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

Abstract

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 foragerhorticulturalists, 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.

High resting metabolic rate among Amazonian forager‐horticulturalists experiencing high pathogen burden

“…Sickness behavior is common with a pro-inflammatory state, and is associated with more sedentary behavior (Dantzer et al 2008). Depressed affect has been associated with higher inflammatory cytokines and reduced physical activity in Tsimane (Stieglitz et al 2015b). Consistent with these and other associations of prolonged immune investment, osteopenia (Stieglitz et al 2015a), low HDL, LDL and total cholesterol (Gurven et al 2009) and anemia are prevalent conditions among Tsimane.…”

Pathogen–Host Defense in the Evolution of Depression: Insights into Epidemiology, Genetics, Bioregional Differences and Female Preponderance

“…However, these findings must be balanced against more recent work conducted in the lowland jungle of Bolivia among the Tsimane Amerindians, a small-scale society composed of lean forager-horticulturalists with a short average lifespan who live in a high-pathogen environment and thus have significant microbial priming in infancy (Stieglitz et al, 2015b). In all these ways the Tsimane represent a reasonable approximation of environmental and social conditions prototypically confronted by humans in the EEA.…”

Immune function in Amazonian horticulturalists

“…Organisms are expected to regulate immune function carefully because responding to disease is costly: immune responses use energy that could be used for other fitness relevant demands; many responses have the potential to cause collateral damage to the organism itself (Ashley et al, 2012); and illness can involve opportunity costs due to sickness behavior (e.g. reduced productivity) (Stieglitz et al, 2015b). Across species, mounting an immune response decreases growth and reproduction, as resources used for immunity are not available for these competing demands (Sheldon and Verhulst, 1996; Klein and Nelson, 1999; Uller et al, 2006; Blackwell et al, 2010; Abrams and Miller, 2011).…”

“…Yet, several lines of evidence suggest that organisms might vary their relative investment in and reliance on innate versus adaptive immunity depending on their life histories, ontogenetic influences, and environmental circumstances (McDade et al, 2016). For example, compared to specific responses, non-specific inflammatory responses are more likely to cause collateral damage through oxidative stress, and are associated with long-term risks of several chronic diseases, including atherosclerosis, cardiovascular disease, obesity, and depression (Ridker et al, 1998; Pearson et al, 2003; Stieglitz et al, 2015b). An inflammatory response is often the body’s first line of defense against infections and wounds, and the strength of the response is expected to vary based on ecological and phenotypic conditions.…”