Specific Association Patterns Between Brain Glutathione Levels, Myelination, and Functional Connectivity in Adults...

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Background:

• Oxidative stress is implicated in autism spectrum disorder (ASD) pathophysiology.
• Reduced glutathione (GSH) levels were observed postmortem in some brain regions in ASD, but in vivo evidence is limited.
• Understanding in vivo brain biochemistry in ASD is crucial for identifying neural mechanisms.

Purpose of the Study:

• To investigate in vivo brain glutathione (GSH) levels in adults with ASD compared to typical development (TD).
• To explore associations between GSH levels, myelination, functional connectivity, and cognitive characteristics in ASD.
• To identify ASD-specific neural patterns and potential compensatory mechanisms.

Main Methods:

• Proton magnetic resonance spectroscopy (MRS) to measure brain GSH.
• T1/T2-weighted ratio-derived myelin maps.
• Resting-state functional MRI (fMRI) for functional connectivity analysis.
• Cognitive tasks assessing behavioral characteristics.

Main Results:

• Contrary to hypothesis, higher GSH levels were found in the left temporoparietal junction (TPJ) in the ASD group.
• Significant group differences were observed in the correlation between left middle frontal gyrus (MFG) myelination and left TPJ GSH levels.
• ASD-specific associations were found between MFG myelination, whole-brain functional connectivity, and emotion recognition.

Conclusions:

• Findings reveal an ASD-specific pattern linking left TPJ GSH, MFG myelination, and functional connectivity.
• These patterns suggest the presence of compensatory neural mechanisms in adults with ASD.
• The study provides novel in vivo insights into brain biochemistry and neural organization in ASD.