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

JAMA Psychiatry (Impact Factor: 12.01). 02/2014; 71(4). 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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    • "Indeed, the glucocorticoid receptor gene, NR3C1, has been shown to predict treatment outcome of combat veterans with PTSD (Yehuda et al., 2013). Likewise, inflammatory proteins have been shown to be associated with PTSD in Marines returning from a combat deployment (Eraly et al., 2014). It is widely anticipated that ongoing and future biomarker research will yield biomarkers that will be useful in the diagnosis and treatment of combat-related PTSD. "
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    ABSTRACT: This paper reviews the psychological health research conducted in the United States in support of combat veterans from Iraq and Afghanistan, using the Military Psychological Health Research Continuum, which includes foundational science, epidemiology, etiology, prevention and screening, treatment, follow-up care, and services research. The review is limited to those studies involving combat veterans and military families. This review discusses perplexing issues regarding the impact of combat on the mental health of service members such as risk and resilience factors of mental health, biomarkers of posttraumatic stress syndrome (PTSD), mental health training, psychological screening, psychological debriefing, third location decompression, combat and suicide, the usefulness of psychotherapy and drug therapy for treating PTSD, role of advanced technology, telemedicine and virtual reality, methods to reduce stigma and barriers to care, and best approaches to the dissemination of evidence-based interventions. The mental health research of special populations such as women, National Guardsmen and reservists, and military families is also presented. The review concludes by identifying future areas of research.
    European Journal of Psychotraumatology 08/2014; 5. DOI:10.3402/ejpt.v5.24713 · 2.40 Impact Factor
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    • "In line with this notion, a study in children who were involved in motor vehicle accidents found that higher IL-6 levels within 24 h after the accident predicted a diagnosis of PTSD six months later (Pervanidou et al., 2007). Moreover, Eraly et al. recently reported, in a large-scale study on U.S. Marines, that high CRP levels pre-deployment were predictive of more severe PTSD symptomatology (assessed by means of CAPS) three months after deployment (Eraly et al., 2014). Another prospective study of inflammatory markers, however, did not bear out this relationship (Sutherland et al., 2008). "
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    ABSTRACT: Background: Chronic inflammation may be involved in combat-related post-traumatic stress disorder (PTSD) and may help explain comorbid physical diseases. However, the extent to which combat exposure per se, depression, or early life trauma, all of which are associated with combat PTSD, may confound the relationship between PTSD and inflammation is unclear. Methods: We quantified interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and C-reactive protein (CRP) in 51 combat-exposed males with PTSD and 51 combat-exposed males without PTSD, and assessed PTSD and depression severity as well as history of early life trauma. To decrease the possibility of Type I errors, we summed standardized scores of IL-1β, IL-6, TNFα, IFNγ and CRP into a total "pro-inflammatory score". PTSD symptom severity was assessed with the Clinician Administered PTSD Scale (CAPS) rating scale. Results: Subjects with PTSD had significantly higher pro-inflammatory scores compared to combat-exposed subjects without PTSD (p=0.006), and even after controlling for early life trauma, depression diagnosis and severity, body mass index, ethnicity, education, asthma/allergies, time since combat and the use of possibly confounding medications (p=0.002). Within the PTSD group, the pro-inflammatory score was not significantly correlated with depressive symptom severity, CAPS total score, or with the number of early life traumas. Conclusions: Combat-related PTSD in males is associated with higher levels of pro-inflammatory cytokines, even after accounting for depression and early life trauma. These results, from one of the largest studies of inflammatory cytokines in PTSD to date, suggest that immune activation may be a core element of PTSD pathophysiology more so than a signature of combat exposure alone.
    Brain Behavior and Immunity 06/2014; 42. DOI:10.1016/j.bbi.2014.06.003 · 5.89 Impact Factor
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    ABSTRACT: Susceptibility to PTSD is determined by both genes and envi-ronment. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between pe-ripheral blood and brain. Therefore, our objectives were to test the following hypotheses: (1) pre-trauma expression levels of a gene subset (particularly immune-system genes) in peripheral blood would differ between trauma-exposed Marines who later developed PTSD and those who did not; (2) a predictive bio-marker panel of the eventual emergence of PTSD among high-risk individuals could be developed based on gene expression in How to Cite this Article:
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