Active Research Projects focused on the health and mental health of service members and their families and children include:
Nightmares and insomnia are among the most prevalent refractory symptoms of posttraumatic stress disorder (PTSD). Current evidence-based treatments for PTSD, such as prolonged exposure and cognitive processing therapy, utilize fear memory extinction and reconsolidation but do not target sleep symptoms. Given that nightmares are thought to have an essential role in trauma memory maintenance, developing a treatment that activates trauma memory through exposure to nightmare images may facilitate trauma memory reconsolidation. This pilot trial is investigating Nightmare Deconstruction and Reprocessing (NDR), a three-stage treatment model that begins with exposure to nightmare images, moves to meaning-making and reprocessing, and then to nightmare reconstruction and rehearsal. In working toward our goal of conducting a large-scale randomized controlled trial, CSTS is partnering with Walter Reed National Military Medical Center, Naval Hospital Camp Pendleton, and the National Institutes of Health to pilot test NDR’s plausibility as a treatment for PTSD-related nightmares in military service members and to test the methodologic feasibility of integrating biomarkers as objective measures of treatment efficacy and tolerability, including actigraphic data, heart-rate variability, electrodermal conductance, and genomic and inflammatory markers. This study will begin recruiting participants in 2019.
The Center for the Study of Traumatic Stress, in collaboration with Dr. Sandro Galea of Boston University, is engaged in a nation-wide research project on the health and mental health of National Guard and Reserve Service members, an at risk population that has been understudied. The study addresses the epidemiology and the trajectory of posttraumatic stress, deployment stress, health risk behaviors and health care utilization in National Guard and Reserve. The fourth wave of data collection has been completed, and the combined team is actively working on data analysis, as well as preparing to conduct a fifth wave of data collection. Four publications have resulted from this research, and several more articles are under development.
Using blood samples from suicide attempters and non-attempters, and post-mortem brain tissue from patients who had committed suicide and non-suicide controls, Center for the Study of Traumatic Stress scientists examined levels of peripheral blood mononuclear cell (PBMC) p11 mRNA to determine how these levels might help differentiate between those individuals who would attempt or complete suicide versus those who would not. The results demonstrated for the first time that PMBC p11 mRNA level is a potential adjunctive biomarker for the assessment of suicide risk in mental disorders. The Center has continued to analyze data from the collections, with a focus identifying outcomes and biomarkers for our overall genetic analyses.
Veterans Affairs-Department of Defense PTSD Brain Tissue Biorepository
In 2015, a consortium led by the Department of Veterans Affairs National Center for PTSD and co-Founded by CSTS Scientists launched a PTSD brain tissue biorepository—or "brain bank"—to support research on the causes, progression and treatment of PTSD affecting Veterans.
The national brain bank will investigate the impact of stress, trauma and PTSD on brain tissue to advance the scientific knowledge of PTSD, particularly the identification of PTSD biomarkers. The consortium is directed Dr. Matthew Friedman, who is the founder, former Executive Director, and current Senior Advisor to the National Center for PTSD in White River Junction, VT. In addition to Friedman, members of the brain bank’s Executive Committee include Ann McKee, MD, Neil W. Kowall, MD, and Christopher "Kit" Brady, PhD (Boston VA); Robert J. Ursano, MD and David M. Benedek, MD (USUHS); Ronald S. Duman, PhD (West Haven VA); and Douglas E. Williamson, PhD and Keith Young, PhD (San Antonio VA). Participating sites are located at VA medical centers in Boston, MA (Primary Receiving Site), San Antonio, TX (Secondary Receiving Site), West Haven, CT (Primary Research Site), and White River Junction, VT (Headquarters) along with the Uniformed Services University of Health Sciences at Bethesda, MD (Primary Assessment Site).
The national brain bank has a protocol for post-mortem diagnostic validation and has used this to acquired PTSD brain tissue from existing collections. The consortium will build on this foundation by following the health of enrolled participants during their lifetime through mailed surveys, telephone calls, and electronic health records. Participants in the brain bank will donate their brain and other body tissue after their death. The donated tissue, along with voluntarily participating veteran's health information, will provide crucial information about the biological basis of risk and protective factors in PTSD and related disorders.
