Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia

Bipolar Disord. 2009 Aug;11(5):523-9. doi: 10.1111/j.1399-5618.2009.00717.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Analysis of Variance
  • Bipolar Disorder / pathology*
  • Case-Control Studies
  • Depressive Disorder, Major / pathology
  • Female
  • Gyrus Cinguli / physiopathology*
  • Humans
  • Lipid Peroxidation / physiology
  • Male
  • Oxidative Stress / physiology*
  • Postmortem Changes
  • Schizophrenia / pathology*
  • Statistics as Topic


  • Aldehydes
  • 4-hydroxy-2-nonenal