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Assessment of Plasma C-Reactive Protein as a Biomarker of Posttraumatic Stress Disorder Risk
Open accessAbstract
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, higher pre-deployment concentrations of CRP increase postdeployment risk for development of PTSD (Eraly et al, 2014).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Eraly et al, 2014
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“Although no data as yet prospectively demonstrate that chronic PTSD results in augmented inflammation, prospective studies have begun to show that higher levels of inflammation prior to trauma exposure increases risk for subsequent development of PTSD following trauma exposure (Breen et al, 2015;Eraly et al, 2014;Glatt et al, 2013;Tylee et al, 2015).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Eraly et al, 2014
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Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment
Khandaker, G. M., Cousins, L., Deakin, J., Lennox, B. R., Yolken, R., & Jones, P. B. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(14)00122-9 · Cited by 926
Post-traumatic stress disorder.
Yehuda, R., Hoge, C. W., McFarlane, A. C., Vermetten, E., Lanius, R. A., Nievergelt, C. M., Hobfoll, S. E., Koenen, K. C., Neylan, T. C., & Hyman, S. E. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.57 · Cited by 870
Self-citationInflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond
Michopoulos, V., Powers, A., Gillespie, C. F., Ressler, K. J., & Jovanovic, T. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.146 · Cited by 786
Post-Traumatic Stress Disorder
Shalev, A. Y., Liberzon, I., & Marmar, C. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1612499 · Cited by 852
The resilience framework as a strategy to combat stress-related disorders
Kalisch, R., Baker, D. G., Basten, U., Boks, M. P., Bonanno, G. A., Brummelman, E., Chmitorz, A., Fernàndez, G., Fiebach, C. J., Galatzer-Levy, I., et al. (2017) · Nature Human Behaviour · doi:10.1038/s41562-017-0200-8 · Cited by 782
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Metadata
- Authors
- Eraly, S. A., Nievergelt, C. M., Maihofer, A. X., Barkauskas, D. A., Biswas, N., Agorastos, A., O’Connor, D. T., & Baker, D. G.
- Affiliations
- University of California San Diego (US)
- University of Southern California (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Baker, Dewleen G.
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2014-04-01
- Volume
- 71
- Issue
- 4
- Pages
- 423
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC4032578
- OpenAlex
- W2100635378
- Cited by
- 386
- References
- 81
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 33 · 2023: 47 · 2022: 36 · 2021: 28 · 2020: 27 · 2019: 22 · 2018: 29 · 2017: 37 · 2016: 39 · 2015: 30 · 2014: 10
- FWCI
- 45.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL094728, HL094728)
- National Institute of Mental Health (MH093500, R01MH093500)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- post-traumatic stress disorder, C-reactive protein, biomarkers, peripheral inflammation, combat deployment, military personnel, PTSD risk prediction, zero-inflated negative binomial regression, Clinician-Administered PTSD Scale, PTSD symptom severity, PTSD prevention
- MeSH terms
- Adult, C-Reactive Protein, Combat Disorders, Humans, Inflammation, Longitudinal Studies, Male, Military Personnel, Neuropsychological Tests, Predictive Value of Tests, Prospective Studies, Stress Disorders, Post-Traumatic, Biomarkers, Risk Assessment, Resilience, Psychological
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