Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder

Abstract

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents' ratings) was associated with DAT1 intron8 (ηp(2)=.063) and rs2283265 (ηp(2)=.044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (ηp(2)=.065) and depression (ηp(2)=.059), and for DRD2 rs2283265, depression (ηp(2)=.053). DRD2 rs2283265 was associated with teachers' global ratings of ADHD (ηp(2)=.052). DAT1 intron8 was associated with parent-rated hyperactivity (ηp(2)=.045) and both DAT1 9/10 VNTR (ηp(2)=.105) and DRD2 rs2283265 (ηp(2)=.069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples.

Keywords: ADHD; Autism; Autism spectrum disorder; DAT1; DRD2; Depression; Emotion dysregulation.

Figure 1

Association of DAT1 intron8 VNTR 5-6 and 6-6 repeat genotypes and severity of oppositional defiant disorder (ODD), generalized anxiety disorder (GAD), separation anxiety disorder (SAD), and major depressive episode (MDE) symptoms controlling for severity of ADHD symptoms. Group differences were significant (p<0.05) for GAD and MDE and marginally significant (p=0.056) for ODD.

Figure 2

Mean severity of parent-rated emotion dysregulation symptoms (EMD) for DAT1 intron8 5/6 repeat VNTR (5-6, 6-6) and DRD2 rs2283265 (G-G, G-T) genotype groups. The interaction was not significant (p=0.41).