Specific Association Patterns Between Brain Glutathione Levels, Myelination, and Functional Connectivity in Adults With Autism Spectrum Disorder

Recent studies have implicated oxidative stress in the pathophysiology of autism spectrum disorder (ASD). Postmortem brain studies have revealed decreased levels of the reduced form of glutathione (GSH), an important antioxidant, in some brain regions in individuals with ASD; however, in vivo evidence is lacking. Using proton magnetic resonance spectroscopy, T₁-weighted/T₂-weighted ratio-derived myelin maps, resting-state functional magnetic resonance imaging (MRI), and cognitive tasks, we examined whether brain GSH levels are lower in individuals with ASD than in those with typical development (TD) and explored ASD-specific association patterns between brain GSH levels, myelination, functional connectivity, and behavioral characteristics. Data from 30 adults with ASD and 27 adults with TD were analyzed. Contrary to our hypothesis, GSH levels in the left temporoparietal junction (TPJ) were higher in the ASD group than in the TD group. Using individual myelin maps, we found a significant group difference in the correlation between left middle frontal gyrus (MFG) myelination and left TPJ GSH levels. Multivariate pattern analysis of resting-state functional MRI revealed that whole-brain functional connectivity patterns from the left MFG differed between the groups in their association with left MFG myelination. Finally, we found a significant group difference in the correlation between emotion recognition ability and the functional connectivity of the left MFG with the bilateral occipitoparietal junction. In conclusion, our findings demonstrate an ASD-specific pattern of associations between left TPJ GSH levels, left MFG myelination, whole-brain functional connectivity patterns of the left MFG, and cognitive phenotype, which suggests compensatory neural mechanisms in ASD.