Assessment of Plasma C-reactive Protein As a Biomarker of Posttraumatic Stress Disorder Risk

Overview

Journal JAMA Psychiatry

Publisher American Medical Association

Specialty Psychiatry

Date 2014 Mar 1

PMID 24576974

Citations 166

Authors

Satish A Eraly

Caroline M Nievergelt

Adam X Maihofer

Donald A Barkauskas

Nilima Biswas

Agorastos Agorastos

Daniel T OConnor

Dewleen G Baker

Affiliations

Soon will be listed here.

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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References

Pitman R, Gilbertson M, Gurvits T, May F, Lasko N, Metzger L . Clarifying the origin of biological abnormalities in PTSD through the study of identical twins discordant for combat exposure. Ann N Y Acad Sci. 2006; 1071:242-54. PMC: 2770249. DOI: 10.1196/annals.1364.019. View

Aurer A, Stavljenic-Rukavina A, Kalenic S, Haban V . Inflammatory mediators in saliva of patients with rapidly progressive periodontitis during war stress induced incidence increase. Coll Antropol. 1999; 23(1):117-24. View

Copeland W, Shanahan L, Worthman C, Angold A, Costello E . Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biol Psychiatry. 2011; 71(1):15-21. PMC: 3586231. DOI: 10.1016/j.biopsych.2011.09.023. View

Harrison N, Brydon L, Walker C, Gray M, Steptoe A, Critchley H . Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009; 66(5):407-14. PMC: 2885494. DOI: 10.1016/j.biopsych.2009.03.015. View

Violanti J, Fekedulegn D, Hartley T, Andrew M, Charles L, Mnatsakanova A . Police trauma and cardiovascular disease: association between PTSD symptoms and metabolic syndrome. Int J Emerg Ment Health. 2006; 8(4):227-37. View

Gimeno D, Kivimaki M, Brunner E, Elovainio M, De Vogli R, Steptoe A . Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2008; 39(3):413-23. PMC: 2788760. DOI: 10.1017/S0033291708003723. View

Elderkin-Thompson V, Irwin M, Hellemann G, Kumar A . Interleukin-6 and memory functions of encoding and recall in healthy and depressed elderly adults. Am J Geriatr Psychiatry. 2012; 20(9):753-63. PMC: 3690956. DOI: 10.1097/JGP.0b013e31825d08d6. View

Rasmusson A, Schnurr P, Zukowska Z, Scioli E, Forman D . Adaptation to extreme stress: post-traumatic stress disorder, neuropeptide Y and metabolic syndrome. Exp Biol Med (Maywood). 2010; 235(10):1150-62. DOI: 10.1258/ebm.2010.009334. View

Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T . Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry. 2007; 13(7):717-28. DOI: 10.1038/sj.mp.4002055. View

10.

De Berardis D, Campanella D, Gambi F, La Rovere R, Carano A, Conti C . The role of C-reactive protein in mood disorders. Int J Immunopathol Pharmacol. 2006; 19(4):721-5. DOI: 10.1177/039463200601900402. View

11.

Raison C, Borisov A, Majer M, Drake D, Pagnoni G, Woolwine B . Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression. Biol Psychiatry. 2008; 65(4):296-303. PMC: 2655138. DOI: 10.1016/j.biopsych.2008.08.010. View

12.

Glass C, Olefsky J . Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 2012; 15(5):635-45. PMC: 4156155. DOI: 10.1016/j.cmet.2012.04.001. View

13.

Wium-Andersen M, Orsted D, Nielsen S, Nordestgaard B . Elevated C-reactive protein levels, psychological distress, and depression in 73, 131 individuals. JAMA Psychiatry. 2012; 70(2):176-84. DOI: 10.1001/2013.jamapsychiatry.102. View

14.

Pepys M, Hirschfield G, Tennent G, Gallimore J, Kahan M, Bellotti V . Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006; 440(7088):1217-21. DOI: 10.1038/nature04672. View

15.

Janicki Deverts D, Cohen S, DiLillo V, Lewis C, Kiefe C, Whooley M . Depressive symptoms, race, and circulating C-reactive protein: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Psychosom Med. 2010; 72(8):734-41. PMC: 3037796. DOI: 10.1097/PSY.0b013e3181ec4b98. View

16.

Mottillo S, Filion K, Genest J, Joseph L, Pilote L, Poirier P . The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010; 56(14):1113-32. DOI: 10.1016/j.jacc.2010.05.034. View

17.

Musselman D, Lawson D, Gumnick J, Manatunga A, Penna S, Goodkin R . Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med. 2001; 344(13):961-6. DOI: 10.1056/NEJM200103293441303. View

18.

Morris A, Zhao L, Ahmed Y, Stoyanova N, De Staercke C, Hooper W . Association between depression and inflammation--differences by race and sex: the META-Health study. Psychosom Med. 2011; 73(6):462-8. PMC: 3951048. DOI: 10.1097/PSY.0b013e318222379c. View

19.

Frodl T, Carballedo A, Hughes M, Saleh K, Fagan A, Skokauskas N . Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder. Transl Psychiatry. 2012; 2:e88. PMC: 3309536. DOI: 10.1038/tp.2012.14. View

20.

Howren M, Lamkin D, Suls J . Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009; 71(2):171-86. DOI: 10.1097/PSY.0b013e3181907c1b. View