Association between increased anterior cingulate glutamate and psychotic-like symptoms, but not autistic traits

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 alterations are already present in subclinical traits of these disorders. The literature proposes that alterations 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 (28 women). To investigate the contributions of glutamate concentrations in different cortical and subcortical regions to symptom expression and their interactions, we used linear regression and moderation analyses. We found that glutamate concentration in the ACC but in none of the other regions predicted positive-like symptoms. None of the other clinical scores was associated with altered levels of glutamate. Specifying this finding, the moderation analysis showed that increased ACC glutamate was predictive of positive-like symptoms when glutamate concentrations in the right putamen were reduced, and that increased ACC glutamate was predictive of positive-like symptoms when disorganized traits were attenuated. This study provides evidence that an imbalance in the glutamatergic neurotransmitter system involving cortical and subcortical regions is linked to the expression of psychotic-like experiences, especially positive-like symptoms. These findings may facilitate the detection of individuals transitioning into an acute episode of psychosis.