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Dysregulated relationship of inflammation and oxidative stress in major depression
Open accessAbstract
Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n=20) before and after 8 weeks of open-label sertraline treatment (n=17), compared to healthy non-depressed controls (n=20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p<0.05) and were negatively correlated with IL-10 concentrations (p<0.01). Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/IL-10 (p<0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio. After MDD subjects were treated with sertraline for 8 weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/IL-10 ratio. These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD. Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment. These findings may help explain the increased risk of comorbid medical illnesses in MDD.
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“DAMPs that are known to activate NLRP3 are increased in patients with mood disorders, with examples including HSPs, reactive oxygen species and other markers of oxidative stress such as xanthine oxidase, peroxides and F2-isoprostanes51–53.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [52]
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“In depression, OS plays a crucial role. 131 , 132”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [132]
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The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942
Major depressive disorder: hypothesis, mechanism, prevention and treatment
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“131,132 The brain is particularly sensitive to OS due to numerous variables, including rapid oxidative energy metabolism (a process through which ROS, which are harmful molecules, are constantly produced), high levels of unsaturated fatty acids (which are vulnerable to lipid peroxidation), and…”
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Is depression associated with increased oxidative stress? A systematic review and meta-analysis
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Metadata
- Authors
- Rawdin, B. J., Mellon, S. H., Dhabhar, F. S., Epel, E. S., Puterman, E., Su, Y., Burke, H. M., Reus, V. I., Rosser, R., Hamilton, S. P., Nelson, J. C., & Wolkowitz, O. M.
- Affiliations
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Corresponding author
- Wolkowitz, O.M.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 31
- Pages
- 143-152
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3669232
- OpenAlex
- W2003062523
- Cited by
- 255
- References
- 126
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 18 · 2023: 12 · 2022: 15 · 2021: 15 · 2020: 21 · 2019: 25 · 2018: 21 · 2017: 20 · 2016: 21 · 2015: 21 · 2014: 25 · 2013: 12
- FWCI
- 5.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R00HL109247)
- National Institute of Mental Health (R01MH083784, R25MH060482)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, chronic inflammation, oxidative stress, F2-isoprostanes, interleukin-6, IL-10, IL-6/IL-10 ratio, sertraline, antidepressant treatment, untreated depression
- MeSH terms
- Adult, Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Inflammation, Male, Middle Aged, Interleukin-6, Interleukin-10, Treatment Outcome, Oxidative Stress, Sertraline
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