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SYSTEMATIC REVIEW article

Front. Neurol.
Sec. Cognitive and Behavioral Neurology
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1500667
This article is part of the Research Topic Innovations in the assessment and treatment of TBI and co-occurring conditions in military connected populations View all articles

Gene c and peripheral biomarkers of comorbid pos rauma c stress disorder and trauma c brain injury: a systema c review

Provisionally accepted
Kiriana Cowansage Kiriana Cowansage 1Reshmi Nair Reshmi Nair 1Jose M. Lara-Ruiz Jose M. Lara-Ruiz 1Daniel E. Berman Daniel E. Berman 1Courtney C. Boyd Courtney C. Boyd 1Tiffany L. Milligan Tiffany L. Milligan 1Daniel Kotzab Daniel Kotzab 1Dawn M. Bellanti Dawn M. Bellanti 1Lisa M. Shank Lisa M. Shank 1Maria A. Morgan Maria A. Morgan 1Derek J. Smolenski Derek J. Smolenski 1Ida Babakhanyan Ida Babakhanyan 2Nancy A. Skopp Nancy A. Skopp 1Daniel P. Evatt Daniel P. Evatt 1Marija S. Kelber Marija S. Kelber 1*
  • 1 Psychological Health Center of Excellence, Defense Health Agency, Silver Spring, United States
  • 2 Traumatic Brain Injury Center of Excellence, Defense Health Agency, Silver Spring, United States

The final, formatted version of the article will be published soon.

    Background: Posttraumatic stress disorder (PTSD) commonly cooccurs with traumatic brain injury (TBI) in military populations and is a significant predictor of poor long-term outcomes; however, it is unclear to what extent specific biological variables are associated with comorbidity. This PROSPERO-registered systematic review evaluates the current body of literature on genetic and peripheral biomarkers associated with comorbid TBI and PTSD. Methods: Searches were conducted in four databases (PubMed, PsycInfo, PTSDPubs, Scopus). We included published studies examining differences in peripheral biomarkers among civilian, military, and veteran participants with both TBI and PTSD compared to those with TBI alone as well as, in some cases, PTSD alone and healthy controls. Data were extracted from included studies and evidence quality was assessed. Results: Our final analysis included 16 studies, the majority of which were based on data from active duty military and veteran participants. The results suggest that multiple gene variants are likely to contribute to the cumulative risk of PTSD comorbid with TBI. An elevated circulating level of the pro-inflammatory cytokine IL-6 was the most consistently replicated blood-based indicator of comorbid illness, compared to mTBI alone. Conclusion: Several genetic and protein markers of cellular injury and inflammation appear to be promising indicators of chronic pathology in comorbid TBI and PTSD. Additional research is needed to determine how such factors indicate, predict, and contribute to comorbidity and to what extent they represent viable targets for the development of novel diagnostic tools and therapeutic interventions.

    Keywords: biomarker, PTSD, TBI, military, veteran, neurodegeneration, genetic, Inflammation

    Received: 23 Sep 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Cowansage, Nair, Lara-Ruiz, Berman, Boyd, Milligan, Kotzab, Bellanti, Shank, Morgan, Smolenski, Babakhanyan, Skopp, Evatt and Kelber. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Marija S. Kelber, Psychological Health Center of Excellence, Defense Health Agency, Silver Spring, United States

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