Assessment of Plasma C-Reactive Protein as a Biomarker of Posttraumatic Stress Disorder Risk

Abstract

IMPORTANCE Posttraumatic stress disorder (PTSD) has been associated in cross-sectional studies with peripheral inflammation. It is not known whether this observed association is the result of PTSD predisposing to inflammation (as sometimes postulated) or to inflammation predisposing to PTSD.OBJECTIVE To determine whether plasma concentration of the inflammatory marker C-reactive protein (CRP) helps predict PTSD symptoms. DESIGN, SETTING, AND PARTICIPANTSThe Marine Resiliency Study, a prospective study of approximately 2600 war zone-deployed Marines, evaluated PTSD symptoms and various physiological and psychological parameters before deployment and at approximately 3 and 6 months following a 7-month deployment. Participants were recruited from 4 all-male infantry battalions imminently deploying to a war zone. Participation was requested of 2978 individuals; 2610 people (87.6%) consented and 2555 (85.8%) were included in the present analysis. Postdeployment data on combat-related trauma were included for 2208 participants (86.4% of the 2555 included) and on PTSD symptoms at 3 and 6 months after deployment for 1861 (72.8%) and 1617 (63.3%) participants, respectively. MAIN OUTCOMES AND MEASURESSeverity of PTSD symptoms 3 months after deployment assessed by the Clinician-Administered PTSD Scale (CAPS). RESULTSWe determined the effects of baseline plasma CRP concentration on postdeployment CAPS using zero-inflated negative binomial regression (ZINBR), a procedure designed for distributions, such as CAPS in this study, that have an excess of zeroes in addition to being positively skewed. Adjusting for the baseline CAPS score, trauma exposure, and other relevant covariates, we found baseline plasma CRP concentration to be a highly significant overall predictor of postdeployment CAPS scores (P = .002): each 10-fold increment in CRP concentration was associated with an odds ratio of nonzero outcome (presence vs absence of any PTSD symptoms) of 1.51 (95% CI, 1.15-1.97; P = .003) and a fold increase in outcome with a nonzero value (extent of symptoms when present) of 1.06 (95% CI, 0.99-1.14; P = .09). CONCLUSIONS AND RELEVANCEA marker of peripheral inflammation, plasma CRP may be prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

“…Similar findings have been described in rodents (Avitsur et al, 2006;Brenhouse and Thompson, 2015;Hennessy et al, 2010b). Furthermore, early-life immune activation has been linked to greater neuroendocrine activation in the context of subsequent stressors (Shanks et al, 1995(Shanks et al, , 2000, and higher baseline levels of inflammation have been associated with greater stressinduced responses in animal models (Hodes et al, 2014) and humans (Eraly et al, 2014;Michopoulos et al, 2015). On the other hand, there is initial evidence that genes coding for pro-inflammatory cytokines could moderate the effect of childhood trauma on brain function.…”

“…Of note, these associations were not simply explained by comorbid depression (Passos et al, 2015). In addition, genetic (Michopoulos et al, 2015) and longitudinal (Eraly et al, 2014) studies suggest that inflammation is a preexisting vulnerability factor for the development of PTSD in trauma-exposed individuals rather than simply a correlate of subjective distress, disease severity, or maladaptive coping strategies following PTSD onset.…”

e-PTSD: an overview on how new technologies can improve prediction and assessment of Posttraumatic Stress Disorder (PTSD)

“…Several studies (Green et al, 2016; Moon, Lee, Kim, & Hwang, 2013; Norte et al, 2013; Rissling et al, 2016; Wahbeh & Oken, 2013) found a decrease in HRV in patients with PTSD, pointing out that PTSD symptoms may be related to decreased parasympathetic control, especially during sleep (which could constitute a state of vulnerability for decreased parasympathetic cardiac control) (Kobayashi, Lavela, & Mellman, 2014). Other studies demonstrated that low HRV as a sign of over-reactivity to stress were present prior to the development of PTSD (Eraly et al, 2014; Minassian et al, 2015). …”

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Studies have been conducted and are underway using both adrenergic antagonists and synthetic glucocorticoids in the context of acute trauma to prevent development of PTSD (Amos et al, 2014). Nevertheless, although increased inflammatory markers including CRP have been shown to predict the subsequent development of PTSD (Eraly et al, 2014;Michopoulos et al, 2015), no studies have determined whether those individuals with increased inflammatory markers are the ones who might be most likely to respond to adrenergic or glucocorticoid agonists. Moreover, whether the success of these interventions is in part due to inhibition of stress-induced inflammatory responses or even through glucocorticoid-mediated trafficking of neuroprotective T cells to the brain has yet to be established.…”