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Schizophrenia Bulletin 1998 24(3):365-379;
© 1998 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
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© Oxford University Press

Heterogeneity of the Psychoses: Is There a Neurodegenerative Psychosis?

James L. Knoll, IV, M.D., David L. Garver, M.D., Jane E. Ramberg, M.S., Steven J. Kingsbury, M.D., Ph.D., Deborah Croissant, M.S., B.S.N. and Barbara McDermott, Ph.D.
Psychiatry Resident, Southwestern Medical Center, University of Texas Dallas, TX
Communities Foundation Trust Professor of Brain Science, Southwestern Medical Center, University of Texas Dallas TX, Director of Research, Mental Health, Dallas Veterans Affairs Medical Center (VAMC), Director, National Clozapine Coordinating Center, Dallas VAMC, and Staff Physician, Dallas VAMC Dallas, TX
Research Assistant, Dallas VAMC
Staff Psychiatrist/Psychologist, Dallas VAMC, and Assistant Professor in the Departments of Psychiatry and Psychology, Southwestern Medical Center, University of Texas Dallas, TX
Research Assistant, Southwestern Medical Center, University of Texas Dallas, TX
Associate Professor of Psychiatry and Neurology, Department of Psychiatry and Neurology, Tulane University Medical School New Orleans, LA

Reprint requests should be sent to Dr. D.L. Garver, Dallas VA Medical Center (116A), 4500 S. Lancaster Rd., Dallas, TX 75216

Whereas etiological heterogeneity of the various types of schizophrenia has been repeatedly proposed, relatively few attempts have been made to separate the component diseases. Using a strategy focusing on bimodal distributions within several relevant domains of schizophrenia, we demonstrate that currently available data on schizophrenia patients are consistent with the hypothesis that some of these patients have an ongoing neurodegenerative disease, whereas others do not. We review studies (longitudinal and cross-sectional) documenting progressive increases in ventricular size, accelerated loss of brain tissues, progressive delays in treatment response, and neurochemical (magnetic resonance spectroscopy) and neurophysiological (P300) indices, all of which are consistent with ongoing cerebral degeneration in a significant subgroup of schizophrenia patients. These lines of evidence converge on a conceptualization of schizophrenia as being composed of several etiologically distinct processes, with one subset of psychotic patients evidencing progressive brain degeneration. We conclude with a discussion of possible etiologies for this condition.

Keywords: Heterogeneity / ventricular brain ratio / phosphoesters / evoked cortical response / degeneration / apoptosis / drug response


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