For articles, videos, and additional information click here.
Army STARRS was an unprecedented multi-study project headed by the Center for the Study of Traumatic Stress in collaboration with leading academic institutions. Army STARRS was the largest research project of mental health risk and resilience ever conducted among Army personnel.
The project was designed and conducted by an interdisciplinary research team under the leadership of Co-Principal Investigators Robert J. Ursano, M.D. at the Uniformed Services University (Director of CSTS), and Murray B. Stein, M.D., M.P.H., at the University of California, San Diego. The other two major team players were site investigators Steven G. Heeringa, Ph.D., at University of Michigan, and Ronald C. Kessler, Ph.D., at Harvard Medical School. The team included Lisa J. Colpe, Ph.D., M.P.H. and Michael Schoenbaum, Ph.D., collaborating scientists at NIMH, and COL Steven Cersovsky, MD, MPH and Kenneth Cox, MD, MPH, consultants from the U.S. Army Public Health Command.
Army STARRS was a 6-year (2009-2015), 65 million dollar project funded by the U.S. Army with supplemental funding from the National Institute of Mental Health. It consisted of seven separate but integrated epidemiologic and neurobiologic studies designed to comprehensively investigate risk factors and protective factors for suicide, suicide-related behavior and other mental health issues in Army Soldiers. It emphasized the development of practical, actionable information to guide the development and refinement of suicide risk reduction efforts in and beyond the Army.
The research team created enormous databases containing more than 1.1 billion historical administrative Army/DoD records for all the Soldiers (more than 1.6 million Soldiers) on active duty from 2004 to 2009, as well as data collected directly from more than 100,000 active duty Soldiers including Regular Army, activated Army National Guard and activated Army Reserve Soldiers. The team administered more than 177,000 questionnaires, conducted roughly 400,000 neurocognitive tests, and collected approximately 77,000 tubes of blood from approximately 52,000 Soldiers for genetic and other biomarker assays.
The Scientific Advisory Board that was assembled to advise Army STARRS characterized the importance of the project:
Kerry Ressler, M.D., Ph.D., the Chair of the Army STARRS Scientific Advisory Board said: "The breadth and scope of the Army STARRS project is unique in the history of psychiatric and military research..."
LTG (Ret) Eric Schoomaker, M.D., Ph.D., who served on the Army STARRS Scientific Advisory Board, and is a former U.S. Army Surgeon General, said: "The comprehensive nature of these inquiries has provided a data base on behavioral health, social, biological, and potentially genetic pre-determinants of suicide unprecedented in its scope and depth of understanding ..."
As findings became available, the research team reported them to the Army on a regular basis through more than a dozen in-person briefings to senior Army leadership including the Secretary of the Army, the Chief of Staff of the Army, the Vice Chief of Staff of the Army, the Deputy Undersecretary of the Army, the Army Surgeon General, and other senior officials. In this way, the Army could apply the findings to its ongoing health promotion, risk reduction, and suicide prevention efforts.
In December 2013, the research team published a series of four methodological articles in the International Journal of Methods in Psychiatric Research that described the research design and methods to serve as the foundation for other publications that present findings. The first findings from Army STARRS were reported in a series of three articles published in JAMA Psychiatry in May 2014. As of the end of 2018, the team had published a total of 75 papers in scientific journals. The team continues to analyze the rich databases created during Army STARRS, and continues to produce and publish epidemiologic and neurobiologic findings from the multiple Army STARRS studies.
For a summary of published findings please click here.
Due to the great success of Army STARRS, the Center for the Study of Traumatic Stress received funding from the Department of Defense to continue and further develop the STARRS research. Under STARRS-LS, the research team is continuing to use the data systems and research platforms developed during the initial project period to provide further analyses and follow-up studies of the Soldiers who participated in Army STARRS. This work aims to produce additional benefits to the well-being of Service members.
