Adam Naples, Yanghong Yang, Paul Gravel, Takuya Toyonaga, Faranak Ebrahimian Sadabad, Sheida Koohsari, Brian Pittman, Jean-Dominique Gallezot, Lauren Pisani, Caroline Finn, Sophie Cramer-Benjamin, Nicole Herman, Lindsey H. Rosenthal, Cassandra J. Franke, Bridget M. Walicki, Isabel G. Rodden, Ansel T. Hillmer, Irina Esterlis, Jim Ropchan, Nabeel Nabulsi, Yiyun Huang, Julie M. Wolf, Richard E. Carson, James C. McPartland, David Matuskey
OBJECTIVE: Autism spectrum disorder is a prevalent and heterogeneous condition with features ranging from social and communication differences to sensory sensitivities. Differences in excitatory neurotransmission have been identified in autism, but the molecular underpinnings are poorly understood. To investigate the mechanism underlying these observed differences, the authors assessed glutamatergic receptor density in autistic adults using positron emission tomography (PET) and related it to a functional EEG measure of excitatory activity. METHODS: were calculated using Spearman's rho. RESULTS: Across all brain regions, mGlu5 availability was significantly lower (by ~15%) in autistic relative to neurotypical control participants. Group differences were generally greatest in the cerebral cortex. Within the autistic group, mGlu5 availability in all regions was significantly correlated with the slope of the EEG (e.g., cerebral cortex, r=0.67), such that shallower slope was associated with lower mGlu5 availability. CONCLUSIONS: This brain-wide investigation of mGlu5 availability with PET revealed pervasive lower mGlu5 availability across multiple brain areas in autism. Additionally, multimethod analyses revealed associations with a noninvasive electrophysiological index of excitatory neurotransmission. These results indicate that lower brain-wide mGlu5 availability may represent a molecular mechanism underlying altered excitatory neurotransmission that has the potential to stratify the heterogeneous autism phenotype.