Dataset Information

Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

ABSTRACT: BACKGROUND:Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph-based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls. METHODS:102 participants with (n=50) or without PTSD (n=52) completed functional magnetic resonance imaging (fMRI) at rest and during symptom provocation using subject-specific script imagery. Vertex/voxel global brain connectivity with global signal regression (GBCr), a measure of nodal strength, was calculated as the average of its functional connectivity with all other vertices/voxels in the brain gray matter. RESULTS:In contrast to during resting-state, where there were no group differences, we found a significantly higher GBCr during symptom provocation, in PTSD participants compared to controls, in areas within the right hemisphere, including anterior insula, caudal-ventrolateral prefrontal, and rostral-ventrolateral parietal cortices. Overall, these clusters overlapped with the ventral and dorsal salience networks. Post hoc analysis showed increased GBCr in these salience clusters during symptom provocation compared to resting-state. In addition, resting-state GBCr in the salience clusters predicted GBCr during symptom provocation in PTSD participants but not in controls. CONCLUSION:In PTSD, increased connectivity within the salience network has been previously hypothesized, based primarily on seed-based connectivity findings. The current results strongly support this hypothesis using whole-brain network measure in a fully data-driven approach. It remains to be seen in future studies whether these identified salience disturbances would normalize following treatment.

SUBMITTER: Abdallah CG

PROVIDER: S-EPMC6529942 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

Abdallah Chadi G CG Averill Christopher L CL Ramage Amy E AE Averill Lynnette A LA Goktas Selin S Nemati Samaneh S Krystal John H JH Roache John D JD Resick Patricia A PA Young-McCaughan Stacey S Peterson Alan L AL Fox Peter P

Chronic stress (Thousand Oaks, Calif.) 20190101

<h4>Background</h4>Better understanding of the neurobiology of posttraumatic stress disorder (PTSD) may be critical to developing novel, effective therapeutics. Here, we conducted a data-driven investigation using a well-established, graph-based topological measure of nodal strength to determine the extent of functional dysconnectivity in a cohort of active duty US Army soldiers with PTSD compared to controls.<h4>Methods</h4>102 participants with (n=50) or without PTSD (n=52) completed functiona ...[more]

PMID: 31131337

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Project description:ImportancePosttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity.ObjectiveTo discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).Design, setting, and participantsTwo coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique participants with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique participants with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015.Main outcomes and measuresAssociation analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated.ResultsThe NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10-8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10-8) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10-8) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism-based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis.Conclusions and relevanceIn the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55-associated in prior research with several autoimmune and inflammatory disorders-and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.

Project description:Studies have suggested that sickle cell trait elevates the risks of exertional rhabdomyolysis and death. We conducted a study of sickle cell trait in relation to these outcomes, controlling for known risk factors for exertional rhabdomyolysis, in a large population of active persons who had undergone laboratory tests for hemoglobin AS (HbAS) and who were subject to exertional-injury precautions.We used Cox proportional-hazards models to test whether the risks of exertional rhabdomyolysis and death varied according to sickle cell trait status among 47,944 black soldiers who had undergone testing for HbAS and who were on active duty in the U.S. Army between January 2011 and December 2014. We used the Stanford Military Data Repository, which contains comprehensive medical and administrative data on all active-duty soldiers.There was no significant difference in the risk of death among soldiers with sickle cell trait, as compared with those without the trait (hazard ratio, 0.99; 95% confidence interval [CI], 0.46 to 2.13; P=0.97), but the trait was associated with a significantly higher adjusted risk of exertional rhabdomyolysis (hazard ratio, 1.54; 95% CI, 1.12 to 2.12; P=0.008). This effect was similar in magnitude to that associated with tobacco use, as compared with no use (hazard ratio, 1.54; 95% CI, 1.23 to 1.94; P<0.001), and to that associated with having a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30.0 or more, as compared with a BMI of less than 25.0 (hazard ratio, 1.39; 95% CI, 1.04 to 1.86; P=0.03). The effect was less than that associated with recent use of a statin, as compared with no use (hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P=0.001), or an antipsychotic agent (hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P=0.008).Sickle cell trait was not associated with a higher risk of death than absence of the trait, but it was associated with a significantly higher risk of exertional rhabdomyolysis. (Funded by the National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences.).

