional defiant disorder (ODD), and conduct disorder (CD) in 2902 individuals from a population-based twin sample. We observed an association between risk alleles in both DAT1 and DRD4 polymorphisms and increased risk for ADHD, but no main effects of variation in these genes upon risk for ODD or CD. Furthermore, the risk contributed by DAT1 and DRD4 to ADHD was not general; risk alleles in each gene were associated with specific patterns of changes in ADHD subtypes and symptom dimensions.