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.

中文翻译：

---

创伤后应激障碍和炎症：解开双向性问题

创伤后应激障碍 (PTSD) 越来越多地与全身炎症加剧有关。这种关联是因果关系（双向或单向）还是相关关系很重要。研究人员假设，慢性全身性低度炎症可能会在经历创伤后增加患 PTSD 的风险和/或作为将 PTSD 与不良身体健康结果联系起来的机制。然而，如果 PTSD 与炎症的关系是相关的，则可能不值得进一步研究旨在将炎症理解为 PTSD 风险因素或将 PTSD 与健康状况不佳联系起来的途径。在这篇综述中，我们首先评估与 PTSD 和炎症相关的纵向证据，以更清楚地了解这种关系的方向性和因果性质。全面的，很少有纵向研究严格评估 PTSD 与炎症关系的方向。一些证据表明，评估创伤前或创伤后急性后果的炎症升高会增加患 PTSD 的风险。评估 PTSD 对后续炎症水平的影响的研究较少，结果喜忧参半。样本特征和研究设计，以及炎症相关测量的类型，在不同研究中差异很大。根据目前的证据，我们随后推荐了几种统计和研究设计方法，这些方法可能有助于解决双向性问题，并有助于确定 PTSD 与炎症之间的因果关系方向。最后，我们总结了未来的研究方向，并根据越来越多的文献考虑了干预或治疗方法的潜在影响。