An Association Between Serotonin 1A Receptor, Gray Matter Volume, and Sociability in Healthy Subjects and in Autism Spectrum Disorder

Central serotonin is an important molecular pathway, involved in the regulation of social behavior and gray matter volume (GMV). In men with autism spectrum disorders (ASD), the serotonergic system and the GMV have been found disrupted. Here, we investigated the relation between serotonin, GMV, and social personality in men with typical development (TD) and in men with ASD. We combined anatomical magnetic resonance imaging, Positron emission tomography scan with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine radioligand and revised NEO personality inventory personality questionnaire to examine the association between serotonin 1A receptor (5-HT1A R) binding potential, GMV and social personality in 24 adult male TD subjects and 18 male men with ASD. In both groups, we found a positive correlation between 5-HT1A R binding potential and GMV in a region dependent manner. In the TD group, we observed a negative correlation between 5-HT1A R and GMV in the left and right posterior putamen. 5HT1A R binding and GMV in the putamen further correlated with social personality scores in the TD group. None of these associations were found in men with ASD, although no differences were observed for 5-HT1A R concentration among the two groups. Our findings point to a deregulation of 5-HT1A R density in the striatum of men with ASD, a failure that might contribute to their social disturbances. Serotonin is suspected to be involved in the pathophysiology of autism. We provide evidence for a role of serotonin 1A receptor in social behavior through a specific regulation of GMV in the putamen region in neurotypical subjects but not in men with autism. This suggests a potential impairment of the serotonergic system in men with autism which may contribute to patients' social disturbances. Our findings suggest further investigation on the role of serotonin 1A receptor and its activity in the striatum to regulate social behavior. LAY SUMMARY: Serotonin is suspected to be involved in the pathophysiology of autism. We provide evidence for a role of serotonin 1A receptor in social behavior through a specific regulation of gray matter volume in the putamen region in neurotypical subjects but not in men with autism. This suggests a potential impairment of the serotonergic system in men with autism which may contribute to patients' social disturbances. Our findings suggest further investigation on the role of serotonin 1A receptor and its activity in the striatum to regulate social behavior.