The pathological process of bipolar disorder and schizophrenia may be due, in part, to oxidative damage, say Canadian researchers in findings that may point to novel treatment approaches.

There is increasing evidence to suggest that mitochondrial dysfunction is present in the brains of bipolar disorder patients. Furthermore, the mitochondrial electron transport chain is a major source of reactive oxygen species, which cause oxidative stress.

To examine associations between bipolar disorder and oxidative stress, Jun-Feng Wang and colleagues from the University of British Columbia in Vancouver studied postmortem anterior cingulate brain sections from 15 bipolar disorder patients, 15 major depressive disorder (MDD), patients, 15 schizophrenia patients, and 15 controls matched for age, gender, postmortem interval (PMI), pH, and messenger RNA quality.

As a surrogate for oxidative stress, levels of 4-hydroxynonenal (4-HNE), which s a major product of lipid peroxidation, were determined via immunohistochemical analysis of 4-HNE protein adducts.

Compared with controls, 4-HNE levels were significantly increased in bipolar disorder and schizophrenia patients by 59% and 47%, respectively. Although levels were 33% higher in MDD patients than in controls, the difference was not significant.

Studying medication-free patients only, the team found that 4-HNE levels were increased significantly compared with controls in both bipolar disorder and schizophrenia patients, at 94% and 72%, respectively, with no change recorded in MDD patients.

Four-HNE levels were unaffected by age, gender, and PMI. In all brain samples, 4-HNE levels were negatively correlated with pH, the team says in the journal Bipolar Disorders.

However, 4-HNE levels were still significantly increased in bipolar disorder patients and there was a trend for an increase in schizophrenia patients when pH was used as a covariate. In addition, 4-HNE levels were negatively correlated with pH only in bipolar disorder patients.

“Oxidative damage in the brain may contribute to the pathological process of bipolar disorder and schizophrenia, and anti-oxidative stress may well serve as an alternative approach to pharmacological treatment of these psychiatric disorders, the researchers conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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