Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression
Abstract
The first findings that depression is characterized by cell-mediated immune activation and inflammation were published between 1990-1993 (Maes et al.). Recently, it was reported that--based on meta-analysis results--depression is an inflammatory disorder because the plasma levels of two cytokines are increased, i.e. interleukin-(IL)-6 and tumor necrosis factor-α (TNFα). The same meta-analysis found that plasma IL-2 and interferon-(IFN)γ levels are not altered in depression, suggesting that there is no T cell activation in that illness. The present paper reviews the body of evidence that depression is accompanied by cell-mediated immune activation. The findings include: increased serum levels of the soluble IL-2 receptor (sIL-2R) and the sCD8 molecule; increased numbers and percentages of T cells bearing T cell activation markers, such as CD2+CD25+, CD3+CD25+, and HLA-DR+; increased stimulated production of IFNγ; higher neopterin and sTNFR-1 or sTNFR-2 levels; induction of indoleamine 2,3-dioxygenase (IDO) with lowered levels of plasma tryptophan and increased levels of tryptophan catabolites along the IDO pathway (TRYCATs); and glucocorticoid resistance in immune cells. Interferon-α (IFNα)-based immunotherapy shows that baseline and IFNα-induced activation of T cells, IDO activity and TRYCAT formation are related to the development of IFNα-induced depressive symptoms. Animal models of depression show that a cell-mediated immune response is related to the development of depression-like behavior. Antidepressants and mood stabilizers suppress different aspects of cell-mediated immunity and rather specifically target IFNγ production. This review shows that inflammation and cell-mediated immune activation are key factors in depression.
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Depression is accompanied by cell-mediated immune activation, which involves macrophages, monocytes, and T-lymphocytes.
“depression is accompanied not just by increases in circulating markers of inflammation but also by cell-mediated immune activation, which involves macrophages, monocytes, and T-lymphocytes”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Maes, 2011
Cell-mediated immune activation causes tryptophan-related reductions in serotonin, which in turn lead to somatic and neurovegetative symptoms of depression.
“cell-mediated immune activation causes tryptophan-related reductions in serotonin, which in turn lead to somatic and neurovegetative symptoms of depression”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Maes, 2011
Patients with inflammation-associated depression, whether from a comorbid physical illness or from treatment with pro-inflammatory proteins, are at high risk for suicidal ideation.
“the evidence indicates that patients with inflammation-associated depression, whether due to a comorbid physical illness or treatment with pro-inflammatory proteins, are at high risk for suicidal ideation.”
From SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: Research Article: Suicidal Ideation and Inflammation (2013) · cites this paper as [35]
One plausible explanation for the findings is that suicidal ideation is more common in individuals with inflammation-associated depression.
“one plausible explanation for our findings is that suicidal ideation is more common in individuals with inflammation-associated depression.”
From SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: Research Article: Suicidal Ideation and Inflammation (2013) · cites this paper as [35]
Inflammation plays a causal role in the development of at least some forms of depression.
“Inflammation is increasingly recognized as playing a causal role in the development of at least some forms of depression, [3,35]”
From SUICIDAL IDEATION IS ASSOCIATED WITH ELEVATED INFLAMMATION IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: Research Article: Suicidal Ideation and Inflammation (2013) · cites this paper as [35]
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“As reviewed elsewhere, elevated proinflammatory cytokine levels are not the only indication that inflammation may be a key biological mediator of depression (Irwin & Miller, 2007; Maes, 2011; Zorrilla et al., 2001).”
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- Authors
- Maes, M.
- Affiliations
- Piyavate Hospital (TH)
- Corresponding author
- Maes, Michael
- ORCID
- Maes, Michael
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 35
- Issue
- 3
- Pages
- 664-675
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W1997361683
- Cited by
- 544
- References
- 172
- Citations by year
- 2026: 7 · 2025: 35 · 2024: 19 · 2023: 28 · 2022: 41 · 2021: 21 · 2020: 21 · 2019: 34 · 2018: 41 · 2017: 39 · 2016: 44 · 2015: 56 · 2014: 47 · 2013: 37 · 2012: 46
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- 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, neuroinflammation, cell-mediated immunity, cytokines, interleukin-6, TNF-α, interferon-gamma, soluble interleukin-2 receptor, soluble CD8, T cell activation, neopterin, soluble TNF receptors, indoleamine 2,3-dioxygenase, tryptophan catabolites, glucocorticoid resistance, antidepressants, mood stabilizers, animal models of depression
- MeSH terms
- Antidepressive Agents, Mental Disorders, Depression, Female, Humans, Immunity, Cellular, Immunosuppressive Agents, Inflammation, Male, Meta-Analysis as Topic
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