A meta-analysis of differences in IL-6 and IL-10 between people with and without depression: Exploring the causes of heterogeneity
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Epidemiological evidence for the inflammatory hypothesis of depression is largely cross-sectional; people with depression have elevated levels of circulating pro-inflammatory markers compared to people without depression. The limitation of cross sectional research is the potential for extraneous factors to influence observed effects. The purpose of this meta-analysis of cross-sectional studies of interleukin(IL)-6 and IL-10 in people with and without depression is to provide a targeted analysis of potential moderator factors relating to the diagnosis of depression and to physical and psychiatric comorbidity. Electronic searches of Embase and Medline databases were conducted using subject headings "interleukin-6" or "interleukin-10" and those relating to depression. Studies were included if they measured circulating marker levels in serum or plasma in a group of people with and without depressive symptoms (99 studies for IL-6, 19 studies for IL-10). IL-6 was elevated in depressed compared to non-depressed groups (d = 0.46, 99% CI 0.34 to 0.58, I(2) = 85.9%). This effect was larger in subgroups where depressive disorders were diagnosed compared to those with only depressive symptoms via standardized inventory, and subgroups where participants were recruited from inpatient or outpatient settings compared to the general community. The effect was also larger in those who were not selected for a particular comorbidity compared to those selected for cardiovascular disease. IL-10 effect size was not significant (d = -0.31, 99% CI -0.95 to 0.32, I(2) = 94.1%) which was not accounted for in subgroup analyses or meta-regression, indicating there is not a global elevation in cytokines. These data highlight that comorbidity and behavioral aspects of depression need to be measured and controlled in future prospective and experimental research testing the inflammatory hypothesis of depression.
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Compared to nondepressed individuals, depressed individuals who are otherwise healthy exhibit higher circulating levels of IL-1, IL-6, and TNFα, as well as higher levels of CRP.
“compared to nondepressed individuals, depressed individuals (who are otherwise healthy) exhibit higher circulating levels of several proinflammatory cytokines including IL-1, IL-6, and TNFα , as well as higher levels of the systemic inflammatory biomarker CRP”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Hiles, Baker, de Malmanche, & Attia, 2012
The Interleukin-6 results (page unavailable in our copy) report higher circulating IL-6 in depressed than nondepressed groups. The paper does not establish the claimed elevations of IL-1, TNFα, or CRP, and its analysis included some participants selected for medical or psychiatric comorbidities, so it does not establish the full claim for otherwise healthy people. (LLM, conf=0.88)
Experimental — accuracy not yet measuredConcentrations of the anti-inflammatory cytokine IL-10 are lower for depressed than for nondepressed individuals.
“at least one study found that concentrations of the anti-inflammatory cytokine IL-10 are lower for depressed than for nondepressed individuals”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Hiles et al., 2012
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- Authors
- Hiles, S. A., Baker, A. L., de Malmanche, T., & Attia, J.
- Affiliations
- University of Newcastle Australia (AU)
- John Hunter Hospital (AU)
- Corresponding author
- Hiles, Sarah A.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 26
- Issue
- 7
- Pages
- 1180-1188
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1972846275
- Cited by
- 274
- References
- 56
- Citations by year
- 2026: 6 · 2025: 19 · 2024: 11 · 2023: 21 · 2022: 31 · 2021: 15 · 2020: 18 · 2019: 28 · 2018: 21 · 2017: 24 · 2016: 22 · 2015: 20 · 2014: 19 · 2013: 16 · 2012: 3
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion, cc-by-nc-nd)
- Figshare (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- depression, interleukin-6, IL-10, cytokines, depressive symptoms, comorbidities, cardiovascular disease
- MeSH terms
- Cross-Sectional Studies, Data Interpretation, Statistical, Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Inflammation, Inpatients, Life Style, Outpatients, Interleukin-6, Comorbidity, Interleukin-10
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