Glutamate levels in the medial prefrontal cortex (mPFC) are significantly elevated in treatment-naive individuals during their first episode of psychosis (FEP) compared to both healthy controls and patients with chronic schizophrenia.
In never-medicated chronic schizophrenia patients, glutamate levels do not significantly differ from healthy controls, suggesting that glutamatergic dysregulation may be a transient feature of the early illness phase rather than a persistent trait.
Higher mPFC glutamate levels in the FEP group are inversely correlated with cognitive performance, specifically in verbal and visual learning domains.
The findings underscore the necessity of stage-specific clinical trials, particularly for medications targeting the glutamatergic system, such as mGluR2/3 agonists.
Background: The Evolution of the Glutamate Hypothesis
