Oxidative stress markers in bipolar disorder: a meta-analysis.
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 (I(2)) 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).


CONCLUSIONS
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.
Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
Ana C
AC
Andreazza
Marcia
M
Kauer-Sant'anna
Benicio N
BN
Frey
David J
DJ
Bond
Flavio
F
Kapczinski
L Trevor
LT
Young
Lakshmi N
LN
Yatham
D000975:Antioxidants / Q000378:metabolism / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D035061:Control Groups; D004912:Erythrocytes / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D050050:Protein Carbonylation / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase