Oxidative stress markers in bipolar disorder: A meta-analysis

Ana C. Andreazza, Marcia Kauer-Sant'Anna, Benicio N. Frey, David J. Bond, Flavio Kapczinski, L. Trevor Young, Lakshmi N. Yatham

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416 Scopus citations


Background: Oxidative stress is thought to mediate neuropathological processes of a number of neuropsychiatric disorders and recent data suggest that oxidative stress may be involved in the pathophysiology of bipolar disorder (BD). In the present investigation, we conducted a meta-analysis of studies that evaluated markers of oxidative stress in individuals with BD, as compared to healthy controls. Methods: A Medline search was conducted to identify studies that measured peripheral markers of oxidative stress in bipolar disorder. Data were subjected to meta-analysis using a random effects model to examine the effect sizes of the pooled results. Bias assessment (Egger's test) and assessment of heterogeneity (I2) were also carried out. Results: Thiobarbituric acidic reactive substances (TBARS) (p = 0.001) as well as NO activity (p = 0.02) were significantly increased in BD with a large effect size for TBARS and a moderate effect size for increase in NO. No significant effect sizes were observed for the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (all p > 0.05). Limitations: Some caution is warranted in interpreting these results: (1) Egger's test was positive for SOD, suggesting that SOD results may have been influenced by a publication bias. (2) We analyzed the absolute values of each antioxidant enzyme separately and the literature suggests that an imbalance between the antioxidant enzymes is a better indication of the presence of oxidative stress. Conclusions: The present meta-analysis suggests that oxidative stress markers are increased in BD and that oxidative stress may play a role in the pathophysiology of BD.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalJournal of Affective Disorders
Issue number2-3
StatePublished - Dec 2008
Externally publishedYes

Bibliographical note

Funding Information:
The CNPq provided a scholarship to Ana Andreazza. No further funding for this study was providing by CNPq (Brazil). CNPq had no further role in study design; in the data collection, analysis and interpretation of data; in the writing of the report, and in the decision to submit the paper for publication.

Funding Information:
Dr. Andreazza has been supported by CNPq (Brazil).

Funding Information:
Dr. Kauer-Sant'Anna has been an investigator in clinical trials sponsored by Novartis, Servier, Canadian Institutes of Health Research, and Stanley Foundation and has received salary support from an APA / AstraZeneca unrestricted educational grant.

Funding Information:
Dr. Frey has been supported by the Canadian Institutes of Health Research.

Funding Information:
Dr. Kapczinski has been an investigator in clinical trials sponsored by CNPq, the Canadian Institutes of Health Research, Stanley Foundation and Servier. He has worked as a consultant/speaker for Servier, AstraZeneca, Eli Lilly and Abbott.

Funding Information:
Dr. Young has received research grants from: the Canadian Institutes of Health Research and Stanley Foundation and is a speaker for Eli Lilly and AstraZeneca.

Funding Information:
Dr. Yatham is on speaker/advisory boards for, or has received research grants from: AstraZeneca, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Eli Lilly, GlaxoSmithKline, Janssen, Michael Smith Foundation for Health Research, Pfizer, Servier and Stanley Foundation.

Funding Information:
We thank the CNPq for providing the scholarship to Ana Andreazza.

Copyright 2009 Elsevier B.V., All rights reserved.


  • Antioxidants enzymes
  • Bipolar disorder
  • Lipid peroxidation
  • Meta-analysis
  • Nitric oxide
  • Oxidative stress


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