期刊
BIPOLAR DISORDERS
卷 11, 期 5, 页码 523-529出版社
WILEY
DOI: 10.1111/j.1399-5618.2009.00717.x
关键词
4-hydroxynonenal; bipolar disorder; lipid peroxidation; mitochondrial dysfunction; postmortem cingulate cortex
资金
- Canadian Institutes of Health Research
Background: Recent studies indicate the presence of mitochondrial dysfunction in brains of subjects with bipolar disorder (BD). Because the mitochondrial electron transport chain is a major source for production of reactive oxygen species that cause oxidative stress, we sought to determine in the present study if BD is associated with oxidative stress. Methods: Postmortem anterior cingulate brain sections from subjects with BD, major depressive disorder (MDD), or schizophrenia, and from nonpsychiatric, non-neurologic comparison controls were generously provided by the Stanley Foundation Neuropathology Consortium. Oxidative stress was determined by analyzing 4-hydroxynonenal (4-HNE), a major product of lipid peroxidation. The level of 4-HNE was determined by measuring 4-HNE protein adducts using immunohistochemistry. Results: We found that 4-HNE levels were significantly increased by 59% in BD subjects and by 47% in schizophrenia subjects, but not in MDD subjects, when compared with controls. Levels of 4-HNE were negatively correlated with pH in all 60 subjects. When pH was used as covariate, 4-HNE levels were still significantly increased in BD subjects when compared with controls. Further, 4-HNE levels were significantly correlated with pH values only in BD subjects, but not in MDD, schizophrenia, or control subjects. Conclusions: Oxidative damage in the brain may contribute in part to the pathological process in BD and schizophrenia. This finding also suggests antioxidative stress as a probable alternative approach to the pharmacological treatment of these psychiatric disorders.
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