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Absence of Neurodegeneration and Neural Injury in the Cerebral Cortex in a Sample of Elderly Patients With Schizophrenia
Steven E. Arnold, MD;
John Q. Trojanowski, MD, PhD;
Raquel E. Gur, MD, PhD;
Peter Blackwell;
Li-Ying Han, MS;
Catherine Choi
Arch Gen Psychiatry. 1998;55:225-232.
Background The cognitive and functional deterioration that is observed in many "poor-outcome" patients with schizophrenia suggests a neurodegenerative process extending into late life. Previous diagnostic studies have excluded known neurodegenerative diseases as explanations for this dementia. However, we hypothesized that relatively small accumulations of age- or disease-related neurodegenerative lesions occurring in an otherwise abnormal brain could result in deterioration in schizophrenia.
Methods Postmortem studies were conducted using 23 prospectively accrued elderly persons with chronic schizophrenia for whom clinical ratings had been determined before death, 14 elderly control patients with no neuropsychiatric disease, and 10 control patients with Alzheimer disease. Immunohistochemistry and unbiased stereological counting methods were used to quantify common neurodegenerative lesions (ie, neurofibrillary tangles, amyloid plaques, and Lewy bodies) and cellular reactions to a variety of noxious stimuli (ubiquitinated dystrophic neurites, astrocytosis, and microglial infiltrates) in the ventromedial temporal lobe and the frontal and the calcarine (primary visual) cortices.
Results No statistically significant differences were found between the patients with schizophrenia and the control patients without neuropsychiatric disease for the densities of any of the markers, while both groups exhibited fewer lesions than did the control group with Alzheimer disease. Correlation analyses in the schizophrenia sample failed to identify significant correlations between cognitive and psychiatric ratings and densities of any of the neuropathologic markers.
Conclusions No significant evidence of neurodegeneration or ongoing neural injury in the cerebral cortex was found in this sample of elderly persons with schizophrenia. Furthermore, the behavioral and cognitive deterioration observed in late life did not correlate with age-related degenerative phenomena.
From the Departments of Psychiatry (Drs Arnold and Gur, Mr Blackwell, and Mss Han and Choi), Neurology (Drs Arnold and Gur), and Pathology and Laboratory Medicine (Dr Trojanowski), University of Pennsylvania School of Medicine, Philadelphia.
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