Doctoral Dissertation Research: Evaluating the impact of variable social belonging levels in inflammatory markers

Humans live in social groups, but current biocultural changes have led to significant variation in levels of social connectedness or belonging, which may activate the neuro-immune networks that regulate inflammation. Inflammation is a form of stress response that can have negative health effects, but that is also necessary for adaptation and health. To date, studies of social connectedness and inflammation are limited to individuals from populations with similar levels of social belonging, and these studies emphasize negative social conditions, so that the impact of positive social connections remain understudied. This Doctoral Dissertation Research project adopts a biocultural approach to investigate how variations in belonging affect inflammatory regulation dynamics among adults from social contexts with varying levels of belonging. The study integrates iterative ethnography, with surveys and minimally invasive biological sampling to identify the conditions under which varying levels of connectedness may lead to adaptive or maladaptive inflammatory levels. The study builds STEM capacity through student training, and expands its impact through outreach activities. Scientists have demonstrated that the inflammatory system is sensitive to social experiences such as belonging and exclusion. Social threats can activate the same conserved neuro-inflammatory pathways as physical ones, involving the hypothalamic pituitary adrenocortical (HPA) axis and the sympathetic nervous system’s regulation of acute inflammation. Chronic activation of these pathways can lead to a conserved transcriptional response to adversity (CTRA) and promote a pro-inflammatory phenotype by impairing the downregulation of inflammation in innate immune cells. While ex-vivo cell culture models have advanced our understanding of these processes, they remain limited by costly and invasive sampling methods that require sterile laboratory conditions. Moreover, the effects of positive social connections on inflammation regulation remain underexplored. This Doctoral Dissertation Research project contributes to biocultural frameworks of belonging and inflammatory regulation by: 1) developing a culturally and geographically specific measure of belonging among peoples experiencing different cultural conditions, 2) adapting an ex-vivo cell culture protocol with dried blood spots for use in field settings, and 3) synthesizing novel data to elucidate how diverse social contexts influence biological variation and health in increasingly complex social settings. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.