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

Background 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 excitatory glutamatergic system could explain underlying neuronal commonalities and differences. Methods Using magnetic resonance spectroscopy (1H-MRS), we therefore investigated the associations between glutamate concentrations in the anterior cingulate cortex (ACC), the left and right putamen, and left and right dorsolateral prefrontal cortex (DLPFC) autistic traits and psychotic-like experiences in 53 healthy individuals (28 women). Results Applying linear regressions and moderations analyses, we found that ACC glutamate, but none of the other concentrations, predicted positive-like symptoms. None of the other clinical scores was associated with altered levels of glutamate. We furthermore found that high levels of ACC glutamate are predictive of psychotic symptoms when glutamate concentrations in the right putamen were reduced, and that high levels of ACC glutamate are predictive of psychotic symptoms when disorganized traits were increased. Conclusion These results indicated that an imbalance in the glutamatergic neurotransmitter system involving cortical and subcortical regions may contribute to development of psychotic-like experiences, especially positive-like symptoms. These findings may ultimately facilitate early detection of individuals transitioning into an acute episode of psychosis. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement VD was funded by the doctoral program Translationale Medizin of the Technical University of Munich supported by Else Kroener-Fresenius-Stiftung (EKFS). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The medical research ethics committee of the Technical University of Munich gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data is available upon reasonable request to the authors.