Inflammation and post‐traumatic stress disorder

Abstract

While post‐traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted a link between this disorder and alterations in the immune and inflammatory systems. Epidemiological studies have demonstrated that PTSD is associated with significantly increased rates of physical comorbidities in which immune dysregulation is involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, and autoimmune diseases. In line with this, a number of blood biomarker studies have reported that compared to healthy controls, individuals with PTSD exhibit significantly elevated levels of proinflammatory markers, such as interleukin‐1β, interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein. Moreover, various lines of animal and human research have suggested that inflammation is not only associated with PTSD but also can play an important role in its pathogenesis and pathophysiology. In this review, we first summarize evidence suggestive of increased inflammation in PTSD. We then examine findings that suggest possible mechanisms of inflammation in this disorder in terms of two different but interrelated perspectives: putative causes of increased proinflammatory activities and potential consequences that inflammation generates. Given that there is currently a dearth of treatment options for PTSD, possibilities of new therapeutic approaches using pharmacological and non‐pharmacological treatments/interventions that have anti‐inflammatory effects are also discussed. Despite the increasing attention given to the inflammatory pathology of PTSD, there remains much to be elucidated, including more detailed mechanisms of inflammation, potential usefulness of inflammatory biomarkers as diagnostic and prognostic markers, and efficacy of novel treatment strategies targeting inflammation.

Inflammation in Post-Traumatic Stress Disorder (PTSD): A Review of Potential Correlates of PTSD with a Neurological Perspective

“…In the current review, IL-6 demonstrated to be the most documented proinflammatory cytokine in human models of PTSD, and the majority of studies demonstrated increased IL-6 levels in the serum sample of individuals diagnosed with PTSD as compared with their respective control group. This may also be in alignment with previous research which noted IL-6 as the most considerable marker for inflammation [21]. Specifically, studies have shown that IL-6 is crucial in the relationship between immune system and CNS in inflammatory states [44].…”

“…Here, the premise is that individuals who are at risk for PTSD have a distinct proinflammatory state prior to any exposure to trauma as compared with resilient individuals. Another perspective is the distinct responsiveness towards trauma that may vary according to genetic factors [21], such as the ALOX12 locus as described in Table 4 [74]. Since the activation of many genes including ALOX12, ALOX15, and RORA have shown to alter according to oxidative stress in a PTSD model [108], a targeted approach that observes for the relationship between inflammation and trauma exposure according to genetic variants may identify the risk or resilience factors of PTSD.…”

“…A number of reviews have also been published that discuss the inflammatory changes in a human PTSD model. In particular, articles investigated inflammation as observable through specific serum inflammatory markers that are known to be in association with PTSD [21,22] and conducted meta-analysis and meta-regression [23] as to summarize elevated systemic levels of oxidative stress and inflammation in individuals with PTSD as compared to healthy controls. However, reviews on the topic of inflammation and PTSD have demonstrated inconsistent findings, which have been suggested to be the result of the heterogeneity of the disorder.…”

“…A comprehensive and updated review on the growing literature that were recently published on inflammation in PTSD according to various factors that potentially contribute to the heterogeneity may explain for the contrasting findings that were discussed to date. Considering that a few studies in the past have suggested that specific inflammatory markers may play an important role specifically in PTSD [25] and previous articles suggested specific biomarkers as promising for indicating inflammation in PTSD [21], summarizing findings from recent literature on such specified markers may help identify potential biological markers that indicate one's pathophysiology of PTSD.…”

Eicosapentaenoic Acid Intake Associated with Reduced Risk of Posttraumatic Stress Disorder after the Great East Japan Earthquake and Tsunami

“…Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition characterized by intrusion, avoidance, hyperarousal, and other symptoms, which occurs in response to an array of traumatic events including physical, sexual, or mental abuse; wartime experiences; or being the victim of a violent crime [1]. The resulting stress can cause a pro-inflammatory response in the brain characterized primarily by the complex release of inflammatory mediators such as cytokines, prostanoids, free radicals, and transcription factors, as well as subsequent brain inflammatory responses, which further contribute to cell damage [2,3]. Conventional treatment for PTSD includes pharmacotherapy, psychotherapy, and psychophysiological therapy, although it is often resistant to these treatments [4].…”