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Schizophrenia Bulletin 2003 29(4):803-830;
© 2003 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
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© Oxford University Press

A Review and New Report of Medial Temporal Lobe Dysfunction as a Vulnerability Indicator for Schizophrenia: A Magnetic Resonance Imaging Morphometric Family Study of the Parahippocampal Gyrus

Larry J. Seidman, Ph.D., Christos Pantelis, MRCPsych, FRANZCP, Matcheri S. Keshavan, M.D., Stephen V. Faraone, Ph.D., Jill M. Goldstein, Ph.D., Nicholas J. Horton, Sc.D., Nikos Makris, M.D., Ph.D., Falkai Peter, M.D., Verne S. Caviness, M.D., D.Phil and Ming T. Tsuang, M.D., Ph.D.
Associate Professor of Psychology and Director, Commonwealth Research Center, Harvard Medical School Department of Psychiatry at Massachusetts Mental Health Center Boston, MA; Harvard Medical School Department of Psychiatry at Brockton/West Roxbury VA Medical Center Brockton, MA; Harvard Medical School Department of Psychiatry at Massachusetts General Hospital; Harvard Institute of Psychiatric Epidemiology and Genetics Boston, MA
Associate Professor of Psychiatry and Head, Cognitive Neuropsychiatry Research and Academic Unit, University of Melbourne, Sunshine Hospital St. Albans, Victoria, Australia
Professor of Psychiatry, Department of Psychiatry, UPMC Health System-Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine Pittsburgh, PA
Clinical Professor of Psychiatry, Harvard Medical School Department of Psychiatry at Massachusetts General Hospital; Professor in the Department of Epidemiology, Harvard School of Public Health Boston, MA.
Associate Professor of Psychiatry, Harvard Medical School Department of Psychiatry Brigham and Women's Hospital; Director of Research, Connors Center for Women's Health and Gender Biology Brigham and Women's Hospital Division of Women's Health; Harvard Medical School Department of Psychiatry at Massachusetts Mental Health Center; Harvard Medical School Department of Psychiatry at Massachusetts General Hospital Boston, MA
Assistant Professor, Smith College, Department of Mathematics Northampton, MA
Assistant Professor, Harvard Medical School Department of Neurology and Co-Director, Center for Morphometric Analysis, Massachusetts General Hospital Boston, MA
Professor, Harvard Medical School Department of Neurology and Director, Center for Morphometric Analysis, Massachusetts General Hospital Boston, MA
Professor of Psychiatry, Department of Psychiatry, University of Saarland Saarbrucken, Germany
University Professor and Director, Institute of Behavior Genomics, Department of Psychiatry, University of California San Diego, CA; Professor and Director, Harvard Institute of Psychiatric Epidemiology and Genetics, Department of Epidemiology, Harvard School of Public Health; Senior Lecturer, Harvard Medical School Department of Psychiatry at Massachusetts Mental Health Center Boston, MA

Send reprint requests to Dr. L.J. Seidman, Massachusetts Mental Health Center, Commonwealth Research Center, 170 Morton Street, Jamaica Plain, MA 02130-3735; e-mail: larry_seidman{at}hms.harvard.edu

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

Keywords: Schizophrenia / relatives / genetics / MRI / hippocampus / parahippocampal gyrus / verbal declarative memory


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