Abstract
The history of psychiatric research is filled with widely accepted etiologic and pathophysiologic
theories that eventually were proven wrong. The prevailing pathophysiologic theories
of schizophrenia have emphasized the role of abnormal neurodevelopment in determining
the onset and course of the illness. Relatively little attention has been paid to
the role of neurodegenerative processes despite the clinical course of the illness
and the fact that most patients experience varying degrees of behavioral and cognitive
deterioration. This is partially due to the absence of clear histologic evidence of
neurodegeneration, but may also be due to the narrow traditional conception of neurodegeneration
that is generally employed. This article suggests that the rejection of a role for
neurodegeneration in the pathophysiology of schizophrenia is unproven and may be premature.
A wholly neurodevelopmental perspective of the illness imbues the illness with a pessimistic
inevitability and therapeutic nihilism that may be unwarranted.
This article reviews selectively a diverse body of evidence that is consistent with
the hypothesis that schizophrenia involves a limited neurodegenerative process reflected
by the psychotic symptoms and that is most active in the early stages of the illness.
The evidence for this hypothesis comes from studies of premorbid status, illness course,
symptomatology and treatment effects as well as neuroimaging and postmortem findings.
Recent results from the latter interpreted in the context of molecular neurobiology
suggest new pathophysiologic models.
Keywords
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Article info
Publication history
Accepted:
June 7,
1999
Received in revised form:
May 18,
1999
Received:
May 12,
1998
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
