Arnold S E, Trojanowski J Q, Gur R E, Blackwell P, Han L Y, Choi C
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Arch Gen Psychiatry. 1998 Mar;55(3):225-32. doi: 10.1001/archpsyc.55.3.225.
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.
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.
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.
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.
在许多“预后不良”的精神分裂症患者中观察到的认知和功能衰退表明存在一种延伸至晚年的神经退行性过程。先前的诊断研究已排除已知的神经退行性疾病作为这种痴呆症的病因。然而，我们推测在原本异常的大脑中出现的与年龄或疾病相关的相对较小的神经退行性病变积累可能导致精神分裂症患者的病情恶化。
对23例生前已确定临床评分的前瞻性招募的老年慢性精神分裂症患者、14例无神经精神疾病的老年对照患者和10例阿尔茨海默病对照患者进行了尸检研究。采用免疫组织化学和无偏立体计数方法，对腹内侧颞叶、额叶和距状（初级视觉）皮质中的常见神经退行性病变（即神经原纤维缠结、淀粉样斑块和路易体）以及对各种有害刺激的细胞反应（泛素化营养不良性神经突、星形细胞增生和小胶质细胞浸润）进行定量分析。
精神分裂症患者与无神经精神疾病的对照患者在任何标志物的密度上均未发现统计学上的显著差异，而两组的病变均少于阿尔茨海默病对照患者组。对精神分裂症样本的相关性分析未能确定认知和精神评分与任何神经病理学标志物密度之间的显著相关性。
在这个老年精神分裂症患者样本中，未发现大脑皮质神经退行性变或持续神经损伤的显著证据。此外，晚年观察到的行为和认知衰退与年龄相关的退行性现象无关。
