Greater amygdala activity and dorsomedial prefrontal-amygdala coupling are associated with enhanced inflammatory responses to stress

Abstract

Psychological stress is implicated in the etiology of many common chronic diseases and mental health disorders. Recent research suggests that inflammation may be a key biological mediator linking stress and health. Nevertheless, the neurocognitive pathways underlying stress-related increases in inflammatory activity are largely unknown. The present study thus examined associations between neural and inflammatory responses to an acute laboratory-based social stressor. Healthy female participants (n=31) were exposed to a brief episode of stress while they underwent an fMRI scan. Blood samples were taken before and after the stressor, and plasma was assayed for markers of inflammatory activity. Exposure to the stressor was associated with significant increases in feelings of social evaluation and rejection, and with increases in levels of inflammation. Analyses linking the neural and inflammatory data revealed that heightened neural activity in the amygdala in response to the stressor was associated with greater increases in inflammation. Functional connectivity analyses indicated that individuals who showed stronger coupling between the amygdala and the dorsomedial prefrontal cortex (DMPFC) also showed a heightened inflammatory response to the stressor. Interestingly, activity in a different set of neural regions was related to increases in feelings of social rejection. These data show that greater amygdala activity in response to a stressor, as well as tighter coupling between the amygdala and the DMPFC, are associated with greater increases in inflammatory activity. Results from this study begin to identify neural mechanisms that might link stress with increased risk for inflammation-related disorders such as cardiovascular disease and depression.

Keywords: Amygdala; IL-6; Inflammation; Medial prefrontal cortex; Neuroimaging; Social rejection; Social stress; Stress; fMRI.

Conflict of interest statement

Conflict of interest

The authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Fig. 1

Social stress task used in the fMRI scanner. Participants viewed a grid of adjective “buttons”, and every 11–12 s, one of the “buttons” was depressed by a mouse cursor that was supposedly controlled by an evaluator (actually a pre-made video). Pictured is an example of a negative word (i.e., annoying) being selected.

Fig. 2

. Relations between neural activity in the left amygdala (from the contrast of negative > neutral social feedback) and inflammatory responses to the social stressor as measured by log-transformed IL-6 increases from baseline to T90 (in pg/mL). The left side depicts the cluster within left amygdala that was positively correlated with IL-6 responses from a whole-brain regression analysis, and the right side shows a scatter plot of parameter estimates from the left amygdala cluster and IL-6 responses.

Fig. 3

Panel A depicts the anatomical ROI of the left amygdala that was used as a seed region in the PPI analysis (left), and the region in DMPFC that was more strongly correlated with left amygdala activity for high IL-6 responders (compared to low IL-6 responders) during negative (vs. neutral) feedback (right). Panel B depicts the anatomical ROI of the right amygdala that was used as a seed region in the PPI analysis (left), and the region in DMPFC that was more strongly correlated with right amygdala activity for high IL-6 responders (compared to low IL-6 responders) during negative (vs. neutral) feedback (right).