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Depression and Oxidative Stress: Results From a Meta-Analysis of Observational Studies

Palta, Priya PhD, MHS; Samuel, Laura J. PhD, MSN; Miller, Edgar R. III PhD, MD; Szanton, Sarah L. PhD, CRNP

doi: 10.1097/PSY.0000000000000009
Systematic Review/Meta-Analysis

Objective To perform a systematic review and meta-analysis that quantitatively tests and summarizes the hypothesis that depression results in elevated oxidative stress and lower antioxidant levels.

Methods We performed a meta-analysis of studies that reported an association between depression and oxidative stress and/or antioxidant status markers. PubMed and EMBASE databases were searched for articles published from January 1980 through December 2012. A random-effects model, weighted by inverse variance, was performed to pool standard deviation (Cohen’s d) effect size estimates across studies for oxidative stress and antioxidant status measures, separately.

Results Twenty-three studies with 4980 participants were included in the meta-analysis. Depression was most commonly measured using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. A Cohen’s d effect size of 0.55 (95% confidence interval = 0.47–0.63) was found for the association between depression and oxidative stress, indicating a roughly 0.55 of 1-standard-deviation increase in oxidative stress among individuals with depression compared with those without depression. The results of the studies displayed significant heterogeneity (I2 = 80.0%, p < .001). A statistically significant effect was also observed for the association between depression and antioxidant status markers (Cohen’s d = −0.24, 95% confidence interval = −0.33 to −0.15).

Conclusions This meta-analysis observed an association between depression and oxidative stress and antioxidant status across many different studies. Differences in measures of depression and markers of oxidative stress and antioxidant status markers could account for the observed heterogeneity. These findings suggest that well-established associations between depression and poor heath outcomes may be mediated by high oxidative stress.

From the Department of Epidemiology (P.P., L.J.S., E.R.M.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Department of Epidemiology (P.P), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Johns Hopkins University School of Nursing (S.L.S.), Baltimore, Maryland; and Department of General Internal Medicine (E.R.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address correspondence and reprint requests to Priya Palta, PhD, MHS, University of North Carolina at Chapel Hill, 137 E. Franklin Street, Suite 306, Chapel Hill, NC 27514. E-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

Received for publication August 17, 2012; revision received September 7, 2013.

Copyright © 2014 by American Psychosomatic Society
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