Holistic Rehabilitation: Biological Embedding of Social Adversity and Its Health Implications.

Human health is affected by lived experiences, both past and present. The environments we encounter throughout our lives, therefore, shape how we respond to new challenges, how we maintain a healthy immune system, and even how we respond to treatment and rehabilitation. Early in life and throughout adulthood, social experiences-such as exposure to various forms of adversity-can alter how cells in our body function, with far-reaching consequences for human health, disease, and treatment. This Perspective highlights studies from an ever-growing body of literature on the social determinants of health, with a focus on exposure to social adversities, such as social isolation, discrimination, or low social status, experienced both early in life and adulthood and how they variably impact health. By focusing on recent observational studies in humans and experimental studies on social nonhuman animals, this article details how social adversity can become biologically embedded in our cells at the molecular level. Given that humans are social animals, it is no surprise that social adversity can negatively impact our health, and experimental animal studies have helped us to uncover some of the causal mechanistic pathways underlying the link between social adversity and health outcomes. These molecular consequences can have far-reaching implications and, when combined with our growing knowledge on the social determinants of health, should inform how we approach treatment and rehabilitation.

Social and ecological drivers of reproductive seasonality in geladas.

Many nonseasonally breeding mammals demonstrate some degree of synchrony in births, which is generally associated with ecological factors that mediate fecundity. However, disruptive social events, such as alpha male replacements, also have the potential to affect the timing of female reproduction. Here, we examined reproductive seasonality in a wild population of geladas (Theropithecus gelada) living at high altitudes in an afro-alpine ecosystem in Ethiopia. Using 9 years of demographic data (2006-2014), we determined that, while females gave birth year-round, a seasonal peak in births coincided with peak green grass availability (their staple food source). This post-rainy season "ecological peak" in births meant that estimated conceptions for these births occurred when temperatures were at their highest and mean female fecal glucocorticoid concentrations were at their lowest. In addition to this ecological birth peak, we also found a separate birth peak that occurred only for females in groups that had experienced a recent replacement of the dominant male (i.e., a takeover). Because new dominant males cause abortions in pregnant females and kill the infants of lactating females, takeovers effectively "reset" the reproductive cycles of females in the group. This "social birth peak" was distinct from the ecological peak and was associated with higher rates of cycling and conceptions overall and higher glucocorticoid levels immediately following a takeover as compared to females that did not experience a takeover. These data demonstrate that social factors (in this case, male takeovers) can contribute to population-level reproductive seasonality above and beyond group-level reproductive synchrony.

Social status alters immune regulation and response to infection in macaques.

Social status is one of the strongest predictors of human disease risk and mortality, and it also influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined genomics with a social status manipulation in female rhesus macaques to investigate how status alters immune function. We demonstrate causal but largely plastic social status effects on immune cell proportions, cell type-specific gene expression levels, and the gene expression response to immune challenge. Further, we identify specific transcription factor signaling pathways that explain these differences, including low-status-associated polarization of the Toll-like receptor 4 signaling pathway toward a proinflammatory response. Our findings provide insight into the direct biological effects of social inequality on immune function, thus improving our understanding of social gradients in health.