New research suggests that a simple blood sample taken in the emergency room may enable doctors to predict if a recent trauma victim is likely to develop chronic post-traumatic stress disorder (PTSD) within a year. Such a predictive test, if perfected, would enable treatment to begin at once in the most vulnerable patients, possibly diminishing or even preventing PTSD or other adverse consequences.

In the newly reported study, published in the American Journal of Psychiatry, a team that included five BBRF grantees found that in a sample of patients being treated for trauma in a hospital emergency department, those whose blood had low levels of two pro-inflammatory molecules, called TNFα (tumor necrosis factor-alpha) and IFNγ (interferon-gamma), were at significantly greater risk of developing chronic symptoms of PTSD within a year—compared with trauma patients who did not have low levels of these molecules.

A key point in the research is that predictions were made based on analysis of blood drawn in the immediate aftermath—within a few hours—of patients’ exposure to trauma. Many of the body’s systems respond to trauma, including stress hormones and cells of the immune system. These responses have characteristic patterns; every component does not respond at once, or on the same schedule. Complicating the matter is the fact that elements of the immune and endocrine systems can have both helpful and harmful impacts, depending on the biological context.

Past research has shown that people who have high “baseline” blood concentrations of several pro-inflammatory molecules tend to be at greater risk of developing PTSD if they happen to be exposed to trauma. The new study asked a pragmatic question: if an emergency room physician did not know a new trauma patient’s baseline levels of pro- and anti-inflammatory factors, would it nevertheless be possible to predict the patient’s risk of PTSD?

The team performed a complex analysis of blood samples drawn within 3 hours of trauma exposure in 505 patients being treated in the emergency department of an Atlanta hospital over a 4-year period. In addition to contributing blood samples, each patient underwent a 1.5-hour psychiatric interview. Follow-ups were given at 1, 3, 6, and 12 months following trauma exposure, in which 270 of the original patients participated.

Of these 270 patients, 10%, were diagnosed with chronic PTSD at the one-year follow-up (called the “chronic” group); 59% had no PTSD symptoms at that point (called “resilient”), while 31% had experienced some PTSD symptoms but were improving by the one-year marker (“recovery” group).

The results, while clear regarding the correlation of low levels of TNFα and IFNγ immediately post-trauma and the subsequent development of PTSD, did not implicate other pro-inflammatory markers in the blood, indicating that the mechanisms underlying these relationships are still unknown. The study was also unable to determine if the low levels of the two markers in the “chronic” group reflected a pre-existing deficit in these individuals, or perhaps a situation in which trauma blunted the ability of their immune system to respond properly.

What could be said with certainty, however, was that it was possible to measure immune system changes that occur in response to a recent trauma, and that is was possible to assess the pro-inflammatory immune response right after the event, in the emergency department. The research thus suggested the feasibility of routinely detecting predictive markers in the blood indicating patients at greatest risk of developing PTSD or other adverse conditions such as depression after being exposed to trauma.

First author of the study was Vasiliki Michopoulos, Ph.D., of Emory University School of Medicine. Senior members of the team included Charles Nemeroff, M.D., Ph.D., BBRF Scientific Council member, 1997 Selo Prizewinner and 2003 and 1996 BBRF Distinguished Investigator; and Kerry Ressler, M.D., Ph.D., BBRF Scientific Council member, 2009 Freedman Prizewinner, 2017 BBRF Distinguished Investigator and 2005 and 2002 Young Investigator. Also on the team were Barbara Rothbaum, Ph.D., 2012 BBRF Distinguished Investigator; Isaac Galatzer-Levy, Ph.D., 2015 BBRF Young Investigator; and Eleonore Beurel, Ph.D., 2013 and 2008 BBRF Young Investigator.