Blast-related traumatic brain injury (bTBI) poses a significant concern for military personnel engaged in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). Given the highly stressful context in which such injury occurs, psychiatric comorbidities are common. This paper provides an overview of mild bTBI and discusses the cognitive sequelae and course of recovery typical of mild TBI (mTBI). Complicating factors that arise in the context of co-morbid posttraumatic stress disorder (PTSD) are considered with regard to diagnosis and treatment. Relatively few studies have evaluated the efficacy of cognitive rehabilitation in civilian mTBI, but we discuss cognitive training approaches that hold promise for addressing mild impairments in executive function and memory, akin to those seen in OEF/OIF veterans with bTBI and PTSD. Further research is needed to address the patient and environmental characteristics associated with optimal treatment outcome.
Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI−LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.
In: Logue , M W , Miller , M W , Wolf , E J , Huber , B R , Morrison , F G , Zhou , Z , Zheng , Y , Smith , A K , Daskalakis , N P , Ratanatharathorn , A , Uddin , M , Nievergelt , C M , Ashley-Koch , A E , Baker , D G , Beckham , J C , Garrett , M E , Boks , M P , Geuze , E , Grant , G A , Hauser , M A , Kessler , R C , Kimbrel , N A , Maihofer , A X , Marx , C E , Qin , X-J , Risbrough , V B , Rutten , B P F , Stein , M B , Ursano , R J , Vermetten , E , Vinkers , C H , Ware , E B , Stone , A , Schichman , S A , McGlinchey , R E , Milberg , W P , Hayes , J P , Verfaellie , M & Traumatic Stress Brain Study Group 2020 , ' An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci ' , Clinical epigenetics , vol. 12 , no. 1 , 46 . https://doi.org/10.1186/s13148-020-0820-0
Background Previous studies using candidate gene and genome-wide approaches have identified epigenetic changes in DNA methylation (DNAm) associated with posttraumatic stress disorder (PTSD). Methods In this study, we performed an EWAS of PTSD in a cohort of Veterans (n = 378 lifetime PTSD cases and 135 controls) from the Translational Research Center for TBI and Stress Disorders (TRACTS) cohort assessed using the Illumina EPIC Methylation BeadChip which assesses DNAm at more than 850,000 sites throughout the genome. Our model included covariates for ancestry, cell heterogeneity, sex, age, and a smoking score based on DNAm at 39 smoking-associated CpGs. We also examined in EPIC-based DNAm data generated from pre-frontal cortex (PFC) tissue from the National PTSD Brain Bank (n = 72). Results The analysis of blood samples yielded one genome-wide significant association with PTSD at cg19534438 in the gene G0S2 (p = 1.19 x 10(-7), p(adj) = 0.048). This association was replicated in an independent PGC-PTSD-EWAS consortium meta-analysis of military cohorts (p = 0.0024). We also observed association with the smoking-related locus cg05575921 in AHRR despite inclusion of a methylation-based smoking score covariate (p = 9.16 x 10(-6)), which replicates a previously observed PGC-PTSD-EWAS association (Smith et al. 2019), and yields evidence consistent with a smoking-independent effect. The top 100 EWAS loci were then examined in the PFC data. One of the blood-based PTSD loci, cg04130728 in CHST11, which was in the top 10 loci in blood, but which was not genome-wide significant, was significantly associated with PTSD in brain tissue (in blood p = 1.19 x 10(-5), p(adj) = 0.60, in brain, p = 0.00032 with the same direction of effect). Gene set enrichment analysis of the top 500 EWAS loci yielded several significant overlapping GO terms involved in pathogen response, including "Response to lipopolysaccharide" (p = 6.97 x 10(-6), p(adj) = 0.042). Conclusions The cross replication observed in independent cohorts is evidence that ...