Dysregulated relationship of inflammation and oxidative stress in major depression

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.

doi:10.1016/j.bbi.2012.11.011

Cited by 255Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

Dysregulated relationship of inflammation and oxidative stress in major depression

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Rawdin, B.J., Mellon, S.H., Dhabhar, F.S., Epel, E.S., Puterman, E., Su, Y., Burke, H.M., Reus, V.I. +4 more·2013·Brain, Behavior, and Immunity

DOI 10.1016/j.bbi.2012.11.011PMC PMC3669232

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Abstract

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 known to activate NLRP3 are increased in patients with mood disorders, including HSPs, reactive oxygen species and other markers of oxidative stress such as xanthine oxidase, peroxides and F2-isoprostanes.
“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]
The Discussion states that reactive oxygen species (ROS) activate NLRP3, and the Introduction reports elevated F2-isoprostanes and other oxidative-stress markers in people with major depressive disorder. But the paper does not establish that HSPs, xanthine oxidase, or peroxides are increased or activate NLRP3 in patients with mood disorders. Its Results (§3.2) also found no significant difference in F2-isoprostane concentrations between its depressed and control groups. (LLM, conf=0.88)
Experimental — accuracy not yet measured
In depression, oxidative stress plays a crucial role.
“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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Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis
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169. Inflammatory and oxidative stress are highly correlated in unmedicated major depression
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Metabolic and Anti-Inflammatory Effects of Antidepressants in Patients Diagnosed with Major Depressive Disorder: A Prospective Cohort StudyPreprint
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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.
ORCID: Mellon, S.H.
Dhabhar, F.S.
Epel, E.S.
Puterman, E.
Reus, V.I.
Hamilton, S.P.
Wolkowitz, O.M.
Venue: Brain, Behavior, and Immunity
Publisher: Elsevier BV
Published: 2013-07
Volume: 31
Pages: 143-152
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2012.11.011
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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 › 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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Dysregulated relationship of inflammation and oxidative stress in major depression

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