By carefully tracking 5,000 people after they have experienced a traumatic event, a just-launched NIMH-funded study aims to provide a finely detailed map of the array of factors that play a role in the development of mental disorders that occur in the wake of trauma. Information coming out of the study should provide a much deeper understanding of the mechanisms that give rise to post-traumatic disorders as well as a clearer basis for predicting who will be affected and how best to target treatment.
Following a traumatic event—be it an assault, a car crash, or a combat experience—it is common for people to report a range of symptoms, including hypervigilance, intrusive upsetting thoughts, flashbacks, and changes in sleep and mood. These often co-occur with chronic pain and substance use, as well as other enduring effects from body or brain injuries. Most individuals gradually get better, but a substantial number develop persistent problems, often diagnosed as post-traumatic stress disorder (PTSD). There is no reliable way to predict who will recover without treatment and who will develop lasting problems after trauma.
Even when PTSD or other disorders such as anxiety and depression are diagnosed, symptoms differ person to person, as does response to treatment.
Researchers at the University of North Carolina (UNC) School of Medicine at Chapel Hill and Harvard University will collaborate in the multicenter Aurora study, initially screening 5,000 people arriving in emergency rooms after trauma. After an initial evaluation and a baseline collection of biological data from blood samples, participants will be monitored for the next several months in a variety of ways, including through the use of mobile technology, such as wrist wearables and smart phones, to track factors like activity, sleep, and mood. In-depth exams will include additional blood samples, functional (non-invasive) brain imaging, and psychological tests. Participant involvement will continue over a year, generating a wide variety of detailed information on, for example, health history (including that of earlier trauma), genetics, stress responses (physical and psychological), behavior, and cognition. The data will be de-identified to protect patient privacy.
Samuel McLean, M.D., M.P.H., at UNC will lead the study in collaboration with Ronald Kessler, Ph.D., at Harvard Medical School, Karestan Koenen, Ph.D., at the Harvard School of Public Health, and Kerry Ressler, M.D., Ph.D., at McLean Hospital, Belmont, MA. These investigators bring the varied expertise necessary for this multi-dimensional study, which will involve screening and recruitment of patients; collecting and storing the wide variety of data and biological samples being collected; analyzing the large volume of data, including genetic findings; and using that data to provide a deeper understanding of the origins of post-traumatic illness. The study has been designed to ensure that data and biological samples can be shared with the field, making possible further analyses by other investigators. Biological samples, for example, will be stored under the NIMH Human Genetics Intitiative , while data will be accessible through the NIMH Data Archive.
The variety and level of detailed information sought in this study reflect NIMH’s encouragement of neuroscientists to orient investigations towards the Research Domain Criteria (RDoC) framework—a research framework being developed based on the diverse information coming out of genetics, neuroscience, and behavioral studies. RDoC aims to provide a framework for linking specific symptoms to their complex underlying causes—likely to differ person to person. Such a framework represents an alternative to the use in research of more traditional diagnostic categories based on collections of symptoms. The RDoC approach is a step towards diagnosis and treatment targeted to the individual, aiming toward the goal of precision medicine.
In 2012, the White House issued an executive order calling for investments in research that address PTSD, traumatic brain injuries, and suicide prevention. Consistent with the aims of the 2013 National Research Action Plan (called for in the executive order), this study has the potential to identify underlying causes of impairment and new targets for interventions that will improve the care of individuals at high risk for post-traumatic stress conditions across civilian, military, and veteran populations.
“Trauma-related disorders affect millions of Americans and are a central concern for the health and security of the nation,” said Farris Tuma, Sc.D., chief of NIMH’s Traumatic Stress Research Program. “Because of the lack of understanding of what contributes to these disorders, predicting outcomes for individuals—and treating them effectively—remain major scientific and public health challenges. While treatments are effective for many patients, not all benefit equally, and we lack effective prevention strategies. We are frustrated but not surprised that people respond differently to the best available treatments and must learn how to tailor existing and new interventions to specific patient needs.”
NIMH is providing $21 million in funding over five years for the study.
“This study reflects the need for our research investments to address short- and medium-term clinical goals, as well as long-term basic research,” said NIMH Director Joshua A. Gordon, M.D., Ph.D. “In the relatively short term, this project is expected to deliver tools for clinicians to make informed decisions about risk and follow-up care soon after trauma. In addition, the research resource to be created will fuel a new generation of analyses on the underlying causes of disorders, identify new intervention targets, and in turn give rise to mechanism-informed treatments based on individual needs.”