Depression as sickness behavior? A test of the host defense hypothesis in a high pathogen population

Jonathan Stieglitz, Benjamin C. Trumble, Melissa Emery Thompson, Aaron D. Blackwell, Hillard Kaplan, Michael Gurven

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)130-139
Number of pages10
JournalBrain, Behavior, and Immunity
StatePublished - Oct 1 2015
Externally publishedYes


  • Depression
  • Evolution
  • Host defense
  • Immune activation
  • Sickness behavior
  • Tsimane

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


Dive into the research topics of 'Depression as sickness behavior? A test of the host defense hypothesis in a high pathogen population'. Together they form a unique fingerprint.

Cite this