Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress

Daniel Lindqvist, Owen M. Wolkowitz, Synthia Mellon, Rachel Yehuda, Janine D. Flory, Clare Henn-Haase, Linda M. Bierer, Duna Abu-Amara, Michelle Coy, Thomas C. Neylan, Iouri Makotkine, Victor I. Reus, Xiaodan Yan, Nicole M. Taylor, Charles R. Marmar, Firdaus Dhabhar

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalBrain, Behavior, and Immunity
Volume42
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Post-Traumatic Stress Disorders
Psychological Stress
Depression
Lymphotoxin-beta
Wounds and Injuries
Interleukin-1
C-Reactive Protein
Interferons
Interleukin-6
Cytokines
Inflammation
Hypersensitivity
Body Mass Index
Asthma

Keywords

  • Combat
  • Cytokines
  • Depression
  • Early life trauma
  • Inflammation
  • Post-traumatic stress disorder (PTSD)

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. / Lindqvist, Daniel; Wolkowitz, Owen M.; Mellon, Synthia; Yehuda, Rachel; Flory, Janine D.; Henn-Haase, Clare; Bierer, Linda M.; Abu-Amara, Duna; Coy, Michelle; Neylan, Thomas C.; Makotkine, Iouri; Reus, Victor I.; Yan, Xiaodan; Taylor, Nicole M.; Marmar, Charles R.; Dhabhar, Firdaus.

In: Brain, Behavior, and Immunity, Vol. 42, 01.01.2014, p. 81-88.

Research output: Contribution to journalArticle

Lindqvist, D, Wolkowitz, OM, Mellon, S, Yehuda, R, Flory, JD, Henn-Haase, C, Bierer, LM, Abu-Amara, D, Coy, M, Neylan, TC, Makotkine, I, Reus, VI, Yan, X, Taylor, NM, Marmar, CR & Dhabhar, F 2014, 'Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress', Brain, Behavior, and Immunity, vol. 42, pp. 81-88. https://doi.org/10.1016/j.bbi.2014.06.003
Lindqvist, Daniel ; Wolkowitz, Owen M. ; Mellon, Synthia ; Yehuda, Rachel ; Flory, Janine D. ; Henn-Haase, Clare ; Bierer, Linda M. ; Abu-Amara, Duna ; Coy, Michelle ; Neylan, Thomas C. ; Makotkine, Iouri ; Reus, Victor I. ; Yan, Xiaodan ; Taylor, Nicole M. ; Marmar, Charles R. ; Dhabhar, Firdaus. / Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress. In: Brain, Behavior, and Immunity. 2014 ; Vol. 42. pp. 81-88.
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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.",
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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

PY - 2014/1/1

Y1 - 2014/1/1

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.

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KW - Cytokines

KW - Depression

KW - Early life trauma

KW - Inflammation

KW - Post-traumatic stress disorder (PTSD)

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