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Kelvin O. Lim, MD; Elfar Adalsteinsson, PhD; Daniel Spielman, PhD; Edith V. Sullivan, PhD; Margaret J. Rosenbloom, MA; Adolf Pfefferbaum, MD

Arch Gen Psychiatry. 1998;55:346-352.

Objective  To apply in vivo proton magnetic resonance spectroscopy imaging estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative contribution of neuronal and glial changes to the widespread volume deficit of cortical gray matter seen in patients with schizophrenia with magnetic resonance images.

Methods  Ten male veterans meeting criteria of the DSM-IV, for schizophrenia and 9 healthy age-matched men for comparison were scanned using spectroscopic, anatomical, and field-map sequences. Instrument and collection variables were standardized to allow an estimation of comparable values for NAA, choline, and creatine for all subjects. Metabolite values from each voxel on 3 upper cortical slices were regressed against the gray tissue proportion of that voxel to derive estimates of gray and white matter NAA, creatine, and choline concentrations.

Results  The volume of cortical gray matter was reduced in patients with schizophrenia, but NAA signal intensity from a comparable region was normal. In contrast, the volume of cortical white matter was normal in patients with schizophrenia, but NAA signal intensity from a comparable region was reduced.

Conclusions  The lack of reduction in gray matter NAA signal intensity suggests that the cortical gray matter deficit in these patients involved both neuronal and glial compartments rather than a neurodegenerative process in which there is a decrease in the neuronal relative to the glial compartment. Reduced white matter NAA signal intensity without a white matter volume deficit may reflect abnormal axonal connections.

From the Psychiatry Service, Veterans Affairs Palo Alto Health Care System, Palo Alto (Dr Lim); the Department of Psychiatry and Behavioral Sciences (Drs Lim, Sullivan, and Pfefferbaum and Ms Rosenbloom) and the Department of Diagnostic Radiology (Drs Adalsteinsson and Spielman), Stanford University School of Medicine, Stanford; and the Neuropsychiatry Program, SRI International, Menlo Park (Drs Sullivan and Pfefferbaum), Calif. Dr Lim is now with the Division of Medical Physics, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY.

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