Project description:IntroductionUnderstanding how soldiers die after separation from military service, particularly those who die shortly after separating from service, may help to identify opportunities to ease transitions to civilian life.Materials and methodsMortality data were analyzed for male U.S. Army soldiers who died within 18 months of their separation from service (from 1999 to 2011). Descriptive statistics were calculated for natural, accidental, suicidal, homicidal, undetermined, and legal/operation of war deaths and were stratified by age, component, time in service, and type of discharge. Crude and age-adjusted mortality rates, standardized for all years using the 2004 Regular Army population, were also calculated. The Public Health Review Board of the U.S. Army Public Health Center approved this study as Public Health Practice.ResultsOf the 1,884,653 male soldiers who separated from service during the study period, 3,819 died within 18 months of separation. A majority of all separations were Reserve or National Guard (58%), and 62% of decedents were in the Reserve or National Guard. Deaths from natural causes (38%) were the most common, followed by accident deaths (34%), suicides (20%), homicides (6%), undetermined deaths (2%), and legal/operation of war deaths (<1%). For overall mortality, age-adjusted rates were higher among the male U.S. population when compared to male soldiers who had separated from the Army.ConclusionsThe time period immediately following separation from the Army presents a unique challenge for many soldiers. Developing more effective pre-separation prevention programs that target specific risks requires knowing the causes of death for natural deaths, suicides, and accidents. Over half of all deaths occurring shortly after separation from service are preventable. Continued surveillance of specific causes of preventable deaths following separation can improve pre-separation prevention programs and transitions to post-service care.

Project description:BackgroundAlthough the majority of active duty U.S. Army soldiers are full-time personnel in the Active Component (AC), a substantial minority of soldiers on active duty are in the Reserve Components (RCs). These "citizen-soldiers" (Army National Guard and Army Reserve) represent a force available for rapid activation in times of national need. RC soldiers experience many of the same stressors as AC soldiers as well as stressors that are unique to their intermittent service. Despite the important role of RC soldiers, the vast majority of military mental health research focuses on AC soldiers. One important goal of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is to address this gap. Here we examine predictors of suicide attempts among activated RC soldiers.MethodsThis longitudinal, retrospective cohort study used individual-level person-month records from Army and Department of Defense administrative data systems to examine socio-demographic, service-related, and mental health predictors of medically documented suicide attempts among activated RC soldiers during 2004-2009. Data from all 1103 activated RC suicide attempters and an equal-probability sample of 69,867 control person-months were analyzed using a discrete-time survival framework.ResultsEnlisted soldiers comprised 84.3% of activated RC soldiers and accounted for 95.7% of all activated RC suicide attempts (overall rate = 108/100,000 person-years, more than four times the rate among officers). Multivariable predictors of enlisted RC suicide attempts included being female, entering Army service at age ≥ 25, current age < 30, non-Hispanic white, less than high school education, currently married, having 1-2 years of service, being previously deployed (vs. currently deployed), and history of mental health diagnosis (particularly when documented in the previous month). Predictors among RC officers (overall rate = 26/100,000 person-years) included being female and receiving a mental health diagnosis in the previous month. Discrete-time hazard models showed suicide attempt risk among enlisted soldiers was inversely associated with time in service.ConclusionsRisk factors for suicide attempt in the RCs were similar to those previously observed in the AC, highlighting the importance of research and prevention focused on RC enlisted soldiers in the early phases of Army service and those with a recent mental health diagnosis.

Project description:IntroductionIdentification of modifiable risk factors for suicidal behaviors is a priority for the U.S. Army. This study investigated associations of nicotine dependence with suicidal behaviors among incoming soldiers.MethodsLifetime DSM-IV nicotine dependence, mental disorders, suicidal behaviors, and their ages of onset were retrospectively assessed in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study. Discrete-time survival analysis of person-year data from 30,436 soldiers was performed to evaluate associations of nicotine dependence with subsequent suicidal ideation, plans, and attempts. Among respondents with lifetime ideation (n=4,060), models tested associations of nicotine dependence with progression from ideation to first onset of plan, from plan to first attempt, and, among ideators without plans, from ideation to first unplanned attempt. A hierarchy of models incorporated increasing controls for other risk factors. Data were collected in 2011-2012 and analyzed in 2017-2018.ResultsIn models controlling for sociodemographic characteristics, nicotine dependence was associated with onset of all suicidal behaviors (AORs, 2.07-4.08, p<0.001) and with each type of progression of suicidal behavior (AORs, 1.48-2.44, p<0.005). After adjusting for childhood adversities and mental disorders, nicotine dependence remained associated with onset of ideation (AOR=1.27, 95% CI=1.10, 1.46, p=0.001) and attempt (AOR=1.83, 95% CI=1.41, 2.37, p<0.001); and with progression from ideation to unplanned attempt (AOR=2.03, 95% CI=1.17, 1.74, p<0.001).ConclusionsNicotine dependence exhibited associations with onset of suicidal ideation and suicide attempt-and with progression from ideation to unplanned attempt-that were independent of other measured risk factors. Awareness of associations of nicotine dependence with suicidal behaviors may inform risk assessment, facilitate targeting of prevention efforts, and provide further impetus for reducing nicotine dependence.

Dataset Information

Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

Publications

Salience Network Disruption in U.S. Army Soldiers With Posttraumatic Stress Disorder.

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