Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder

Abstract

<h3>Purpose</h3><p>Opioid and dopamine receptor systems are implicated in the pathoetiology of autism, but in vivo human brain imaging evidence for their role remains elusive.</p><h3>Methods</h3><p>Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11 C]raclopride (D2R) and [11 C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 24 age and sex matched controls. A whole brain voxel-wise analysis was tested with Student´s t-test and regional group differences in D2R and MOR receptor availabilities as total and separate were tested with linear mixed models also examining the associations between regional receptor availabilities with correlations.</p><h3>Results</h3><p>There were no group differences in whole-brain voxel-wise analysis of D2R, but ROI analysis revealed a lower overall mean availability in striatum of the ASD compared to controls. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens and globus pallidus of the ASD group. The whole-brain voxel-wise analysis of MOR revealed cuneal/precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens.</p><h3>Conclusions</h3><p>These alterations may translate to disrupted modulation of social motivation and reward in ASD.</p>