Schizophrenia:: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo
Schizophrenia:: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo
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DOI：
10.1046/j.1460-9568.2000.00229.x
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发表时间：
2000-10-01
影响因子：
3.4
通讯作者：
Cuénod, M
中科院分区：
文献类型：
--
作者：
Do, KQ;Trabesinger, AH;Cuénod, M
精神分裂症是一种严重的精神疾病，它影响人格的中心，具有感知、认知以及情感和社会行为的严重问题。在无药物精神分裂症患者的脑脊液中，与对照组相比，观察到总谷胱甘肽（GSH）水平显著降低27% (P < 0.05)，与其报道的代谢物γ -谷氨酰谷氨酰胺水平降低保持一致。采用新的无创质子磁共振波谱方法，发现精神分裂症患者内侧前额叶皮层GSH水平比对照组低52% （P = 0.0012）。谷胱甘肽在保护细胞免受多巴胺代谢产生的活性氧损伤方面起着重要作用。谷胱甘肽的缺失会导致多巴胺能末梢周围的退行性过程，从而导致连通性的丧失。谷胱甘肽还能增强n -甲基- d -天冬氨酸（NMDA）受体对谷氨酸的反应，这种作用可能因谷胱甘肽缺乏而减弱，导致类似于苯环利定（PCP）的应用。因此，谷胱甘肽假说可能整合了精神分裂症的许多已确立的生物学方面。
Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P < 0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.