The glutamate hypothesis of schizophrenia proposes that the dysfunction in the glutamatergic neurotransmitter system, particularly involving N-methyl-d-aspartate(NMDA)-receptor hypofunction, is linked to the pathophysiology of schizophrenia. Previous studies also showed that alterations in the primary excitatory neurotransmitter, glutamate, are linked to brain functional connectivity. Furthermore, the NMDA-receptor hypofunction is hypothesised to underlie abnormalities in the framework of predictive coding. This Bayesian inference theory implicates that an overweighting of prior beliefs underlies the formation of hallucinations in schizophrenia. However, the interplay of molecular biology, functional connectivity and underlying neurocomputational mechanisms for psychosis remains still unclear.
Using magnetic resonance spectroscopy (¹H‐MRS), functional magnetic resonance imaging (fMRI) and a language prediction task, we investigated this relationship between glutamate concentrations in the anterior cingulate cortex (ACC) and the left dorsolateral prefrontal cortex (lDLPFC), functional connectivity (FC) and psychotic‐like experiences (Schizotypal Personality Questionnaire) in 53 healthy individuals (26 women). We conducted a seed-based connectivity analysis, using the ACC and the lDLPFC as the seeds of interest for two separate analyses. We then investigate associations between FC, language task parameters, subclinical scores and glutamate levels in linear regression models.
Preliminary results show that ACC glutamate and prior overweighting predict the connectivity strength of the ACC. Therefore, this study proposes that molecular biology, functional connectivity and neurocomputational mechanisms may interact to develop psychotic-like experiences, and could potentially serve as a promising indicator for identifying individuals at an early stage.