11 C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults

• Published in: Molecular psychiatry 2024-10
• Main Authors: Matuskey, David, Yang, Yanghong, Naganawa, Mika, Koohsari, Sheida, Toyonaga, Takuya, Gravel, Paul, Pittman, Brian, Torres, Kristen, Pisani, Lauren, Finn, Caroline, Cramer-Benjamin, Sophie, Herman, Nicole, Rosenthal, Lindsey H, Franke, Cassandra J, Walicki, Bridget M, Esterlis, Irina, Skosnik, Patrick, Radhakrishnan, Rajiv, Wolf, Julie M, Nabulsi, Nabeel, Ropchan, Jim, Huang, Yiyun, Carson, Richard E, Naples, Adam J, McPartland, James C
• Format: Article
• Language: English
• ISSN: 1476-5578

The neural bases of autism are poorly understood at the molecular level, but evidence from animal models, genetics, post-mortem studies, and single-gene disorders implicate synaptopathology. Here, we use positron emission tomography (PET) to assess the density of synapses with synaptic vesicle glycoprotein 2A (SV2A) in autistic adults using C-UCB-J. Twelve autistic (mean (SD) age 25 (4) years; six males), and twenty demographically matched non-autistic individuals (26 (3) years; eleven males) participated in a C-UCB-J PET scan. Binding potential, BP , was the primary outcome measure and computed with the centrum semiovale as the reference region. Partial volume correction with Iterative Yang was applied to control for possible volumetric differences. Mixed-model statistics were calculated for between-group differences. Relationships to clinical characteristics were evaluated based on clinician ratings of autistic features. Whole cortex synaptic density was 17% lower in the autism group (p = 0.01). All brain regions in autism had lower C-UCB-J BP compared to non-autistic participants. This effect was evident in all brain regions implicated in autism. Significant differences were observed across multiple individual regions, including the prefrontal cortex (-15%, p = 0.02), with differences most pronounced in gray matter (p