Dataset Information

APOE-ε4 Genotype is Associated with Elevated Post-Concussion Symptoms in Military Veterans with a Remote History of Mild Traumatic Brain Injury.

ABSTRACT:

Objective

We evaluated the influence of the APOE-ε4 allele on post-concussive symptoms in military Veterans with a remote history of mild traumatic brain injury (mTBI).

Method

Participants (N = 77) were administered neuropsychiatric measures, on average, approximately 5 years following their most recent mTBI and provided a DNA sample for APOE genotyping. Veterans were divided into two groups based on their ε4 status (n = 14 ε4+, n = 63 ε4-). The Neurobehavioral Symptom Inventory (NSI) was the primary outcome measure, from which a total score was derived, as well as three symptom clusters (somatic, cognitive, and affective).

Results

ANCOVAs showed a significant main effect of ε4 genotype on the NSI total score and somatic symptom cluster after adjusting for posttraumatic stress symptoms and mTBI history (p = .019-.028, ηp2 = .064-.073), such that ε4+ Veterans endorsed significantly greater symptoms than ε4- Veterans.

Conclusions

Our findings suggest that genetic risk may help to explain the poorer long-term outcomes often observed in this population.

SUBMITTER: Merritt VC

PROVIDER: S-EPMC6659168 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

APOE-ε4 Genotype is Associated with Elevated Post-Concussion Symptoms in Military Veterans with a Remote History of Mild Traumatic Brain Injury.

Merritt Victoria C VC Lapira Kristina M KM Clark Alexandra L AL Sorg Scott F SF Werhane Madeleine L ML Jak Amy J AJ Bondi Mark W MW Schiehser Dawn M DM Delano-Wood Lisa L

Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists 20190701 5

<h4>Objective</h4>We evaluated the influence of the APOE-ε4 allele on post-concussive symptoms in military Veterans with a remote history of mild traumatic brain injury (mTBI).<h4>Method</h4>Participants (N = 77) were administered neuropsychiatric measures, on average, approximately 5 years following their most recent mTBI and provided a DNA sample for APOE genotyping. Veterans were divided into two groups based on their ε4 status (n = 14 ε4+, n = 63 ε4-). The Neurobehavioral Symptom Inventory ( ...[more]

PMID: 30521018

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Project description:As few studies have examined the relationship between the apolipoprotein E (APOE) gene and clinical outcomes after military-related traumatic brain injury (TBI), we aimed to determine whether the ?4 allele of the APOE gene influences neuropsychiatric symptoms in veterans with a history of mild-to-moderate TBI. Participants included 133 veterans (TBI?=?79; military controls [MC]?=?54) who underwent APOE genotyping and were divided into ?4+ (TBI?=?18; MC?=?15) and ?4- (TBI?=?61; MC?=?39) groups. All participants underwent evaluation of psychological distress using the Beck Depression Inventory-II, Beck Anxiety Inventory, and PTSD Checklist-Military Version. Two-way analyses of variance were conducted to examine the effect of group (TBI vs. MC) and APOE-?4 status (?4+ vs. ?4-) across symptom measures. There was a significant main effect of group across all symptom measures (TBI > MC; all p values <0.001), no main effect of ?4 genotype (p?=?0.152-0.222), and a significant interaction of group by ?4 genotype across all measures (p?=?0.027-0.047). Specifically, for TBI participants, ?4+ veterans demonstrated significantly higher symptom scores across all measures when compared to ?4- veterans (p?=?0.007-0.015). For MC participants, ?4 status had no effect on the severity of psychiatric symptom scores (p?=?0.585-0.708). Our results demonstrate that, in our well-characterized sample of veterans with history of neurotrauma, possession of the ?4 allele conveys risk for increased symptomatology (i.e., depression, anxiety, and post-traumatic stress disorder), even well outside of the acute phase of injury. Findings suggest a meaningful relationship between APOE genotype and psychiatric distress post-TBI, and they suggest that there is a brain basis for the complex neuropsychiatric presentation often observed in this vulnerable population. Future longitudinal studies are needed in order to further our understanding of how genetic factors influence response to TBI.

Project description:ImportanceTraumatic brain injury (TBI) is common in both veteran and civilian populations. Prior studies have linked moderate and severe TBI with increased dementia risk, but the association between dementia and mild TBI, particularly mild TBI without loss of consciousness (LOC), remains unclear.ObjectiveTo examine the association between TBI severity, LOC, and dementia diagnosis in veterans.Design, setting, and participantsThis cohort study of all patients diagnosed with a TBI in the Veterans Health Administration health care system from October 1, 2001, to September 30, 2014, and a propensity-matched comparison group. Patients with dementia at baseline were excluded. Researchers identified TBIs through the Comprehensive TBI Evaluation database, which is restricted to Iraq and Afghanistan veterans, and the National Patient Care Database, which includes veterans of all eras. The severity of each TBI was based on the most severe injury recorded and classified as mild without LOC, mild with LOC, mild with LOC status unknown, or moderate or severe using Department of Defense or Defense and Veterans Brain Injury Center criteria. International Classification of Diseases, Ninth Revision codes were used to identify dementia diagnoses during follow-up and medical and psychiatric comorbidities in the 2 years prior to the index date.Main outcomes and measuresDementia diagnosis in veterans who had experienced TBI with or without LOC and control participants without TBI exposure.ResultsThe study included 178 779 patients diagnosed with a TBI in the Veterans Health Administration health care system and 178 779 patients in a propensity-matched comparison group. Veterans had a mean (SD) age of nearly 49.5 (18.2) years at baseline; 33 250 (9.3%) were women, and 259 136 (72.5%) were non-Hispanic white individuals. Differences between veterans with and without TBI were small. A total of 4698 veterans (2.6%) without TBI developed dementia compared with 10 835 (6.1%) of those with TBI. After adjustment for demographics and medical and psychiatric comobidities, adjusted hazard ratios for dementia were 2.36 (95% CI, 2.10-2.66) for mild TBI without LOC, 2.51 (95% CI, 2.29-2.76) for mild TBI with LOC, 3.19 (95% CI, 3.05-3.33) for mild TBI with LOC status unknown, and 3.77 (95% CI, 3.63-3.91) for moderate to severe TBI.Conclusions and relevanceIn this cohort study of more than 350 000 veterans, even mild TBI without LOC was associated with more than a 2-fold increase in the risk of dementia diagnosis. Studies of strategies to determine mechanisms, prevention, and treatment of TBI-related dementia in veterans are urgently needed.

Dataset Information

APOE-ε4 Genotype is Associated with Elevated Post-Concussion Symptoms in Military Veterans with a Remote History of Mild Traumatic Brain Injury.

Objective

Method

Results

Conclusions

Publications

APOE-ε4 Genotype is Associated with Elevated Post-Concussion Symptoms in Military Veterans with a Remote History of Mild Traumatic Brain Injury.

Similar Datasets

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