Inflammation is a stronger predictor of psychological trauma exposure than behavior in repeated social defeat

Abstract

Post-traumatic stress disorder (PTSD) is a psychiatric illness that results in an increased risk for a variety of inflammatory diseases. The exact etiology of this increased risk in unknown, and thus, several animal models have been developed to investigate the neuroimmune interactions of PTSD. Repeated social defeat stress (RSDS) is an established preclinical model of psychological trauma that recapitulates certain behavioral and inflammatory aspects of human PTSD. Furthermore, RSDS has been utilized to subgroup animals into susceptible and resilient populations based on one specific behavioral phenotype (i.e., social interaction). Herein, we conducted an extensive investigation of circulating inflammatory proteins after RSDS, and found significant elevations in various cytokines and chemokines after exposure to psychological trauma. When categorizing animals into either susceptible or resilient populations based on social interaction, we found no inflammatory or other behavioral differences between these subgroups. Furthermore, assessment of associations between all detectable inflammatory proteins and behavioral outputs found no significant correlation between social interaction parameters and inflammation. In contrast, we identified a panel of 5 circulating inflammatory proteins that showed significant associations with elevated zero maze parameters. Strikingly, these 5 circulating inflammatory proteins displayed a stronger predictive ability of psychological trauma exposure compared to any behavioral outcome. These findings provide new insights into inflammatory markers associated with RSDS, and their ability to predict psychological trauma exposure more robustly than commonly utilized behavioral paradigms. HighlightsO_LIRepeated social defeat stress (RSDS) reproducibly produces peripheral inflammation C_LIO_LIPeripheral inflammation is not coupled to social interaction testing parameters C_LIO_LISusceptible and resilient categorization does not reflect peripheral inflammation C_LIO_LIAnxiety-like behavioral parameters are linked to peripheral inflammation in RSDS C_LIO_LIPeripheral inflammation is more predictive of trauma than behavior in RSDS C_LI