A Preliminary Magnetic Resonance Spectroscopy Investigation Sex Differences in Gamma-Aminobutyric Acid in Autism Spectrum Disorder

Background:  The right dorsolateral prefrontal cortex (rDLPFC) and the right superior temporal sulcus (rSTS) have been implicated in social processing in autism spectrum disorder (ASD). Moreover, there is growing interest in the role of biological sex in ASD, and evidence to suggest that this might contribute to the heterogeneous nature of ASD. While the etiology of ASD remains unknown, it has been suggested that an imbalance of cortical inhibition/excitation might be associated with some of the neurobiological underpinnings of ASD. Recent research has associated gamma-aminobutyric acid (GABA, a major inhibitory neurotransmitter) concentration with the severity of ASD characteristics.

Objectives:  This study uses magnetic resonance spectroscopy (MRS) to investigate sex differences in GABA concentration (mM/L) between adults with ASD and typically developing controls. Further, this study investigates the relationship between GABA concentration at the rDLPFC and rSTS, and traits and characteristics associated with ASD.

Methods:  GABA was measured as part of a large protocol using a 3T magnetic resonance imaging (MRI) scanner. Voxels were placed at the rDLPFC and rSTS based on the participant’s structural MRI. rDLPFC GABA concentration was obtained for 25 participants (9 ASD, 16 NT), and rSTS GABA concentration was obtained for 26 (12 ASD, 14 NT) participants. Data were analyzed using LCModel software.

Results:  There were no differences in GABA concentration at either of these sites between groups, nor when data were stratified by sex. Following correction for multiple comparisons, there was a significant positive relationship between GABA concentration at the rSTS and social impairment in females with ASD.

Conclusions:  Although inconsistent with a GABAergic model of autism, these findings provide preliminary support for sex differences in neurochemical mechanisms underlying social cognition in ASD.