Soldiers and police officers show elevated rates of post-traumatic stress disorder (PTSD) due to repeated exposure to disturbing or distressing experiences. NYU Langone researchers are using advanced computational techniques to identify multiple, interacting factors that place some individuals at higher risk—findings that could someday be used to design preventive interventions.

A Combination of Biomarkers Indicate Heightened Risk for Soldiers

In 2020, NYU Langone–led teams published two studies that harnessed this approach to analyze the effects of an unprecedented range of variables. The first paper, which appeared in June in the journal Molecular Psychiatry, analyzed results from the Fort Campbell Cohort Study, a prospective longitudinal study that examined the value of using a large, multidimensional dataset collected from soldiers before deployment to Afghanistan to predict post-deployment PTSD status. This dataset consisted of polygenic, epigenetic, metabolomic, endocrine, inflammatory, and routine clinical lab markers as well as computerized neurocognitive testing and symptom self-reports.

The analysis was computed using data from 473 active-duty Army personnel of the 101st Airborne Division at Fort Campbell, Kentucky. Approximately half were first-time deployed; the remainder had been deployed either once or twice before. The soldiers were assessed three times: just before deployment in February 2014, 3 days after returning from a 10-month tour of duty, and 90 to 180 days after deployment.

On the basis of prior studies in humans and animals, the researchers amassed a list of 105 potential risk factors associated with PTSD. They then used machine learning to analyze how strongly these candidate predictors correlated with a post-deployment diagnosis in the Fort Campbell cohort. Among the highest-ranked predictive factors, the team found, were pre-deployment sleep quality, anxiety, depression, sustained attention, and cognitive flexibility. Blood-based biomarkers including metabolites, epigenomic, immune, inflammatory, and liver function markers complemented the most important neurocognitive predictors.

“This is one of the first-ever studies of a well-characterized, highly combat-exposed group of military personnel,” notes senior author Charles R. Marmar, MD, the Lucius N. Littauer Professor of Psychiatry, chair of the Department of Psychiatry, and director of the Cohen Veterans Center at NYU Langone. Dr. Marmar is also a principal investigator for the PTSD Systems Biology Consortium—the multi-institution research group, funded by the Department of Defense, under whose auspices the Fort Campbell Study was conducted. “Eventually, findings like these will help us stratify the risk of PTSD for individual fighters before they enter combat. They’ll enable us to make a diagnosis of PTSD objective rather than subjective. And they’ll help guide treatment selection, enabling us to predict which therapies will be most effective for which soldier.”

Finding the Likeliest Causes of Post-Traumatic Stress in Police Officers

In August, researchers led by Glenn Saxe, MD, professor of in the Department of Child and Adolescent Psychiatry at NYU Langone, published in the journal Translational Psychiatry, the first study attempting to identify the leading causes of post-traumatic stress (PTS) in police officers. The scientists showed that a combination of genetic and emotional differences lead some officers to develop PTS after experiencing trauma, while others do not.

The team analyzed data collected on 207 police officers from departments in New York City, San Francisco, and San Jose who were diagnosed with PTS. All had experienced at least one life-threatening event during their first year on the force. Using a variety of advanced techniques—including machine learning and an analytical model known as computational causal discovery (CCD)—investigators at NYU Langone and the University of Minnesota searched for patterns in 148 characteristics that previous research had found to be associated with PTS.

After identifying 83 pathways that could have led officers in the cohort to develop the condition, the researchers pinpointed the factors that appeared most frequently. Each pathway, they found, shared one of five causes. Three were neurobehavioral: a tendency to startle at sudden sounds, severe distress following a traumatic experience, and early-career displays of mental health symptoms such as anxiety or depression. Two of the causes were genetic: mutations in the histidine decarboxylase (HDC) gene, which is linked to immune system problems, and mutations in the mineralocorticoid receptor (MR) gene, which is involved in the body’s fight-or-flight response to threats.

Directions for Future Research—and New Therapies

“Several of the causal factors we identified—the startle response, the HDC gene, and the MR gene—point to well-mapped neural circuits, which could be targeted with drugs or behavioral therapies,” Dr. Saxe notes. Other interventions, he adds, might target factors that can lead indirectly to PTS but fall outside the top causes identified by this study. One example is difficulty adjusting to work, which contributed to PTS development in 60 percent of patients. Addressing such factors (for example, through counseling) might reduce officers’ risk.

Although further research will be needed to confirm these findings, their therapeutic value could prove to be far-reaching. “Once we learn the causes of PTS, we can treat people before they have the chance to develop full-blown PTSD,” says Dr. Marmar. “We could also use that knowledge to improve quality of life for police officers and other emergency responders by helping them cope more effectively with work-related stressors.”

Such research may have implications for broader populations as well. In the future, Dr. Saxe and his colleagues plan to apply similar computational techniques in a larger group of traumatized adults and children, examining a more extensive set of factors.