Association of ADHD, tics, and anxiety with dopamine transporter (DAT1) genotype in autism spectrum disorder

Abstract

Background Autism spectrum disorder (ASD) is associated with high rates of psychiatric disturbance to include attention-deficit/hyperactivity disorder (ADHD), tic disorder, and anxiety disorders. The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism located in the 3′-untranslated region of the dopamine transporter gene (DAT1) and the severity of these symptoms as well as the association between the DAT1 DdeI polymorphism and severity of tics. Methods Parents (n = 62) and teachers (n = 57) completed a DSM-IV-referenced rating scale for 67 children with ASD. Results According to parent ratings, children with the 10-10 repeat allele (versus a combined group of all other genotypes) exhibited less severe symptoms of hyperactivity and impulsivity as well as less severe language deficits. Teacher ratings indicated that social anxiety and tic symptoms were more severe for children with the 10-10 genotype versus all others. Exploratory analyses provided preliminary support for the notion that heterozygosity (9–10 repeat genotype) may be a risk/protective factor. There were no associations of tic severity with the DAT1 DdeI polymorphism. Conclusion Collectively, these results suggest that the extraordinary variability in ASD clinical phenotypes may be explained in part by the same genes that are implicated in a host of other psychiatric disorders in non-ASD populations. Nevertheless, replication with independent samples is necessary to confirm this preliminary finding.

Brain Serotonin and Dopamine Transporter Bindings in Adults With High-Functioning Autism

“…29 Furthermore, it has been suggested that the 9-and 10-repeat alleles of the dopamine transporter may be associated with hyperactivity, impulsivity, social anxiety, and tic symptoms in autistic children. 30 In a PET study of autistic children, low levels of medial prefrontal dopaminergic activity were observed under anesthesia, 31 whereas increased dopamine D 2 receptor binding in the whole caudate and putamen has also been demonstrated. 32 These findings suggest that the alteration of both the serotonin and the dopamine systems is a feature of autism, although these findings remain equivocal and inconclusive.…”

Dopaminergic Dynamics Contributing to Social Behavior

“…A dopamine D1 receptor (DRD1) haplotype as well as DRD3 single-nucleotide polymorphisms have been associated with increased risk for ASD (Hettinger et al 2008;Staal 2014). Mutations in the dopamine transporter (DAT) have also been associated with ASD (Bowton et al 2014); DAT mutations that result in increased expression of the transporter, and thus likely lower synaptic levels of DA, are associated with increased social anxiety in ASD children (Gadow et al 2008). Together, these data suggest a deficit in social reward processing in ASD accompanied by genetic and functional abnormalities in the mesolimbic DA pathway.…”

A Dopamine Hypothesis of Autism Spectrum Disorder

“…It is likely that other neurobiological anomalies co-occur, given the spectrum's extreme heterogeneity. Nonetheless, dopamine signaling anomalies have been associated with several ASD comorbidities, such as ADHD, anxiety, tics [45] , and executive function deficits [46] .…”