Is depression associated with increased oxidative stress? A systematic review and meta-analysis
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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.
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Depression is accompanied by observation of oxidative DNA damage, namely 8-OH-Gua confirmed by analysis of plasma, urine, and leucocytes of patients with depression.
“Depression is accompanied by observation of oxidative DNA damage, namely 8-OH-Gua (see above) confirmed by the analysis of plasma, urine, and leucocytes of patients with depression (Black et al. 2015).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Black et al. 2015
Increased oxidative damage occurs quite often in depression.
“increased oxidative damage occurs quite often in depression [7–9]”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [8]
Both 8-hydroxy-2-deoxyguanosine and F2-isoprostanes are increased in depression.
“Black et al. in 2015 [8] revealed that both 8-hydroxy-2-deoxyguanosine (8-OHdG) and F2-isoprostanes are increased in depression”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [8]
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- Authors
- Black, C. N., Bot, M., Scheffer, P. G., Cuijpers, P., & Penninx, B. W. J. H.
- Affiliations
- Amsterdam Public Health (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Black, Catherine N.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 51
- Pages
- 164-175
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2120423982
- Cited by
- 711
- References
- 80
- Citations by year
- 2026: 38 · 2025: 61 · 2024: 70 · 2023: 74 · 2022: 89 · 2021: 106 · 2020: 85 · 2019: 67 · 2018: 36 · 2017: 41 · 2016: 26 · 2015: 16 · 2014: 1
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Vanderbilt University
- Northwestern University
- University of Minnesota
- National Center for Global Health and Medicine
- Vanderbilt University Medical Center
- Vrije Universiteit Amsterdam
- GGZ inGeest
- University of California, San Francisco
- Walter H. Shorenstein Asia-Pacific Research Center
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, oxidative stress, 8-hydroxy-2'-deoxyguanosine, F2-isoprostanes, oxidative DNA damage, lipid peroxidation, major depressive disorder, bipolar disorder, antioxidant defense, oxidative stress biomarkers
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Bipolar Disorder, Deoxyguanosine, Depression, Major Depressive Disorder, Humans, Biomarkers, Oxidative Stress, F2-Isoprostanes
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