This five-year (2015-2020), $30 million award is to continue analyses of Army STARRS data and expand the research by extending the historical data through 2016 and by conducting a longitudinal follow-up study of more than 50,000 Service members who participated in Army STARRS. STARRS-LS is being designed and conducted by a team of researchers from USU, the University of California, San Diego (UCSD), Harvard and University of Michigan under the leadership of the two co-principal investigators, Dr. Robert J. Ursano of USU (Director of CSTS) and Dr. Murray B. Stein of UCSD.
For more information, visit the STARRS-LS website at starrs-ls.org
Understanding and Meeting the Needs of Children Following Family Member Death
This study, funded by Sesame Workshop, was the Center for the Study of Traumatic Stress Child and Family Program’s preliminary research initiative into the area of family bereavement. It studied the impact of a multimedia program produced by Sesame Workshop in families with young children affected by family member death. The study also addressed the impact of parental death on children and their caretakers in both military and civilian populations by evaluating the helpfulness of a Sesame Workshop DVD and supplemental materials designed for grieving families. The study collected data on the health and well-being of surviving children (ages 2–18. These children lost a parent after September 11, 2001 and the data were observations from their current caretaker.
In order to determine how combat injury affects family members and their children, three studies were conducted. Families participated in (1) a study conducted at the National Military Family Association Operation Purple Healing Adventures Camps, (2) a longitudinal study comparing combat injured and non-injured families from Walter Reed National Military Medical Center, San Antonio Military Medical Center and Fort Stewart, GA, and (3) FOCUS-CI, a pilot randomized-controlled trial that tested the effectiveness of a newly-developed family-centered, strength-based intervention to be used with severely combat-injured service members and their families. Data collected from these three sources will inform programmatic intervention that can better address the needs of service members and their families.
This study examines the impact of severe combat injury on military families through interviews conducted at Operation Purple Healing Adventures (OPHA), an annual summer camp program for combat injured service members and their families sponsored by The National Military Family Association (NMFA). Forty families were assessed in summers 2009 and 2010. Qualitative data is being collected from focus groups to assess the issues related to combat injury and family functioning. Among the issues to be studied is how combat injury effects family life.
The goal of this Child Neglect study is to describe the characteristics of substantiated child neglect cases in the Army, and to identify factors within the family, the military community and the civilian community that contribute either to family health or child maltreatment.. Data were collected from 1,088 questionnaires representing 26 Army installations in the United States, and 400 records of substantiated child neglect cases around the country. Analyses of these data defined the varying types, subtypes and severity of neglect occurring within families, highlighting the importance of varied public health strategies to minimize risk.
Troop Education for Army Morale is an innovative early intervention designed to examine and facilitate post deployment readjustment in U.S. Army Mortuary Affairs Soldiers and their spouses. TEAM is one of the few intervention studies in the history of the Center and also one of the longest ongoing studies at the Center — recruitment began in 2009 and concluded in 2014. A total of 126 soldiers were recruited in 10 cohorts. Participants were randomized either into an educational intervention or a no-intervention comparison group. The intervention is based on the five evidence informed principles of Psychological First Aid: safety (physical and psychological), calming, connectedness, self-efficacy, and hope/optimism. These concepts were delivered through four interactive group workshops, informational handouts, a dedicated website, and supported through concierge phone and email services. Ongoing data analysis includes examination of the impact of TEAM on symptoms of PTSD and depression and quality of life. Results have been presented at several professional meetings, including: the International Society for Traumatic Stress Studies Annual Meeting and the Association of Behavioral and Cognitive Therapies Annual Meeting. Several manuscripts are currently in process. Findings from TEAM will inform future interventions with military and civilian populations.
