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Aaron L. Goldman, BSc; Lukas Pezawas, Priv Doz, Dr; Venkata S. Mattay, MD; Bruce Fischl, PhD; Beth A. Verchinski, BS; Qiang Chen, PhD; Daniel R. Weinberger, MD; Andreas Meyer-Lindenberg, MD, PhD

Arch Gen Psychiatry. 2009;66(5):467-477.

Context  Schizophrenia is a brain disorder with predominantly genetic risk factors, and previous research has identified heritable cortical and subcortical reductions in local brain volume. To our knowledge, cortical thickness, a measure of particular interest in schizophrenia, has not previously been evaluated in terms of its heritability in relationship to risk for schizophrenia.

Objective  To quantify the distribution and heritability of cortical thickness changes in schizophrenia.

Design  We analyzed a large sample of normal controls, affected patients, and unaffected siblings using a surface-based approach. Cortical thickness was compared between diagnosis groups on a surfacewide node-by-node basis. Heritability related to disease risk was assessed in regions derived from an automated cortical parcellation algorithm by calculating the Risch .

Setting  Research hospital.

Participants  One hundred ninety-six normal controls, 115 affected patients with schizophrenia, and 192 unaffected siblings.

Main Outcome Measure  Regional cortical thickness.

Results  Node-by-node mapping statistics revealed widespread thickness reductions in the patient group, most pronouncedly in the frontal lobe and temporal cortex. Unaffected siblings did not significantly differ from normal controls at the chosen conservative threshold. Risch analysis revealed widespread evidence for heritability for cortical thickness reductions throughout the brain.

Conclusions  To our knowledge, the present study provides the first evidence of broadly distributed and heritable reductions of cortical thickness alterations in schizophrenia. However, since only trend-level reductions of thickness were observed in siblings, cortical thickness per se (at least as measured by this approach) is not a strong intermediate phenotype for schizophrenia.

Author Affiliations: Neuroimaging Core Facility, Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Mr Goldman, Drs Pezawas, Mattay, Chen, Weinberger, and Meyer-Lindenberg, and Ms Verchinski); Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center, Harvard Medical School, Charlestown, and Department of Health Sciences and Technology and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge (Dr Fischl); and Central Institute of Mental Health, Mannheim, Germany (Dr Meyer-Lindenberg). Dr Pezawas is now with the Division of Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.

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