Posttraumatic Stress Disorder and Inflammation: Untangling Issues of Bidirectionality.

Posttraumatic stress disorder (PTSD) has increasingly been linked to heightened systemic inflammation. It matters whether this association is causal (and either bidirectional or unidirectional) or correlational. Investigators have hypothesized that chronic systemic low-grade inflammation may contribute to greater risk of developing PTSD after experiencing trauma and/or serve as a mechanism linking PTSD to adverse physical health outcomes. However, if the PTSD-inflammation relation is correlational, it may not warrant further research aimed at understanding inflammation as a PTSD risk factor or as a pathway linking PTSD with poor health. In this review, we first assess the longitudinal evidence related to PTSD and inflammation to understand more clearly the directionality and causal nature of this relation. Overall, few longitudinal studies rigorously assess the direction of the PTSD-inflammation relation. Some of the evidence indicates that elevated inflammation assessed pretrauma or in the acute aftermath of trauma increases risk for developing PTSD. Fewer studies evaluate the influence of PTSD on subsequent inflammation levels, and findings are mixed. Sample characteristics and study designs, and also the type of inflammation-related measure, vary widely across studies. Based on current evidence, we then recommend several statistical and study design approaches that may help untangle issues of bidirectionality and aid in determining the direction of causality between PTSD and inflammation. Last, we conclude with future research directions and consider potential implications for interventions or treatment approaches based on this growing body of literature.