Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder

The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N=66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (ηp(2) ) was used to gauge the magnitude of group differences: 0.01-0.06=small, 0.06-0.14=moderate and >0.14=large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers' (ηp(2)=0.10) and teachers' (ηp(2)=0.06) ratings than noncarriers, but the latter was marginally significant (P=0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (ηp(2)=0.07) and obsessions-compulsions (ηp(2)=0.08). Findings for maternal ratings of separation anxiety were marginally significant (P=0.08, ηp(2) =0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P=0.05) for teachers' ratings of oppositional behavior and mothers' ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples.