165. Nature of Glutamate Alterations in Schizophrenia: A Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies

Abstract

Background: Alterations in glutamatergic neurotransmission may be fundamental to the pathophysiology of schizophrenia and the glutamatergic system may be a target for new therapeutic interventions. To investigate the nature of brain glutamate alterations in schizophrenia we present a meta-analysis of glutamate proton magnetic resonance (1H-MRS) studies. Methods: Electronic databases were searched to identify journal articles reporting 1H-MRS glutamate, its metabolite glutamine or Glx (total glutamate+glutamine) in schizophrenia patients in comparison to healthy volunteers. Effect sizes were calculated for glutamate, glutamine and Glx in brain regions reported in at least 3 studies. Secondary analysis grouped studies into those examining different illness stages (high risk, first-episode psychosis or chronic schizophrenia). Results: 59 eligible studies were identified. In schizophrenia, there were significant elevations in glutamate in the basal ganglia (P = .01, g = 0.63), glutamine in the thalamus (P = .04, g = 0.56), and Glx in the basal ganglia (P = .01, g = .39) and medial temporal lobe (P = .002, g = .32). No region showed a reduction in glutamate metabolites in schizophrenia. Sufficient studies were available to show that these glutamatergic elevations were present at different illness stages; Glx and glutamine elevations in the medial frontal cortex were specific to high-risk and first-episode patients respectively, whereas Glx elevations in medial temporal lobe were specific to patients with chronic schizophrenia. Conclusion: Schizophrenia is associated with elevations in glutamatergic metabolites across several brain regions. This supports the hypothesis that schizophrenia is associated with excess glutamatergic neurotransmission in several limbic areas, and further indicates that compounds that reduce glutamatergic transmission may have therapeutic potential.