Proinflammatory milieu in combat-related PTSD is independent of depression and early life stress
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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Combining concentrations of IL-1β, IL-6, TNF-α, IFN-γ, and CRP into a single pro-inflammatory score indicates that inflammation is elevated in PTSD.
“Combining concentrations of IL-1β, IL-6, TNF-α, IFN-γ, and CRP into a single pro-inflammatory score also indicated that inflammation is elevated in PTSD (Lindqvist et al, 2014b).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Lindqvist et al, 2014b
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- Authors
- Lindqvist, D., Wolkowitz, O. M., Mellon, S., Yehuda, R., Flory, J. D., Henn-Haase, C., Bierer, L. M., Abu-Amara, D., Coy, M., Neylan, T. C., Makotkine, I., Reus, V. I., Yan, X., Taylor, N. M., Marmar, C. R., & Dhabhar, F. S.
- Affiliations
- University of California, San Francisco (US)
- James J. Peters VA Medical Center (US)
- NYU Langone Health (US)
- Stanford Medicine (US)
- Corresponding author
- Wolkowitz, Owen M.
- Marmar, Charles R.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 42
- Pages
- 81-88
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W2043275406
- Cited by
- 213
- References
- 25
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 10 · 2023: 13 · 2022: 21 · 2021: 20 · 2020: 21 · 2019: 15 · 2018: 26 · 2017: 30 · 2016: 18 · 2015: 10 · 2014: 6
- FWCI
- 25.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Ohio State University
- Svenska Läkaresällskapet
- School of Medicine, New York University
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- combat-related posttraumatic stress disorder, chronic inflammation, inflammatory cytokines, interleukin-6, IL-1β, TNF-α, interferon-gamma, C-reactive protein, depression, early trauma, combat exposure, immune activation, PTSD pathophysiology
- MeSH terms
- Adult, C-Reactive Protein, Combat Disorders, Depressive Disorder, Humans, Inflammation, Life Change Events, Male, Military Personnel, Stress Disorders, Post-Traumatic, Stress, Psychological, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Interleukin-1beta, Young Adult
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