Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia.
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.
Wang
Jun-Feng
JF
Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. junfengw@exchange.ubc.ca
Shao
Li
L
Sun
Xiujun
X
Young
L Trevor
LT
D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000473:pathology*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000473:pathology; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D011180:Postmortem Changes; D012559:Schizophrenia / Q000473:pathology*; D013223:Statistics as Topic
D000447:Aldehydes; C027576:4-hydroxy-2-nonenal