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Cited by 86Posttraumatic Stress Disorder ResearchStress Responses and CortisolNeuroinflammation and Neurodegeneration Mechanisms

Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans

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O’Donovan, Aoife, Chao, Linda L., Paulson, Jennifer, Samuelson, Kristin W., Shigenaga, Judy K., Grunfeld, Carl, Weiner, Mike W., Neylan, Thomas C.·2015·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2014.11.010PMC PMC4374733
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Abstract

Background Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD. Methods We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5Tesla magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII. Results Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (β=-0.14, p=0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (β=0.24, p=0.04) and reduced IL-6 levels (β=-0.24, p=0.04). Conclusions Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms.

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  • Reduced hippocampal volume is associated with increased inflammation and more severe PTSD symptoms in veterans.

    “In turn, reduced hippocampal volume is associated with increased inflammation and more severe PTSD symptoms in veterans (O'Donovan et al, 2015a).”

    From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as O'Donovan et al, 2015a

    The Results and Discussion report that higher sTNF-RII was associated with reduced hippocampal volume and, separately, with more severe PTSD symptoms in Gulf War veterans. They do not establish that reduced hippocampal volume itself was associated with greater PTSD symptom severity, as the citing sentence implies. (LLM, conf=0.83)

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Authors
O’Donovan, A., Chao, L. L., Paulson, J., Samuelson, K. W., Shigenaga, J. K., Grunfeld, C., Weiner, M. W., & Neylan, T. C.
Affiliations
  • San Francisco VA Medical Center (US)
  • Alliant University (US)
Corresponding author
O’Donovan, Aoife
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2015-01
Volume
51
Pages
557-566
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2014.11.010
PMC
PMC4374733
OpenAlex
W2161017988
Cited by
86
References
16
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 9 · 2019: 5 · 2018: 14 · 2017: 11 · 2016: 10 · 2015: 3
FWCI
9.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Lightfighter Foundation, the US Army Military Operational Medicine Research Program, Department of Defense (W81XWH-11-2-0189)
  • National Institute on Aging (K24 AG031155)
  • National Center for Advancing Translational Sciences Career Development Award (KL2 TR000143)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
post-traumatic stress disorder, hippocampal volume, neuroinflammation, interleukin-6, soluble TNF receptor 2, Gulf War veterans, PTSD symptom severity, brain structure, neurogenesis, neurodegeneration
MeSH terms
Adult, Aged, Female, Hippocampus, Humans, Inflammation, Magnetic Resonance Imaging, Male, Middle Aged, Severity of Illness Index, Stress Disorders, Post-Traumatic, Veterans, Interleukin-6, Gulf War, Receptors, Tumor Necrosis Factor, Type II

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