Posttraumatic Stress Disorder and Inflammation: Untangling Issues of Bidirectionality

Sumner, Jennifer A.; Nishimi, Kristen M.; Koenen, Karestan C.; Roberts, Andrea L.; Kubzansky, Laura D.

doi:10.1016/j.biopsych.2019.11.005

Cited by 131Posttraumatic Stress Disorder ResearchStress Responses and CortisolChild Abuse and Trauma

Posttraumatic Stress Disorder and Inflammation: Untangling Issues of Bidirectionality

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Sumner, Jennifer A., Nishimi, Kristen M., Koenen, Karestan C., Roberts, Andrea L., Kubzansky, Laura D.·2020·Biological Psychiatry

DOI 10.1016/j.biopsych.2019.11.005PMC PMC7211139

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Abstract

Posttraumatic stress disorder (PTSD) has increasingly been linked to heightened systemic inflammation. It matters whether this association is causal (and either bidirectional or unidirectional) or correlational. Investigators have hypothesized that chronic systemic low-grade inflammation may contribute to greater risk of developing PTSD after experiencing trauma and/or serve as a mechanism linking PTSD to adverse physical health outcomes. However, if the PTSD-inflammation relation is correlational, it may not warrant further research aimed at understanding inflammation as a PTSD risk factor or as a pathway linking PTSD with poor health. In this review, we first assess the longitudinal evidence related to PTSD and inflammation to understand more clearly the directionality and causal nature of this relation. Overall, few longitudinal studies rigorously assess the direction of the PTSD-inflammation relation. Some of the evidence indicates that elevated inflammation assessed pretrauma or in the acute aftermath of trauma increases risk for developing PTSD. Fewer studies evaluate the influence of PTSD on subsequent inflammation levels, and findings are mixed. Sample characteristics and study designs, and also the type of inflammation-related measure, vary widely across studies. Based on current evidence, we then recommend several statistical and study design approaches that may help untangle issues of bidirectionality and aid in determining the direction of causality between PTSD and inflammation. Last, we conclude with future research directions and consider potential implications for interventions or treatment approaches based on this growing body of literature.

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Recent longitudinal studies provide strong evidence that factors such as depression and PTSD precede and predict higher levels of inflammation in both healthy and patient populations.
“Although numerous studies note that associations between negative psychological health and factors that increase cardiovascular risk are likely bidirectional, recent longitudinal studies provide strong evidence that factors such as depression and PTSD precede and predict higher levels of inflammation in both healthy and patient populations. 118,119,124”
From Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association (2021) · cites this paper as [118]
The PTSD-to-Inflammation section reports longitudinal studies in which PTSD preceded increases in some inflammatory markers. But the Summary describes the findings as mixed and says they preclude strong conclusions about directionality; it does not establish the claimed pattern across both healthy and patient populations. The paper discusses depression only briefly in this context, rather than providing broad support for that part of the claim. Page numbers were not available in our copy. (LLM, conf=0.87)
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Chronic distress is associated with detrimental processes, including hypercoagulability, dyslipidemia, impaired glucose control, and increased inflammatory processes and impaired immune responses.
“Specifically, chronic distress is associated with detrimental processes, including hypercoagulability, dyslipidemia, 112-114 impaired glucose control, 115,116 and increased inflammatory processes and impaired immune responses. 95,117,118”
From Psychological Health, Well-Being, and the Mind-Heart-Body Connection: A Scientific Statement From the American Heart Association (2021) · cites this paper as [118]
The paper’s opening discussion (page not provided) reports elevated inflammatory markers in people with PTSD, and its discussion of mechanisms says PTSD may increase inflammation. It does not establish impaired immune responses, and its focus on PTSD does not support extending the finding to chronic distress generally. The other listed processes have separate citations in the citing sentence. (LLM, conf=0.85)
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[3]Koenen KC, Sumner JA, Gilsanz P, Glymour MM, Ratanatharathorn A, Rimm EB, (2017): PTSD and cardiometabolic disease: improving causal inference to inform practice. Psychol Med 47: 209– 225. 27697083 PMC5214599
[49]Himmerich H, Willmund GD, Zimmermann P, Wolf J-E, Bühler AH, Kirkby KC, (2016): Serum concentrations of TNF-a and its soluble receptors during psychotherapy in German soldiers suffering from combat-related PTSD. Psychiatr Danub 28: 293– 298. 27658839

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Authors: Sumner, J. A., Nishimi, K. M., Koenen, K. C., Roberts, A. L., & Kubzansky, L. D.
Affiliations: University of California, Los Angeles (US)
Harvard University (US)
Corresponding author: Sumner, Jennifer A.
ORCID: Sumner, Jennifer A.
Nishimi, Kristen M.
Koenen, Karestan C.
Roberts, Andrea L.
Kubzansky, Laura D.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2020-05
Volume: 87
Issue: 10
Pages: 885-897
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2019.11.005
PMC: PMC7211139
OpenAlex: W2985450080
Cited by: 131
References: 76
Citations by year: 2026: 13 · 2025: 20 · 2024: 20 · 2023: 32 · 2022: 25 · 2021: 15 · 2020: 5
FWCI: 1.78
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health
Topics: Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Keywords: post-traumatic stress disorder, systemic inflammation, bidirectionality, causal direction, low-grade inflammation, trauma exposure, PTSD risk factors, physical health outcomes, longitudinal evidence, study design recommendations, inflammatory markers
MeSH terms: Humans, Inflammation, Longitudinal Studies, Risk Factors, Stress Disorders, Post-Traumatic

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Posttraumatic Stress Disorder and Inflammation: Untangling Issues of Bidirectionality

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