A Meta-Analysis of Oxidative Stress Markers in Depression

PLoS One. 2015 Oct 7;10(10):e0138904. doi: 10.1371/journal.pone.0138904. eCollection 2015.


Object: Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis aims to analyse the clinical data quantitatively by comparing the oxidative stress markers between depressed patients and healthy controls.

Methods: A search was conducted to collect the studies that measured the oxidative stress markers in depressed patients. Studies were searched in Embase, Medline, PsychINFO, Science direct, CBMDisc, CNKI and VIP from 1990 to May 2015. Data were subjected to meta-analysis by using a random effects model for examining the effect sizes of the results. Bias assessments, heterogeneity assessments and sensitivity analyses were also conducted.

Results: 115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin, high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy (p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were no differences between the depressed patients and controls for other oxidative stress markers.

Conclusion: This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication. The pathophysiological relationships between oxidative stress and depression, and the potential benefits of antioxidant supplementation deserve further research.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism
  • Antidepressive Agents / therapeutic use
  • Antioxidants / metabolism
  • Aryldialkylphosphatase / blood
  • Ascorbic Acid / blood
  • Biomarkers / blood*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Depression / blood*
  • Depression / drug therapy
  • Depression / metabolism
  • Depressive Disorder / blood*
  • Depressive Disorder / drug therapy
  • Depressive Disorder / metabolism
  • F2-Isoprostanes / blood
  • Humans
  • Lipid Peroxidation / drug effects
  • Lipoproteins, HDL / blood
  • Malondialdehyde / blood
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Uric Acid / blood


  • Albumins
  • Antidepressive Agents
  • Antioxidants
  • Biomarkers
  • F2-Isoprostanes
  • Lipoproteins, HDL
  • Uric Acid
  • Malondialdehyde
  • Aryldialkylphosphatase
  • Ascorbic Acid

Grant support

This work was supported by grants from the Planned Science and Technology Project of Guangdong Province, China (No:2014A020212401, 2014B020212022), the Educational Commission of Guangdong Province, China (No: 2013KJCX0025), the Humanities and Social Sciences Planning Fund (No:13YJA190008) and the Scientific Cultivation and Innovation Fund of Jinan University (No:21615466). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.