What have we learned from proton magnetic resonance spectroscopy about schizophrenia? A critical update

Purpose of review This review discusses recent studies investigating schizophrenia with proton magnetic resonance spectroscopy including the first meta-analysis [Steen RG, Hamer RM, Lieberman X Measurement of brain metabolites by 1 H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychology 2005; 30:1949-1962]. We also highlight methodological issues and suggest a modality for future research to further explore glutamatergic dysfunction in schizophrenia. Recent findings Despite methodological differences, spectroscopy studies with schizophrenia show reductions in N-acetylaspartate in the medial temporal and prefrontal regions. Other areas such as the anterior cingulate, parietal cortex thalamus, and cerebellum may also have N-acetylaspartate reductions. The proton magnetic resonance spectroscopy studies at higher fields and with shorter echo time have revealed abnormalities in glutamate and glutamine. Animal studies have shown that the discrepancies in metabolites between patients and controls are not due to antipsychotic medication exposure, and that chronic exposure to N-methyl-D-aspartate antagonists has produced decreased N-acetylaspartate in the temporal cortex. The human and animal studies both support an excitoxic glutamatergically mediated process that may explain decreased N-acetylaspartate, volume loss, and the poor outcomes of schizophrenia. Summary Use of higher field strengths and longitudinal studies may reveal a progressive excitoxic glutamatergic process that leads to N-acetylaspartate and volume reductions. This may lead to the development of neuroprotective agents that change the course of schizophrenia.