The Relationship of Depression and Stressors to Immunological Assays: A Meta-Analytic Review
Abstract
This is a broad meta-analysis of the relations of both depression and stressors to immunological assays. The number of study samples (greater than 180) and measures (greater than 40) is much more extensive than any so far. Analyses are done by both fixed and random effects. By a fixed-effects analysis, both major depression and naturally occurring acute stressors are associated with (1) an overall leukocytosis, (2) mild reductions in absolute NK-cell counts and relative T-cell proportions, (3) marginal increases in CD4/CD8 ratios, and (4) moderate decreases in T- and NK-cell function. However, the degree of heterogeneity of the studies' results raises questions about their robustness. Therefore, we also did the first random effects analysis to estimate what is likely to appear in future studies. For depression, the analysis showed the immunological correlates included (1) an overall leukocytosis, manifesting as a relative neutrophilia and lymphoenia; (2) increased CD4/CD8 ratios; (3) increased circulating haptoglobin, PGE(2), and IL-6 levels; (4) reduced NK-cell cytotoxicity; and (5) reduced lymphocyte proliferative response to mitogen. For stressors, the random effects analysis showed that future studies are likely to find the following effects: (1) an overall leukocytosis, manifesting as an absolute lymphocytosis; (2) alterations in cytotoxic lymphocyte levels, CD4/CD8 ratios, and natural killer cell cytotoxicity with the direction of change depending on the chronicity of t…
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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 Zorrilla et al., 2001
Alterations in T cell characteristics have been reported in patients with major depression.
“alterations in T cell characteristics have been reported in patients with major depression (15–18)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [17]
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- Authors
- Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A., McCorkle, R., Seligman, D. A., & Schmidt, K.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2001-09
- Volume
- 15
- Issue
- 3
- Pages
- 199-226
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W1968248096
- Cited by
- 995
- References
- 12
- Citations by year
- 2026: 9 · 2025: 26 · 2024: 32 · 2023: 29 · 2022: 39 · 2021: 41 · 2020: 99 · 2019: 41 · 2018: 36 · 2017: 43 · 2016: 42 · 2015: 63 · 2014: 50 · 2013: 40 · 2012: 68
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k05da000168-30)
- National Institute of Mental Health (MH 45178)
- National Institute on Drug Abuse (2K05 DA 00168-23A)
- NIH Clinical Center
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- depression, stress, leukocytosis, natural killer cells, T cells, CD4/CD8 ratio, NK cell cytotoxicity, lymphocyte proliferation, cytokines, haptoglobin, immune function, disease susceptibility
- MeSH terms
- Depression, Female, Humans, Leukocyte Count, Male, Monocytes, Neutrophils, Stress, Physiological, Biomarkers, Lymphocyte Subsets, Lymphocyte Count
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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