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Gina R. Kuperberg, MD, PhD, MRCPsych; Matthew R. Broome, MB, ChB, MRCPsych; Philip K. McGuire, MD, PhD, MRCPsych; Anthony S. David, MD, FRCPsych; Marianna Eddy, BA; Fujiro Ozawa, MD, PhD; Donald Goff, MD; W. Caroline West, PhD; Steven C. R. Williams, PhD; Andre J. W. van der Kouwe, PhD; David H. Salat, PhD; Anders M. Dale, PhD; Bruce Fischl, PhD

Arch Gen Psychiatry. 2003;60:878-888.

Background  Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps.

Methods  Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon.

Results  Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels.

Conclusions  Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.

From the Department of Psychiatry, Massachusetts General Hospital (Drs Kuperberg and Goff), and the Athinoula A. Martinos Center for Biomedical Imaging (Drs Kuperberg, Ozawa, van der Kouwe, Salat, Dale, and Fischl), Charlestown, Mass; the Section of Neuroimaging, Division of Psychological Medicine (Drs Broome, McGuire, and David), and the Department of Neurology (Dr Williams), Institute of Psychiatry, London, England; and the Department of Neurology, Massachusetts General Hosital, Boston (Ms Eddy and Dr West).

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