An investigation of vago-regulatory and health-behavior accounts for increased inflammation in posttraumatic stress disorder

Abstract

Objective Posttraumatic stress disorder (PTSD) has been linked to chronic inflammation, a condition that poses a risk for cardiovascular disease. Attenuated vagal activity has been proposed as a potential mediator of PTSD and inflammation, although associated behavioral health risks—namely cigarette smoking and alcohol dependence—might also account for that link. Methods Inflammation was quantified by fasting serum concentrations of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-10, and thymus- and activation-regulated chemokine (TARC)/CCL17 collected from 85 participants with PTSD and 82 without PTSD. Latent variable modeling was used to assess the relationship between PTSD symptom severity and inflammation along with potential mediators vagal activity (respiratory sinus arrhythmia; RSA), smoking status, and lifetime alcohol dependence. Results PTSD symptom severity was associated with increased inflammation (β = .18, p = .02). However, this association was reduced in models that adjusted for RSA, smoking status, and lifetime alcohol dependence. Independent mediation effects were deemed significant via bootstrapping analyses. Together, RSA, smoking status, and lifetime alcohol dependence accounted for 95% of the effect of PTSD symptom severity on inflammation. Conclusion Although RSA accounted for a modest proportion of the association between posttraumatic stress and pro-inflammatory responses, behavioral factors – specifically cigarette smoking and alcohol dependence – proved to be larger mediators. The benefits of PTSD treatment may be enhanced by additional interventions aimed at modifying these health behaviors.

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

“…Given the current findings summarized, a potential pathway underlying inflammation in PTSD may be suggested. A major collective finding from this review was elevated serum IL-6 levels in all but one study [48] among the studies reviewed for alteration in proinflammatory cytokines in association with PTSD across various trauma types. Considering that IL-6 has been known to cross the blood-brain barrier (BBB) as an immune mediator [105], it may then be that psychosocial stress as a result of trauma induces elevated peripheral IL-6 concentrations, which then influences the inflammatory cytokines within the brain via crossing of the BBB.…”

“…However, it is noteworthy that contrasting findings were reported by de Oliveira and colleagues (2018) as well as Guo and colleagues (2012), where both proinflammatory cytokines including IL-6 and anti-inflammatory cytokines including IL-4 and IL-10 were positively correlated and elevated in individuals with PTSD as compared to the respective healthy control group [54,72]. Dennis and colleagues (2018) also found that PTSD symptom severity is associated with higher IL-10 levels, which are then mediated by vagal activity, smoking, and alcohol dependence [48]. However, this may be partially explained by the well-distributed sex ratio in this particular study of 87 males and 80 female, considering that previous studies have noted significant sex differences in the patterns of inflammatory marker levels.…”

“…Through the current literature selection, studies have demonstrated that individuals with PTSD have significantly elevated serum levels of proinflammatory cytokines than the respective control group without PTSD. Specifically, individuals with PTSD demonstrated as having higher levels of serum IL-1β [15,25], IL-6 [15,16,25,[41][42][43][44][45][46][47], TNF-α [15,16,25,[42][43][44][46][47][48], IFN-γ [15,47,49], and CRP [42,50] than individuals who have been exposed to trauma but have never developed PTSD. 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.…”

Trauma and Autonomic Dysregulation: Episodic—Versus Systemic—Negative Affect Underlying Cardiovascular Risk in Posttraumatic Stress Disorder

“…Put differently, does NA-related autonomic arousal mediate the association of PTSD symptom severity with 24-hour HRV and endothelial functioning? Considering our previous findings that behavioral risk factors (i.e., smoking, alcohol dependence, sleep disturbance) mediate the association between PTSD and cardiovascular risk (17–20), a secondary goal was to compare the hypothesized mediating effects of NA-related autonomic arousal with those of the behavioral risk factors. We also investigated the potential mediating role that 24-hour NA—including mean NA observed during EMA monitoring and frequency of acute NA episodes—might play in linking PTSD symptom severity with 24-hour HRV and endothelial functioning.…”

Integrated analysis profiles of long non–coding RNAs reveal potential biomarkers across brain regions in post–traumatic stress disorder

“…Post-traumatic stress disorder (PTSD) is a persistent stress response triggered after exposure to a single or a series of stressful or traumatic event directly or indirectly (Kim, et al, 2018, Ronzoni, et al, 2016). The typical clinical symptoms in PTSD patients mainly consists of re-living or avoidance the traumatic event, negative emotions and hyper vigilance (Dennis, et al, 2016). It is diagnosed when these symptoms last for at least one month and cause functional impairment and/or marked distress (Lisieski, et al, 2018).…”