U.S. Army mortuary affairs (MA) soldiers recover, identify, and evacuate the remains of the deceased from the theater of war. This study examines the individual, unit and family stressors, risk factors and resiliency of MA soldiers returning from deployment to the Middle East compared to MA soldiers anticipating deployment and those not deployed. Survey are administered to MA units approximately one month prior to and one month after return from deployment to the Middle East. The surveys assess MA soldiers’ exposures during deployment as well as pre and post deployment mental health and well-being. This study has implications for early intervention, training, education, leadership and health surveillance. Findings will target resiliency, preparation, training and education of troops for the stressors of deployment and working with the dead.
The Daily Diary Study uses a novel ecological momentary assessment methodology to monitor post-traumatic stress symptoms in current and former Service members. The study examines the association between variability in stress symptoms, collected four times daily over a 15-day period, and psychiatric disorders (e.g., PTSD, depression), sleep, pain, health risk behaviors (e.g., alcohol and tobacco use), and other areas of health and functioning. In Phase I of the study, Service members complete daily assessments on paper questionnaires. Recruitment for Phase I began in 2013 and closed with enrollment of 50 Service members. Recruitment for Phase II began in 2014 and is ongoing. In Phase II, Service members complete assessments using electronic tablets programmed with a sophisticated application developed specifically for this project through the collaboration of CSTS and the National Center for Telehealth and Technology (T2). Data analyses and dissemination of the findings is in process. This important study will increase our understanding of the relationship between daily variability in post-traumatic stress symptoms and mental health conditions, as well as inform future use of technology in psychiatric assessment, treatment, and research.
This study aims to identify experiences of bereaved military family members (adults and children) — how psychological and/or physical outcomes of bereavement are influenced by family members’ pre-existing psychological and physical health, genetic factors, support and unique factors associated with military death. Expert consultants from Columbia University, UCLA, and University of Michigan are also collaborating on study analyses.
Grief is a normal process that usually improves over time. The National Military Family Bereavement Study (NMFBS) conducted by the Uniformed Services University has determined that a sizeable portion of bereaved military family members suffer prolonged levels of grief and distress. This prolonged distress puts them at risk for harmful long-term changes in physical and mental health. Recognizing the need to help bereaved military families and friends, the NMFBS formed a partnership with the Center for Complicated Grief at Columbia University to create a program for bereaved military families and friends to better manage grief, guilt, and anger. The program, entitled GRIEF STEPS, is an app-based/Internet program designed to lower grief and decrease risk for long-term problems. GRIEF STEPS will be tested in a “randomized controlled trial,” which means that we will ask bereaved military family members and close friends to participate and then assign them to one of two groups, either the GRIEF STEPS group or a “control” group that will focus on building resilience. The study will compare how the people in each group do in overall improvement in grief severity and adaptation to loss. Both groups will have guides who can help or answer questions about the intervention. If GRIEF STEPS is successful, it would be a helpful resource for current and future survivors who suffer the death of a military loved one.
The Center for Study of Traumatic Stress and VOICES of September 11 partnered to examine long-term positive and negative bereavement outcomes (including grief, traumatic symptoms, resilience characteristics and post-traumatic growth) following a terrorism-related death. Participants were family members bereaved by the bombing of Air India Flight 182 on June 23, 1985 or by the events of September 11, 2001. Participants completed an online questionnaire about their experiences related to the aftermath of these events and the death of their family member(s). The questionnaire assessed the following: background factors; characteristics of the death; availability of post-death resources; media involvement; memorialization; psychological functioning; and life changes. This information will be used to develop preliminary working models for understanding risk and protective factors for bereaved family members of terrorism-related deaths. These results will inform ongoing research and guide training and counsel for disaster and terrorism victims and their families.
