Is depression associated with increased oxidative stress? A systematic review and meta-analysis

Background: It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes, measures of oxidative DNA and lipid damage respectively, are among the most reliable oxidative stress markers, but studies on their association with depression show conflicting results. This meta-analysis quantifies the association between depression and these markers and explores factors that may explain inconsistencies in the results. Methods: A systematic literature search was conducted in PubMed, EMBASE and PsycINFO. Studies assessing the association of 8-OHdG or F2-isoprostanes with elevated depressive symptoms, major depressive disorder (MDD) or bipolar disorder (BD) were pooled in two random-effect models. Results: The pooled effect size (Hedges' g) for the association of depression with oxidative stress was 0.31 (p = 0.01, I-2 = 75%) for 8-OHdG (10 studies, 1308 subjects) and 0.48 (p = 0.001, I-2 = 73%) for F2-isoprostanes (8 studies, 2471 subjects), indicating that both markers are increased in depression. There was no indication of publication bias for either marker. The F2-isoprostane results did not differ by type of depression, biological specimen, laboratory method or quality, however subgroup analyses in the 8-OHdG studies showed significantly stronger associations in plasma/serum vs. urine samples (p < 0.01), in measurements performed with immuno-assay vs. chromatography mass spectrometry (p < 0.01) and weaker associations in high quality studies vs. low (p = 0.02). Conclusion: This meta-analysis finds that oxidative stress, as measured by 8-OHdG and F2-isoprostanes, is increased in depression. Larger-scale studies are needed to extend the evidence on oxidative stress in depression, and examine the potential impact of treatment. (C) 2014 Elsevier Ltd. All rights reserved.