Depression as sickness behavior? A test of the host defense hypothesis in a high pathogen population
Open accessAbstract
Sadness is an emotion universally recognized across cultures, suggesting it plays an important functional role in regulating human behavior. Numerous adaptive explanations of persistent sadness interfering with daily functioning (hereafter "depression") have been proposed, but most do not explain frequent bidirectional associations between depression and greater immune activation. Here we test several predictions of the host defense hypothesis, which posits that depression is part of a broader coordinated evolved response to infection or tissue injury (i.e. "sickness behavior") that promotes energy conservation and reallocation to facilitate immune activation. In a high pathogen population of lean and relatively egalitarian Bolivian forager-horticulturalists, we test whether depression and its symptoms are associated with greater baseline concentration of immune biomarkers reliably associated with depression in Western populations (i.e. tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and C-reactive protein [CRP]). We also test whether greater pro-inflammatory cytokine responses to ex vivo antigen stimulation are associated with depression and its symptoms, which is expected if depression facilitates immune activation. These predictions are largely supported in a sample of older adult Tsimane (mean±SD age=53.2±11.0, range=34-85, n=649) after adjusting for potential confounders. Emotional, cognitive and somatic symptoms of depression are each associated with greater immune activation, both at baseline and in response to ex vivo stimulation. The association between depression and greater immune activation is therefore not unique to Western populations. While our findings are not predicted by other adaptive hypotheses of depression, they are not incompatible with those hypotheses and future research is necessary to isolate and test competing predictions.
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A recent systematic review reports effective psychosocial interventions for depression in women experiencing IPV in low and middle income countries.
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- Authors
- Stieglitz, J., Trumble, B. C., Thompson, M. E., Blackwell, A. D., Kaplan, H., & Gurven, M.
- Affiliations
- University of New Mexico (US)
- University of California, Santa Barbara (US)
- Corresponding author
- Stieglitz, Jonathan
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 49
- Pages
- 130-139
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC4567437
- OpenAlex
- W1639240385
- Cited by
- 62
- References
- 75
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 10 · 2017: 6 · 2016: 8 · 2015: 2
- FWCI
- 2.92
- 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)
- Chapman University Digital Commons (Chapman University) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health/National Institute on Aging (R01AG024119, R56AG024119)
- Agence Nationale de la Recherche
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Evolutionary Psychology and Human Behavior
- Keywords
- depression, sickness behavior, immune activation, inflammatory cytokines, C-reactive protein, TNF-α, IL-1β, interleukin-6, Tsimane, forager-horticulturalists, adaptive function of emotions, older adults
- MeSH terms
- Bolivia, C-Reactive Protein, Depressive Disorder, Female, Humans, Immunologic Factors, Male, Middle Aged, Biomarkers, Cytokines, Host-Pathogen Interactions, Illness Behavior
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