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Jill M. Goldstein, PhD; Julie M. Goodman, PhD; Larry J. Seidman, PhD; David N. Kennedy, PhD; Nikos Makris, MD, PhD; Hang Lee, PhD; Jason Tourville; Verne S. Caviness, Jr, MD, DPhil; Stephen V. Faraone, PhD; Ming T. Tsuang, MD, PhD

Arch Gen Psychiatry. 1999;56:537-547.

Background  Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls.

Methods  Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls.

Results  The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and fronto-orbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced.

Conclusion  Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions.

From the Department of Psychiatry (Drs Goldstein, Goodman, Seidman, Lee, Faraone, and Tsuang) and the Institute of Psychiatric Epidemiology and Genetics (Drs Goldstein, Seidman, Lee, Faraone, and Tsuang), Massachusetts Mental Health Center; the Departments of Neurology and Radiology Services, Center for Morphometric Analysis, Massachusetts General Hospital (Drs Goodman, Kennedy, Makris, and Caviness and Mr Tourville), Harvard Medical School; and the Department of Epidemiology, Harvard School of Public Health (Dr Tsuang), Boston; and the Department of Psychiatry, Harvard Medical School and Brockton–West Roxbury Veterans Affairs Medical Center (Drs Goldstein, Seidman, Faraone, and Tsuang), Brockton, Mass. Dr Lee is now at the Center for Vaccine Research, University of California–Los Angeles Medical Center.

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