Currently, recommended medications for combat-related posttraumatic stress disorder (PTSD), which increase the availability of serotonin (SSRIs) or serotonin and norepinephrine (SNRIs) in the brain, do not adequately relieve symptoms for many patients. There is therefore an urgent need to investigate other types of medications that may be more effective. Riluzole is a medication that reduces glutamate activity in—and may help reverse damage to—areas of the brain (amygdala, anterior cingulate cortex, and hippocampus) where an excess of glutamate is believed to contribute to PTSD symptoms. The Center for the Study of Traumatic Stress has a study now underway at Walter Reed National Military Medical Center and Syracuse VA Medical Center that is evaluating the efficacy of riluzole in 100 Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans with combat-related PTSD with current ineffective SSRI or SNRI treatment. This is a randomized controlled, double-blind trial; half the participants receive riluzole, and half receive a placebo for 8 weeks. PTSD, depression, and anxiety symptoms are assessed once a week, and magnetic resonance spectroscopy (1H MRS) is being done pre- and post-treatment. It is hypothesized that (1) participants who receive riluzole will have better PTSD symptom improvement than those who receive placebo; (2) participants who receive riluzole will have more improvement in depression and anxiety symptoms and overall functioning compared to those who receive placebo; and (3) pre- to post-treatment changes in amygdala, anterior cingulate cortex, and hippocampus, measured using 1H MRS, will be consistent with treatment with riluzole versus placebo.
PTSD is a prevalent, disabling, and costly condition, and the current need for effective PTSD treatments is great. Several effective psychotherapies(prolonged exposure; cognitive processing therapy) for PTSD are already widely used, but many patients with PTSD either do not have access to quality psychotherapy or may prefer treatment that is less time-consuming and emotionally intensive. Current pharmacologic therapies such as selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) provide substantial benefit to only 30-40% of patients, and often produce side effects that limit adherence. Therefore, there is a need to investigate other types of medications to offer more effective options to patients with PTSD. The renin-angiotensin system is a biochemical pathway essential for cardiovascular regulation, and targeting this pathway using angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE-I) inhibitors has been an effective treatment for hypertension for many years. Increasing evidence supports the role of the renin-angiotensin pathway in stress-related psychiatric disorders independent of its cardiovascular effects. Losartan is an ARB commonly used to treat high blood pressure that showed potential in preclinical studies to reduce PTSD symptoms by reducing fear memory and regulating the stress response. The Center for the Study of Traumatic Stress, under a subaward from the University of California San Diego is conducting a clinical trial at Walter Reed National Military Medical Center and George Washington University testing the efficacy of losartan in individuals with a diagnosis of PTSD. This randomized controlled double-blind trial tests losartan against placebo for 10 weeks. Study hypotheses include: (1) participants who receive losartan will have greater PTSD symptom improvement than those who receive placebo; and (2) participants receiving losartan with a specific variant of the angiotensin converting enzyme gene (rs4311 - CC genotype) will show better PTSD symptom improvement with losartan treatment than participants with other variants.
LTC Gary H. Wynn, MD, senior center scientist, is leading an effort to better understand the relationship between PTSD and sleep disorders in the military. Sleep disorders are a frequent problem among service members and even more so among those suffering with PTSD. This effort will seek to understand the relationship between these entities and to optimize treatment selection for military healthcare system clinicians seeing patients with these conditions. The effort, in collaboration with Harvard Medical School, will use existing datasets and state-of-the art analytic methods to dive in to this question. The study will use heterogeneity of treatment effects (HTE) analyses to identify predictors of variation in sleep disturbance treatment response and develop predictive analytic models to improve treatment selection for individuals with PTSD-related and other sleep disturbances.
The Center, in collaboration with the University of California, Irvine (UCI), established a multi-species methodology for evaluating potential new compounds to treat PTSD. The effort, led by senior center scientist LTC Gary H. Wynn, MD, uses a non-mammalian model (zebrafish) for high-throughput rapid screening in conjunction with a long established rodent model. The zebrafish colony, a new species for the USUHS community, will provide an abundance of potential research opportunities in drug development and beyond.
The zebrafish lab has recently begun initial tests of various chemical panels for standardization of profiles within the zebrafish model. In addition to high throughput embryo testing the lab has begun ramping up efforts to perform testing in adult zebrafish which have over 100 testable characterized behaviors. Once fully established the lab will begin high throughput testing and coordinate with its collaborators regarding future directions for compound screening. Several novel compounds are pending testing currently and successful compounds will then be evaluated in the established rodent model at UCI.