Suchergebnisse

Abstract. Background: Suicide among veterans has increased in recent years, making the identification of those at greatest risk for self-injurious behavior a high research priority. Aims: We investigated whether affective impulsivity and risky behaviors distinguished typologies of self-injurious thoughts and behaviors in a sample of trauma-exposed veterans. Method: A total of 95 trauma-exposed veterans (ages 21–55; 87% men) completed self-report measures of self-injurious thoughts and behaviors, impulsivity, and clinical symptoms. Results: A latent profile analysis produced three classes that differed in suicidal ideation, suicide attempts and nonsuicidal self-injury (NSSI): A low class that reported little to no self-injurious thoughts or behaviors; a self-injurious thoughts (ST) class that endorsed high levels of ideation but no self-harm behaviors; and a self-injurious thoughts and behaviors (STaB) class that reported ideation, suicide attempts and NSSI. Membership in the STaB class was associated with greater affective impulsivity, disinhibition, and distress/arousal than the other two classes. Limitations: Limitations include an overrepresentation of males in our sample, the cross-sectional nature of the data, and reliance on self-report measures. Conclusion: Findings point to affective impulsivity and risky behaviors as important characteristics of veterans who engage in self-injurious behaviors.

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.

The frequent co-occurrence of antisocial behavior and other disinhibited phenotypes reflects a highly heritable externalizing spectrum. We examined the molecular genetic basis of this spectrum by testing polygenic associations with psychopathology symptoms, impulsive traits, and cognitive functions in two samples of primarily military veterans (n =537, n =194). We also investigated whether polygenic risk for externalizing moderated the effects of trauma on these phenotypes. As hypothesized, polygenic risk positively predicted externalizing psychopathology and negatively predicted performance on inhibitory control tasks. Gene-by-environment effects were also evident, with trauma exposure predicting greater impulsivity and less working memory capacity, but only at high levels of genetic liability. As expected, polygenic risk was not associated with internalizing psychopathology or episodic memory performance. This is the first independent replication of the polygenic score as a measure of genetic predispositions for externalizing and provides preliminary evidence that executive dysfunction is a heritable vulnerability for externalizing psychopathology.

AbstractBody mass index (BMI) is a risk factor for Alzheimer's disease (AD) although the relationship is complex. Obesity in midlife is associated with increased risk for AD, whereas evidence supports both higher and lower BMI increasing risk for AD in late life. This study examined the influence of individual differences in genetic risk for AD to further clarify the relationship between late-life BMI and conversion to AD. Participants included 52 individuals diagnosed as having mild cognitive impairment (MCI) at baseline who converted to AD within 24 months and 52 matched MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. BMI was measured at baseline. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Conditional logistic regression models were run to determine if BMI and polygenic risk predicted conversion to AD. Results showed an interaction between BMI and genetic risk, such that individuals with lower BMI and higher polygenic risk were more likely to convert to AD relative to individuals with higher BMI. These results remained significant after adjusting for cerebrospinal fluid biomarkers of AD. Exploratory sex-stratified analyses revealed this relationship only remained significant in males. These results show that higher genetic risk in the context of lower BMI predicts conversion to AD in the next 24 months, particularly among males. These findings suggest that genetic risk for AD in the context of lower BMI may serve as a prodromal risk factor for future conversion to AD.

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 ...

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population. The purpose of this manuscript is to describe both the challenges and opportunities when conducting military-relevant TBI research and introduce the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Military Brain Injury working group. ENIGMA is a worldwide consortium focused on improving replicability and analytical power through data sharing and collaboration. In this paper, we discuss challenges affecting efforts to aggregate data in this patient group. In addition, we highlight how "big data" approaches might be used to understand better the role that each of these variables might play in the imaging and functional phenotypes of TBI in Service member and Veteran populations, and how data may be used to examine important military specific issues such as return to duty, the late effects of combat-related injury, and alteration of the natural aging processes.