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

Article (PDF Available)inJAMA Psychiatry 71(4) · February 2014with88 Reads
DOI: 10.1001/jamapsychiatry.2013.4374
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 PARTICIPANTS The 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 MEASURES Severity of PTSD symptoms 3 months after deployment assessed by the Clinician-Administered PTSD Scale (CAPS). RESULTS We 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 RELEVANCE A marker of peripheral inflammation, plasma CRP may be prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.

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Available from: Agorastos Agorastos, Aug 21, 2014
    • "In a report from the MRS, peripheral inflammation was reported to be predictive of PTSD development. Pre-deployment higher plasma concentrations of C-reactive protein (CRP), a marker of peripheral inflammation , were predictive of PTSD emergence (Eraly et al., 2014). No GC-related measures have as yet been reported from the MRS study. "
    [Show abstract] [Hide abstract] ABSTRACT: Although biological systems have evolved to promote stress-resilience, there is variation in stress-responses. Understanding the biological basis of such individual differences has implications for understanding Posttraumatic Stress Disorder (PTSD) etiology, which is a maladaptive response to trauma occurring only in a subset of vulnerable individuals. PTSD involves failure to reinstate physiological homeostasis after traumatic events and is due to either intrinsic or trauma-related alterations in physiological systems across the body. Master homeostatic regulators that circulate and operate throughout the organism, such as stress hormones (e.g., glucocorticoids) and immune mediators (e.g., cytokines), are at the crossroads of peripheral and central susceptibility pathways and represent promising functional biomarkers of stress-response and target for novel therapeutics.
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    • "Clinical studies of immune mediators in PTSD have focused on peripheral immune markers, such as IL-6 and C-reactive protein (CRP). Several studies have established a relationship between elevated CRP and PTSD (Eraly et al., 2014; Groer et al., 2015; Heath et al., 2013; Spitzer et al., 2010), and polymorphisms within the CRP gene have been linked to higher PTSD symptom and CRP levels (Michopoulos et al., 2015). Abnormal inflammatory profiles in Gulf War veterans have been linked to higher PTSD symptom severity and reduced hippocampal volume, suggesting that inflammation might after brain function (O'Donovan et al., 2015 ). "
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    • "Spitzer et al. (2010) found an almost twofold higher odds for elevated C-reactive protein (CRP) levels in subjects with PTSD, again suggesting that low-grade inflammation might be a pathway from PTSD to poor physical health. Similarly, Eraly et al. (2014) suggest that CRP, a marker of peripheral inflammation, may be prospectively associated with PTSD symptom emergence, and that individuals with lesser inflammatory activity may be relatively resilient while those with greater inflammatory activity may be more vulnerable to developing PTSD symptoms. Both CRP and SP are also associated with immune function (Tegeler et al., 2016; Garcia-Recio and Gascón, 2015). "
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