Measurements of W-Acetyl-Aspartate (NAA) with magnetic resonance proton spectroscopy (MRS) have contributed important clues to the arduous discovery of the pathophysiology of schizophrenia. In this chapter, we will describe the findings that have emerged from the Clinical Brain Disorders Branch of the NIMH over the last decade or so and try to give a critical context to the literature in this field. Given the space limitations and the vast literature available on MRS, the citation list will be far from exhaustive. Comprehensive reviews of NAA measures in schizophrenia have appeared elsewhere.1-5 The findings will be articulated in three main threads: 1) evidence that measures of NAA index cortical changes in schizophrenia; 2) the changes shown in MRS studies converge with the information provided by other measurement modalities such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), indicating that NAA concentrations predict the function of distributed cortical circuitry in schizophrenia; 3) variation in genes that are associated with increased risk for schizophrenia is also associated with changes in NAA concentrations, offering for the first time a window on the molecular mechanisms underlying reduction of NAA and the pathophysiology of schizophrenia.

Genes, Cognition and Psychosis Program, Division of Intramural Research, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland USA. Correspondence to D.R Weinberger, 10 Center Drive, Rm. 4S-235, Bethesda, Maryland 20892, email: [email protected].

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