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The Journal of Neuroscience, May 1, 2002, 22(9):3720-3729

Genetic Contributions to Altered Callosal Morphology in Schizophrenia

Katherine L. Narr^{1, 3}, Tyrone D. Cannon⁴, Roger P. Woods^{2, 3}, Paul M. Thompson^{1, 3}, Sharon Kim^{1, 3}, Dina Asunction^{1, 3}, Theo G. M. van Erp⁴, Veli-Pekka Poutanen⁶, Matti Huttunen⁷, Jouko Lönnqvist⁷, Carl-Gustav Standerksjöld-Nordenstam⁶, Jaakko Kaprio^{7, 8}, John C. Mazziotta^{2, 3, 5}, and Arthur W. Toga^{1, 2, 3}

¹ Laboratory of Neuro Imaging, ² Ahmanson-Lovelace Brain Mapping Center, Neuropsychiatric Institute, ³ Department of Neurology, ⁴ Departments of Psychology, Psychiatry, and Human Genetics, and ⁵ Departments of Radiology and Pharmacology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1769, ⁶ Department of Radiology, Helsinki University Central Hospital, Meilahti Clinics, FIN-00290 Helsinki, Finland, ⁷ Department of Mental Health and Alcohol Research, National Public Health Institute of Finland, SF-0030 Helsinki, Finland, and ⁸ Department of Public Health, University of Helsinki, FIN-0014 Helsinki, Finland

Patients with schizophrenia exhibit abnormalities in midsagittal corpus callosum area, shape, and/or displacement. Our goal was to confirm these findings and to establish the genetic and nongenetic contributions to altered callosal morphology in schizophrenia. Relationships between ventricular enlargements potentially contributing to callosal displacements were assessed as a secondary goal. High-resolution magnetic resonance images were obtained from co-twins of monozygotic and dizygotic pairs discordant for schizophrenia and healthy control twins (N = 40 pairs). Investigators blind to group status segmented the corpus callosum and ventricles in native brain volumes aligned using a rigid-body transformation with no scaling. Total and parcellated midsagittal callosal areas and measures indexing vertical displacements of the corpus callosum were used in statistical tests to identify schizophrenia and sex effects and to dissociate genetic and nongenetic influences on morphology. Anatomical mesh modeling methods provided group average and surface variability maps of the callosum. Callosal areas did not differ between groups defined by sex or biological risk. Vertical displacements of the callosum, pronounced in male patients, were confirmed in schizophrenia and observed between dizygotic, but not monozygotic co-twins discordant for schizophrenia. Like their affected twins, however, unaffected monozygotic co-twins of the schizophrenia probands exhibited significant callosal displacements. Lateral and third ventricle enlargements were related to callosal displacements. Results clearly support that genetic rather than disease-specific or shared environmental influences contribute to altered callosal morphology in schizophrenia. An upward bowing of the callosum may thus provide an easily identifiable neuroanatomic marker to screen individuals possessing a biological vulnerability for schizophrenia.

Key words: corpus callosum morphology; schizophrenia; genetic effects; environmental effects; monozygotic twins; dizygotic twins; morphology; imaging

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2293720-10$05.00/0

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