STRESS AND RESILIENCY IN U.S. ARMY MORTUARY AFFAIRS SOLDIERS
U.S. Army mortuary affairs (MA) soldiers work with the remains of the dead and are exposed to one of the highest stressors of war, combat death.
Research focused on the stresses of MA work since 2005. MA detachments that deployed to the Middle East completed pre- and post-deployment surveys assessing factors such as: PTSD and post-traumatic stress symptoms, depression, somatization, anger, hostility, and health risk behaviors (e.g. increases in alcohol, tobacco, and drug use). In addition, this study examines soldier resilience, psychological well-being, instrumental and emotional support, identification with the dead, and mutilation fear (responses to blood, injury, and mutilation). To date, over 2,900 surveys have been collected.
While the majority of soldiers who have participated in the study have completed one or two surveys, some soldiers have completed as many as 8 surveys, providing the unique opportunity to examine stress and resilience in soldiers over time. New in 2017, saliva samples were collected along with survey data. The genetic DNA and RNA material in saliva will be analyzed for potential biological markers of PTSD, stress, and resilience. Importantly, objective measures of DNA and RNA biomarkers to the subjective survey measures of stress and resilience will be compared. This study has implications for early intervention, training, education, leadership, and health surveillance.
THE NATIONAL MILITARY FAMILY BEREAVEMENT STUDY (NMFBS)
The goal of the study is to build upon the robust civilian research literature on bereavement and its impact on survivors — how psychological, physical and/or behavioral outcomes of the grieving process are influenced by family members’ pre-existing psychological and physical health, social and grief support, and military-specific factors in the population of service members who have died since 9/11.
The longitudinal portion of the study, which consisted of annual interviews over a three-year period, was completed in 2017. Approximately 850 adults and 120 children completed the longitudinal portion of the study, and 981 participants provided saliva samples for analysis of genetic biomarkers associated with bereavement-related outcomes.
Findings from the study have informed ongoing discussion to define appropriate diagnostic criteria for a condition of impairing grief. As a result of this groundbreaking work, CSTS has partnered with colleagues at Columbia University, New York University, University of Pittsburgh, and the University of California San Diego in developing a proposal for alternate and more clinically-relevant criteria of a persistent grief disorder to be included in future editions of the Diagnostic and Statistical Manual.
Scientists published two scientific manuscripts and gave several presentations regarding findings from NMFBS at national conferences.
BIOMARKER RESEARCH: FKBP5 SNPS WITH PTSD
Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with a prevalence of more than 7% in the US population and 12% in the military. FKBP5, a glucocorticoid-regulated immunophilin, is thought to be associated with PTSD. However, how it works is unknown.
We have used blood samples from service members (n=3890) and cell cultures to study FKBP5 in PTSD. We found that FKBP5 gene is associated with lifetime PTSD in soldiers and FKBP5 plays an important role in mitochondria in stress response. Findings indicate that traumatic stress responses are mediated by FKBP5, a glucocorticoid-regulated immunophilin. Four single-nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, rs9470080) covering the FKBP5 gene are associated with lifetime PTSD in Soldiers. Up-regulated FKBP5 and significantly increased cortisol levels were observed in the Soldiers with PTSD.
Using an in vitro simulated traumatic situation, scientists found that exposure to a stress hormone results in a redistribution of FKBP5 to mitochondria and concomitant increases of mitochondrial membrane potential and ROS production in the human cell line. The FKBP5 inhibitor FK506 pharmacologically attenuates the effects of the stress hormone, indicating that FKBP5 regulation of mitochondrial function is necessary. Further data shows that more FKBP5 co-localizes with the mitochondria in leukocytes of PTSD subjects compared to controls without PTSD. Additional findings indicate significant down-regulation of mitochondrial complexes I, II, and III in PTSD subjects compared to non-PTSD controls, supporting concerns for mitochondrial dysfunction in the disorder. Current research provides evidence showing that FKBP5 is associated with PTSD and that dysfunction of mitochondria might play a role in the pathology of PTSD and be a promising drug target for PTSD.
THE BRAIN INDICES STUDY
The goal of the Brain Indices Study is to develop reliable and valid predictors of negative outcomes to inform targeted treatments that can be implemented early, and thereby improve the lives of our wounded warriors and their families. The study, funded by the DoD Congressionally Directed Medical Research Programs (CDMRP) and the Center for Neuroscience and Regenerative Medicine (CNRM), was conducted in the Brain Assessment Research Laboratories at WRNMMC and Fort Belvoir Community Hospital. This longitudinal study was designed to identify measures of brain structure and function that predict PTSD and other deleterious outcomes in Service members with mTBI.
