The DRD3 Gene and Striatum in Autism Spectrum Disorder (ASD)

Background: Recently the SNP rs167771 (DRD3) was found to be associated with ASD in two independent samples. Further exploration showed that rs167771 polymorphisms correspond to different levels of higher order stereotyped behaviour in ASD (Staal, 2012). 

Objectives: Since the DRD3 receptor is also highly expressed in the striatum, we tested the hypothesis that changes in striatum were related to polymorphisms of rs167771 in autism.

Methods: To test this hypothesis, the volume of striatum (caudate, putamen, gl pallidus) and the whole brain were measured using freesurfer on anatomical MRI scans from 86 subjects with ASD. Behavioural assessment included the ADI-R, ADOS, IQ assessment and genotyping of rs167771. 

Results: MANCOVA showed a significant association between the rs167771 minor allele and striatum volume (F= 2.582 (df= 4); p=.046). In an explorative follow up analysis, the volume of striatum correlated with higher order stereotype behaviour (R=.278; p=.040).

Conclusions: These data suggest that there may be a relationship between a common variant of the DRD3 receptor gene, striatum volume and stereotyped behaviour in ASD. If this preliminary result replicates, future studies will need to address whether the observed relationships are specific to ASD or whether they represent a broader biological mechanism.

References: Staal WG, de Krom M, de Jonge MV. Brief Report: The Dopamine-3-Receptor Gene (DRD3) is associated with Specific Repetitive Behavior in Autism Spectrum Disorder (ASD). J Autism Dev Disord. 2012 May;42(5): 885-8.