TY - JOUR
T1 - Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress
AU - Lindqvist, Daniel
AU - Wolkowitz, Owen M.
AU - Mellon, Synthia
AU - Yehuda, Rachel
AU - Flory, Janine D.
AU - Henn-Haase, Clare
AU - Bierer, Linda M.
AU - Abu-Amara, Duna
AU - Coy, Michelle
AU - Neylan, Thomas C.
AU - Makotkine, Iouri
AU - Reus, Victor I.
AU - Yan, Xiaodan
AU - Taylor, Nicole M.
AU - Marmar, Charles R.
AU - Dhabhar, Firdaus S.
N1 - Funding Information:
This study was supported by the following grants: U.S. Department of Defense, W81XWH-11-2-0223 (PI: Charles Marmar); U.S. Department of Defense, W81XWH-10-1-0021 (PI: Owen M. Wolkowitz); The Mental Illness Research, Education and Clinical Center (MIRECC). Daniel Lindqvist received postdoc grants from the Swedish Society of Medicine; the Sjobring Foundation; the OM Persson Foundation and the province of Scania (Sweden) state grants (ALF). The authors declare no conflict of interest.
Publisher Copyright:
© 2014.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - Combat
KW - Cytokines
KW - Depression
KW - Early life trauma
KW - Inflammation
KW - Post-traumatic stress disorder (PTSD)
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U2 - 10.1016/j.bbi.2014.06.003
DO - 10.1016/j.bbi.2014.06.003
M3 - Article
C2 - 24929195
AN - SCOPUS:84908621921
VL - 42
SP - 81
EP - 88
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
ER -