Elevated brain glutamine levels in adults with autism spectrum disorder: A 7T MRS study

Alterations in excitatory neurotransmitters, involving the glutamate (Glu) and glutamine (Gln) cycle, as well as inhibitory neurotransmission, GABA, are implicated in the pathophysiology of autism spectrum disorder (ASD). Although magnetic resonance spectroscopy (MRS) holds promise for assessing these metabolites, conventional 3 T MRI does not robustly measure them, leaving the neurochemical pathophysiology of ASD insufficiently understood. 7 T MRI enables reliable assessments of these neurometabolites by enhancing the signal-to-noise ratio and improving the spectral resolution, particularly in distinguishing neuroactive Glu from its metabolic precursor, Gln. The current 7 T MRS study has two primary objectives: first, to investigate neurometabolite levels in adults with ASD to elucidate its neurochemical pathophysiology, and second, to examine their association with symptoms of ASD. Thirty-three adults with ASD (mean age = 31 years) and 52 age-matched control adults were included. The neurometabolite levels of Glu, Gln, and GABA were assessed in the anterior cingulate cortex (ACC), thalamus, and right temporo-parietal junction (TPJ), with most quantifications passing quality checks. Analysis of covariance revealed significant effects of diagnosis on Gln in the thalamus (p = 0.008) and right TPJ (p = 0.006), indicating elevated Gln levels in these regions in the ASD group. Among social communication and restricted and repetitive behaviors, significant negative correlations were observed in the ASD group between Gln levels and sensory symptoms. These findings suggest that alterations in the excitatory neurotransmission regulation, presumably increased cycling of the Gln-Glu circuit, may underlie the pathophysiology of ASD.