AbstractConverging lines of evidence suggest that glutamatergic dysfunction may contribute to the pathophysiology of first episode psychosis. We investigated whether first episode psychosis patients free from all pharmacological treatments and illicit substances show cortical glutamatergic alterations. One-hundred and eleven volunteers including 65 healthy volunteers and 46 first episode psychosis patients free from all pharmacological treatments (28 drug naïve) underwent a proton magnetic resonance spectroscopy scan measuring glutamate levels in the bilateral anterior cingulate cortex. Symptom severity was measured using the Positive and Negative Syndrome Scale (PANSS) and cognition was measured using the Wechsler Adult Intelligence Scale (WAIS) digit symbol test. There were no differences in glutamate levels between patients and controls. These findings remained unchanged when adjusting for the effects of age, sex and ethnicity or when restricting the analyses to patients who were both medication naïve to all pharmacological treatments and illicit substances. Whilst these findings do not preclude glutamatergic alterations in psychosis, methodological advances are needed for us to investigate whether patients show alterations in other aspects of glutamate function, such as pre-synaptic glutamate or release.