In vivo imaging of synaptic density in psychotropic-free adults with autism spectrum disorder: a [¹¹C]UCB-J PET study

Synaptic dysfunction has been proposed as a key biological mechanism underlying autism spectrum disorder (ASD), yet findings from animal, genetic, postmortem, and molecular imaging studies remain inconsistent. Using positron emission tomography with [¹¹C]UCB-J, a radioligand that binds to synaptic vesicle glycoprotein 2 A and serves as an index of synaptic density, the present study investigated standardized uptake value ratio (SUVR) of [¹¹C]UCB-J in 20 unmedicated adult males with high-functioning ASD and 21 typically developed control adult males. Both voxel-wise whole-brain and region-of-interest analyses across multiple brain regions revealed no significant group differences in [¹¹C]UCB-J SUVR. These results remained unchanged after adjusting for potential confounders (i.e., full-scale IQ, trait and state anxiety, and depressive tendency) that differed between groups. Within the ASD group, [¹¹C]UCB-J SUVR in the left anterior and medial temporal lobe showed a significant positive correlation with the scores of restricted and repetitive behaviors (RRB), a core symptom of ASD, in the Autism Diagnostic Observation Schedule-2nd Edition. Contrary to previously reported pervasive reduction of synaptic density in individuals with ASD-most of whom were taking psychotropic medications-the current results, obtained using the same radioligand ([¹¹C]UCB-J) as in the previous study, suggest potential heterogeneity in the contribution of synaptic pathology to ASD. Although this exploratory finding requires replication in larger cohorts, the observed association between [¹¹C]UCB-J SUVR and RRB severity serves as a hypothesis-generating indicator of synaptic involvement of the behavioral rigidity in ASD. Together, these findings highlight the complexity of ASD-related synaptic pathology.