Association between increased anterior cingulate glutamate and psychotic-like experiences, but not autistic traits in healthy volunteers

Despite many differences, autism spectrum disorder and schizophrenia spectrum disorder share environmental risk factors, genetic predispositions as well as neuronal abnormalities, and show similar cognitive deficits in working memory, perspective taking, or response inhibition. These shared abnormalities are already present in subclinical traits of these disorders. The literature proposes that changes in the inhibitory GABAergic and the excitatory glutamatergic system could explain underlying neuronal commonalities and differences. Using magnetic resonance spectroscopy (1H-MRS), we investigated the associations between glutamate concentrations in the anterior cingulate cortex (ACC), the left/right putamen, and left/right dorsolateral prefrontal cortex and psychotic-like experiences (Schizotypal Personality Questionnaire) and autistic traits (Autism Spectrum Quotient) in 53 healthy individuals (26 women). To investigate the contributions of glutamate concentrations in different cortical regions to symptom expression and their interactions, we used linear regression analyses. We found that only glutamate concentration in the ACC predicted psychotic-like experiences, but not autistic traits. Supporting this finding, a binomial logistic regression predicting median-split high and low risk groups for psychotic-like experiences revealed ACC glutamate levels as a significant predictor for group membership. Taken together, this study provides evidence that glutamate levels in the ACC are specifically linked to the expression of psychotic-like experiences, and may be a potential candidate in identifying early risk individuals prone to developing psychotic-like experiences.