Neural predictors of inflammatory responses to social stress
Psychological stress is associated with a variety of negative physical and mental health outcomes. Recent research suggests that inflammation may be a key biological mediator of the relationship between stress and health, though the neurocognitive pathways engaged during stressors that underlie inflammatory response are largely known. Therefore, the present dissertation project examined the neural systems that are related to inflammatory responses to social stress. This is the first known study to examine how the brain processes social stress and how the inflammatory system responds to the same stressor. To accomplish this goal, healthy, female participants (n = 31) were exposed to a social evaluative stressor while they underwent a functional MRI (fMRI) scan. Blood samples taken before and after the scan were assayed for levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Additional blood samples were used to measure gene expression in immune cells. Changes in pro-inflammatory cytokines and pro-inflammatory gene expression from pre- to post-scan were then linked with neural activity during the social evaluation task. Paper 1 reports results linking neural activity during negative social feedback (compared to neutral feedback) and stressor-evoked changes in pro-inflammatory cytokine levels. Data indicated that exposure to the social stressor was associated with significant increases in IL-6, and greater increases in IL-6 were associated with greater neural activity in the amygdala and the dorsomedial prefrontal cortex (DMPFC) during negative social feedback. Functional connectivity analyses revealed that individuals who showed heightened inflammatory responses to the stressor also showed greater coupling of the DMPFC and amygdala during negative feedback, compared to those who showed a lower inflammatory response. Paper 2 explores the neural systems associated with changes in pro-inflammatory gene expression in response to social evaluation. As predicted, exposure to the social stressor was associated with increases in pro-inflammatory gene expression. Results also indicated that greater neural activity in the DMPFC and the dACC in response to the social evaluation was associated with greater upregulation of pro-inflammatory genes following the stressor. Together, these studies provide initial empirical evidence for the neurocognitive mechanisms that may link social stress with inflammation and disease.