Dataset Information

Apolipoprotein E ?4 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury.

ABSTRACT: 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.

SUBMITTER: Merritt VC

PROVIDER: S-EPMC6157345 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Apolipoprotein E ε4 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury.

Merritt Victoria C VC Clark Alexandra L AL Sorg Scott F SF Evangelista Nicole D ND Werhane Madeleine M Bondi Mark W MW Schiehser Dawn M DM Delano-Wood Lisa L

Journal of neurotrauma 20180607 19

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 ε4 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 ε4<sup>+</sup> (TBI = 18; MC = 15) and ε4<sup>-</sup> (TBI = ...[more]

PMID: 29463164

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Project description:A history of traumatic brain injury (TBI) increases the odds of developing Alzheimer's disease (AD). The long latent period between injury and dementia makes it difficult to study molecular changes initiated by TBI that may increase the risk of developing AD. MicroRNA (miRNA) levels are altered in TBI at acute times post-injury (<4 weeks), and in AD. We hypothesized that miRNA levels in cerebrospinal fluid (CSF) following TBI in veterans may be indicative of increased risk for developing AD. Our population of interest is cognitively normal veterans with a history of one or more mild TBI (mTBI) at a chronic time following TBI. We measured miRNA levels in CSF from three groups of participants: (1) community controls with no lifetime history of TBI (ComC); (2) deployed Iraq/Afghanistan veterans with no lifetime history of TBI (DepC), and (3) deployed Iraq/Afghanistan veterans with a history of repetitive blast mTBI (DepTBI). CSF samples were collected at the baseline visit in a longitudinal, multimodal assessment of Gulf War veterans, and represent a heterogenous group of male veterans and community controls. The average time since the last blast mTBI experienced was 4.7 ± 2.2 years [1.5 - 11.5]. Statistical analysis of TaqManTM miRNA array data revealed 18 miRNAs with significant differential expression in the group comparisons: 10 between DepTBI and ComC, 7 between DepC and ComC, and 8 between DepTBI and DepC. We also identified 8 miRNAs with significant differential detection in the group comparisons: 5 in DepTBI vs. ComC, 3 in DepC vs. ComC, and 2 in DepTBI vs. DepC. When we applied our previously developed multivariable dependence analysis, we found 13 miRNAs (6 of which are altered in levels or detection) that show dependencies with participant phenotypes, e.g., ApoE. Target prediction and pathway analysis with miRNAs differentially expressed in DepTBI vs. either DepC or ComC identified canonical pathways highly relevant to TBI including senescence and ephrin receptor signaling, respectively. This study shows that both TBI and deployment result in persistent changes in CSF miRNA levels that are relevant to known miRNA-mediated AD pathology, and which may reflect early events in AD.

Project description:BackgroundHeadache (HA) is a common persistent complaint following mild traumatic brain injury (mTBI), but the association with remote mTBI is not well established, and risk factors are understudied.ObjectiveDetermine the relationship of mTBI history and other factors with HA prevalence and impact among combat-exposed current and former service members (SMs).DesignSecondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study.MethodsWe examined the association of lifetime mTBI history, demographic, military, medical and psychosocial factors with (1) HA prevalence ("lately, have you experienced headaches?") using logistic regression and (2) HA burden via the Headache Impact Test-6 (HIT-6) using linear regression. Each lifetime mTBI was categorized by mechanism (blast-related or not) and setting (combat deployed or not). Participants with non-credible symptom reporting were excluded, leaving N = 1,685 of whom 81% had positive mTBI histories.ResultsAt a median 10 years since last mTBI, mTBI positive participants had higher HA prevalence (69% overall, 78% if 3 or more mTBIs) and greater HA burden (67% substantial/severe impact) than non-TBI controls (46% prevalence, 54% substantial/severe impact). In covariate-adjusted analysis, HA prevalence was higher with greater number of blast-related mTBIs (OR 1.81; 95% CI 1.48, 2.23), non-blast mTBIs while deployed (OR 1.42; 95% CI 1.14, 1.79), or non-blast mTBIs when not deployed (OR 1.23; 95% CI 1.02, 1.49). HA impact was only higher with blast-related mTBIs. Female identity, younger age, PTSD symptoms, and subjective sleep quality showed effects in both prevalence and impact models, with the largest mean HIT-6 elevation for PTSD symptoms. Additionally, combat deployment duration and depression symptoms were factors for HA prevalence, and Black race and Hispanic/Latino ethnicity were factors for HA impact. In sensitivity analyses, time since last mTBI and early HA onset were both non-significant.ConclusionThe prevalence of HA symptoms among formerly combat-deployed veterans and SMs is higher with more lifetime mTBIs regardless of how remote. Blast-related mTBI raises the risk the most and is uniquely associated with elevated HA burden. Other demographic and potentially modifiable risk factors were identified that may inform clinical care.

Dataset Information

Apolipoprotein E ?4 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury.

Publications

Apolipoprotein E ε4 Genotype Is Associated with Elevated Psychiatric Distress in Veterans with a History of Mild to Moderate Traumatic Brain Injury.

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