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Original Investigation |

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

Satish A. Eraly, MD, PhD1,2; Caroline M. Nievergelt, PhD2,3,4; Adam X. Maihofer, MS4; Donald A. Barkauskas, PhD5; Nilima Biswas, PhD1; Agorastos Agorastos, MD6; Daniel T. O’Connor, MD1,2; Dewleen G. Baker, MD2,3,4 ; for the Marine Resiliency Study Team
[+] Author Affiliations
1Department of Medicine, University of California, San Diego (UCSD)
2Veterans Affairs (VA) San Diego Healthcare System, San Diego, California
3VA Center of Excellence for Stress and Mental Health, San Diego, California
4Department of Psychiatry, UCSD, La Jolla
5Department of Preventive Medicine, University of Southern California, Los Angeles
6Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
JAMA Psychiatry. 2014;71(4):423-431. doi:10.1001/jamapsychiatry.2013.4374.
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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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Figure 1.
Effects of Baseline Plasma C-Reactive Protein (CRP) Concentration and Other Predictors on Postdeployment Posttraumatic Stress Disorder (PTSD) Symptoms

A, Adjusted odds ratios (AORs) of a nonzero Clinician-Administered PTSD Scale score at visit 2 (CAPS2) associated with 1-SD increases in the indicated variables. B, Adjusted fold changes in CAPS2 associated with 1-SD increases in the indicated variables. Data in A and B are from the zero-inflated negative binomial regression (ZINBR) model summarized in Table 2. C, The AORs of nonzero CAPS2 by baseline plasma CRP concentration category (reference category, ≤1; to convert to nanomoles per liter, multiply by 9.524), as determined by ZINBR and adjusted for the same covariates as the model in Table 2. CAPS0 indicates Clinician-Administered PTSD Scale at visit 0 (baseline); CES, Combat Exposure Scale; and PBE, Post-battle Experiences. Error bars delineate 95% CIs; the y-axes use a log scale. All P values are 2-tailed.aP < .001.bP < .05.cP < .01.dP < .10.

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Figure 2.
Effects of Baseline Plasma C-Reactive Protein (CRP) Concentration and Other Predictors on Postdeployment Posttraumatic Stress Disorder (PTSD) Diagnosis

A, Adjusted odds ratios (AORs) of posttraumatic stress disorder (PTSD) at visit 2 associated with 1-SD increases in the indicated variables. Data are from the binomial logistic regression model summarized in Table 3. The y-axis uses a log scale. B, Baseline plasma CRP concentration of participants without or with PTSD at visit 2, adjusted for the same covariates as the logistic regression model in Table 3. CAPS0 indicates Clinician-Administered PTSD Scale at visit 0 (baseline); CES, Combat Exposure Scale; PBE, Post-battle Experiences. Error bars delineate 95% CIs. All P values are 2-tailed.aP < .001.bP < .05.cP < .10.

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