Magnetic resonance spectroscopy studies in schizophrenia

Abstract

MRS is a neuroimaging modality that provides information on brain biochemistry and microstructure. Research in schizophrenia using this modality is rapidly growing and meaningful insights have already been obtained. This chapter highlights both methodological and interpretation challenges for MRS research, and reviews the progress that has been made, with a particular focus on metabolites measured using proton and phosphorus MRS. This literature indicates that N-acetylaspartate concentrations are reduced in schizophrenia, reflecting abnormal neuronal integrity and function. This neuronal signal abnormality may be related to another major finding in MRS studies, and that is elevated glutamate-related metabolite signals. Elevated glutamate signaling is consistent with hypofunction of the NMDA receptor, which has been hypothesized in schizophrenia and which may give rise to downstream neuronal dysfunction. A separate line of research has identified deficient ATP production in schizophrenia, which may reflect reduced oxidative phosphorylation and a compensatory shift towards glycolysis. These bioenergetic abnormalities are also accompanied by redox imbalance, reflected in the NAD+/NADH ratio. Taken together, these findings are consistent with mitochondrial dysfunction in schizophrenia. This picture would be expected to impair information processing because brain activity is energetically expensive and reductions in energy supply are known to dysregulate neuronal function. MRS research has contributed insights into the biochemical correlates of schizophrenia and it is expected to play an even greater role in the future of our field due to ongoing technical improvements and higher magnet strengths.