Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder

Summary

To our knowledge, this is the first study to examine both GABA concentrations and GABAAreceptor binding densities simultaneously in any psychiatric population. It is also the first neuroimaging study to investigate the role of the GABAergic system in regions of the thalamocortical network, as it relates to HFA with ASD. We show that, despite no group differences in GABAA receptor densities, GABA concentrations in the left DLPFC are higher in HFA with ASD, compared to TD controls. Furthermore, GABA concentrations in the thalami correlate with AQ and RAADS-R scores in a gender-specific manner in HFA with ASD, but not in TD controls. Remarkably, higher thalamic GABA concentrations are associated with lower socio-communicative symptom severity in males with ASD, and with higher symptom severity in females with ASD. We conclude that thalamic and prefrontal GABA levels are altered in a region-dependent and gender-specific manner in HFA with ASD. Our findings are important steps toward identifying molecular neuroimaging markers of socio-communicative function in individuals with ASD, thus aiding the development of assessment tools to evaluate neural circuits and interventions targeting core symptoms of ASD.

Figure

Fung LK, Flores RE, Gu M, Sun KL, James D, Schuck RK, Jo B, Park JH, Lee BC, Jung JH, Kim SE, Saggar M, Sacchet MD, Warnock G, Khalighi MM, Spielman D, Chin FT, Hardan AY. Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder. Mol Psychiatry. 2020 May 6. doi: 10.1038/s41380-020-0756-y. Epub ahead of print. PMID: 32376999.