6 June 2020

Omics Characterization of Combat-Related PTSD: Early Onset and Female Studies

Throughout the military’s history, people have recognized that exposure to traumatic warzone events is often associated with post-traumatic stress disorder (PTSD). The illness is marked by clear symptoms such as intrusive memories, avoidance, negative changes in thinking and mood, and changes in physical and emotional reactions, yet understanding the etiology of the illness remains elusive.

According to the National Center for PTSD, the number of veterans with PTSD in a given year varies by service era:

• Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF): 11%-20% of veterans
• Gulf War (Desert Storm): 12% of Golf War veterans
• Vietnam War: An estimated 30% of Vietnam veterans

 

A Geneva-managed research study titled, “Omics Characterization of Combat-Related PTSD: Early Onset and Female Studies” is led by Geneva Principal Investigator Dr. James Meyerhoff along with Dr. Rasha Hammamieh at Walter Reed Army Institute of Research (WRAIR) North. The research team aims to better predict early signs of the comorbidities inherent in PTSD (anger management, sleep disorders, etc.) so that readily available treatments can be implemented to avoid the downward spiral to full PTSD. In the work with Soldiers from Fort Campbell, at ~ 3 months post-return from deployment, ~20% showed some of these co-morbidities; classic interventions at that point could improve soldier readiness and resilience, but most importantly, aid them to avert full PTSD. This research is sponsored by the Army Research Office (ARO), U.S. Army Combat Capabilities Development Command’s Army Research Laboratory (ARL) under a cooperative research and development agreement, or CRADA.

Systems biology approach

The research program applies a systems biology approach to improve data analytics to further understand the causes of PTSD and provide markers of PTSD for more accurate and earlier diagnosis.

The approach can simulate aspects of PTSD in humans and model organisms to discover and evaluate objective biomarkers. It is a strategy where many types of data across different biological systems are integrated using the SysBioCube, a data warehouse and integrative data analysis platform developed by the Army for DoD researchers housed at NIH, which combines all of the data into one single place to perform a multi-omic analysis (a new approach where the data sets of different omic groups such as genome, proteome, transcriptome, epigenome, and microbiome) are combined during analysis. The SysBioCube allows research teams and members of the PTSD Systems Biology Consortium nationwide to share, analyze and harmonize data sets.

Recent work

In a recent manuscript published 2 June 2020 in Molecular Psychiatry, the research team found the highest-ranked predictive features collected from a cohort at Fort Campbell before they deployed to Afghanistan were: pre-deployment sleep quality, anxiety, depression, sustained attention, and cognitive flexibility. They also identified blood-based biomarkers that complemented the most important predictors.  (Schultebraucks K, published online ahead of print, 2 Jun 2020). These issues could be addressed prior to deployment, with the aim of averting full PTSD.

“The PTSD Systems Biology Consortium identified stable molecular signatures (Dean, et al) for objectively screening for PTSD in military personnel,” said Dr. Marti Jett, chief scientist, systems biology at U.S. Army Medical Research & Development Command, WRAIR. “The screening tool aims to pinpoint molecular features of PTSD inherent co-morbidities such as sleep, anger, hyperarousal, etc. so that targeted treatments, available on most military bases, can be used early in the illness to avert the label, PTSD and maintain soldier readiness for the next deployment.”

Females in the military with PTSD

Previous studies from the same team (Dean et al) have identified several promising biomarkers of PTSD in combat-exposed males. Researchers also aim to identify gender-specific biomarkers that will improve clinical assessment for female soldiers. The research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions.

With more women serving on the front lines, the military faces new challenges in how combat affects the female psyche. The study builds upon those earlier results and aims to identify predictors to improve early detection and expand findings to identify gender-specificity and determine how changes in the brain, blood, and major organs characterize the illness.

Female soldiers are more twice as likely to develop PTSD as males (10% for women and 4% for men), says the Veterans Administration. While both men and women report the same symptoms of PTSD, some can be more common for women or men. Other environmental and traumatic factors can also play a major role in triggering PTSD. Further research is needed to fully understand the effects of women’s exposure to PTSD.

Informing relevant prevention efforts for soldiers pre-deployment could help predict biological outcomes, highlighting the importance of reducing PTSD severity with early intervention.

Fortunately, there are treatment options for PTSD. For veterans and caregivers, the National Center for PTSD provides treatment options and resources on coping with the residual effects of war.

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To connect with Geneva’s Brain Health program experts, please contact us.

Works Cited

Schultebraucks K, Q. M.-A. (published online ahead of print, 2 Jun 2020). Pre-deployment risk factors for PTSD in active-duty personnel deployed to Afghanistan: a machine-learning approach for analyzing multivariate predictors. Mol Psychiatry, 2020; 10.1038/s41380-020-0789-2. doi: 10.1038/s41380-020-0789-2.  Published online 2018 Sep 5. doi: 10.1159/000491431

Dean, K.R. et al. Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder. Mol Psychiatry (2019). https://doi.org/10.1038/s41380-019-0496-z

Ruoting Yang, et al  A DNA methylation clock associated with age-related illnesses and mortality is accelerated in men with combat PTSD. Mol Psychiatry (2020). https://doi.org/10.1038/s41380-020-0755-z