The assessment battery of the Brain Indices study, which comprised neuroimaging (structural MRI/DTI), electrophysiological, neurocognitive, and neurological assessments, was administered soon after injury, and 3 and 6 months later. The outcome measures included interviews for PTSD, depression, and headache, as well as post-concussive symptoms and overall mental and physical health status.
Since the completion of data collection, CSTS efforts have been directed to quality assurance, data processing and analysis, and preparation of manuscripts.
THE CHRONIC EFFECTS OF NEUROTRAUMA CONSORTIUM STUDY 1: OBSERVATIONAL STUDY ON LATE NEUROLOGIC EFFECTS OF OEF/OIF/OND COMBAT
This is a longitudinal, multisite consortium investigation, funded by the DoD CDMRP, aimed at evaluation of the chronic sequelae and comorbidities associated with TBI. An extensive battery of physiological, psychological, neurocognitive, occupational, and social functioning measures is administered to Service members and veterans who sustained TBI in OEF/OIF/OND. Participants undergo periodic in-person and telephone reassessments to monitor their overall status. CSTS directs the electrophysiological (event-related brain potentials and EEG) component of this study, aimed at assessing sensory and cognitive function.
This longitudinal cohort will permit an evaluation of the post-TBI prevalence, natural history, and response to interventions of chronic symptoms and associated comorbidities. Cross-sectional data will allow for analysis of the effect of time post-injury on chronic symptoms, associated comorbidities, and evidence of neurodegeneration or recovery. Data collection is ongoing.
Application of Somatosensory Evoked Potentials to the Diagnosis of Traumatic Brain Injury (TBI): A Translational Approach
CSTS directs this FDA-funded study that aims to: (a) determine the utility of specific EEG biomarkers as diagnostic tools in Service members with blast-induced TBI based on translational work in animal (mouse) models; (b) use components of the somatosensory evoked potential (SEP) to assess neurosensory effects of brain injury; and (c) evaluate correlations between the magnitude of EEG changes and the severity of brain injury. This work is aimed at exploring the use of SEPs as an EEG biomarker for a field-deployable diagnostic for TBI. Data collection at WRNMMC is expected to commence in early 2018.
ECOLOGICAL MOMENTARY ASSESSMENT OF POSTTRAUMATIC STRESS SYMPTOMS IN U.S. MILITARY SERVICE MEMBERS (DAILY DIARY STUDY)
This study uses a cutting-edge methodology, ecological momentary assessment, to collect data from U.S. military Service members throughout the day on PTSD and post-traumatic stress symptoms (PTSS), depression, somatization, sleep, pain, substance use, psychosocial interactions and other areas of health and functioning. This “daily diary” methodology allows for detailed assessment of variability of symptom patterns as they occur throughout the Service member’s daily routine, providing important insights into the interaction between symptoms and environment, psychosocial relatedness and brain processes. Participants use electronic tablets to complete assessments four times per day over 15 continuous days.
Data is recorded and stored using a sophisticated application developed in collaboration with the National Center for Telehealth and Technology (T2) specifically for use in this study. This technology allows for more accurate data collection and real time evaluation. At baseline and at one and three month follow-ups, we collect a wide range of behavioral and psychological assessments including: disorders (e.g., PTSD, depression), distress (e.g., PTSS, sleep difficulties), health risk behaviors (alcohol, drug and tobacco use), and health care utilization. In addition, participants have the option to donate blood and/or saliva samples for genetic analysis to identify potential biomarkers and gene-environment interactions that may distinguish and/or mediate traumatic stress responses and resilience to stress-related disorders.
To date, 115 Service members have participated in the study. Data analyses in 2017 included examining daily variation in PTSS across days of the week and the relationship between hours of sleep and PTSS variation. We also are examining PTSD, depression, and daily caffeine and alcohol consumption.
In March, we presented our findings of daily variation in PTSS at the American Psychosomatic Society’s 75th Annual Scientific Meeting in Seville, Spain. In April, we presented a methodological poster exploring the error covariance structure in mixed model analyses at the Anxiety and Depression Association of America’s annual conference in San Francisco, CA. This innovative study has implications for interventions and program development through awareness of post-traumatic symptom variability. This methodology informs future use of technology in psychiatric assessment, treatment, and research.