Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review

BackgroundPosttraumatic 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-reg...

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Main Authors: Kiriana Cowansage, Reshmi Nair, Jose M. Lara-Ruiz, Daniel E. Berman, Courtney C. Boyd, Tiffany L. Milligan, Daniel Kotzab, Dawn M. Bellanti, Lisa M. Shank, Maria A. Morgan, Derek J. Smolenski, Ida Babakhanyan, Nancy A. Skopp, Daniel P. Evatt, Marija S. Kelber
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1500667/full
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author Kiriana Cowansage
Reshmi Nair
Jose M. Lara-Ruiz
Daniel E. Berman
Courtney C. Boyd
Tiffany L. Milligan
Daniel Kotzab
Dawn M. Bellanti
Lisa M. Shank
Maria A. Morgan
Derek J. Smolenski
Ida Babakhanyan
Nancy A. Skopp
Daniel P. Evatt
Marija S. Kelber
author_facet Kiriana Cowansage
Reshmi Nair
Jose M. Lara-Ruiz
Daniel E. Berman
Courtney C. Boyd
Tiffany L. Milligan
Daniel Kotzab
Dawn M. Bellanti
Lisa M. Shank
Maria A. Morgan
Derek J. Smolenski
Ida Babakhanyan
Nancy A. Skopp
Daniel P. Evatt
Marija S. Kelber
author_sort Kiriana Cowansage
collection DOAJ
description BackgroundPosttraumatic 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.MethodsSearches 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.ResultsOur 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.ConclusionSeveral 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.
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spelling doaj-art-a273eebed181487d91cc6f77e1aa87952025-01-27T05:14:30ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-01-011610.3389/fneur.2025.15006671500667Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic reviewKiriana Cowansage0Reshmi Nair1Jose M. Lara-Ruiz2Daniel E. Berman3Courtney C. Boyd4Tiffany L. Milligan5Daniel Kotzab6Dawn M. Bellanti7Lisa M. Shank8Maria A. Morgan9Derek J. Smolenski10Ida Babakhanyan11Nancy A. Skopp12Daniel P. Evatt13Marija S. Kelber14Psychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesTraumatic Brain Injury Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesPsychological Health Center of Excellence, Defense Health Agency, Falls Church, VA, United StatesBackgroundPosttraumatic 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.MethodsSearches 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.ResultsOur 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.ConclusionSeveral 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.https://www.frontiersin.org/articles/10.3389/fneur.2025.1500667/fullbiomarkerPTSDTBImilitaryveteranneurodegeneration
spellingShingle Kiriana Cowansage
Reshmi Nair
Jose M. Lara-Ruiz
Daniel E. Berman
Courtney C. Boyd
Tiffany L. Milligan
Daniel Kotzab
Dawn M. Bellanti
Lisa M. Shank
Maria A. Morgan
Derek J. Smolenski
Ida Babakhanyan
Nancy A. Skopp
Daniel P. Evatt
Marija S. Kelber
Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
Frontiers in Neurology
biomarker
PTSD
TBI
military
veteran
neurodegeneration
title Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
title_full Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
title_fullStr Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
title_full_unstemmed Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
title_short Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review
title_sort genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury a systematic review
topic biomarker
PTSD
TBI
military
veteran
neurodegeneration
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1500667/full
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