Merritt K, McGuire PK, Egerton A, et al. - In proton magnetic resonance spectroscopy (1H-MRS) studies, an association of altered brain glutamatergic function has been reported with the pathophysiology of schizophrenia and the response to antipsychotic treatment. Researchers herein examined if clinical and demographic factors are linked with brain glutamate or glutamate plus glutamine (Glx) levels in schizophrenia. The MEDLINE database yielded 42 studies, with data for 1,251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1,197 healthy volunteers (mean [SD] age, 27.5 [8.8] years), for inclusion in this work. Per findings, patients exhibit lower medial frontal cortex glutamatergic metabolite levels and these levels negatively associate with the dose of antipsychotic medication, however, no acceleration in the reduction in glutamate levels with age was evident in patients with schizophrenia compared with healthy individuals. In patients with schizophrenia, more severe symptoms were observed to be linked with higher medial frontal cortex and medial temporal lobe glutamate levels. Hence, lower brain glutamate levels may be linked with antipsychotic exposure rather than with greater age-related reduction, whereas higher glutamate levels may indicate illness severity in these patients.