PTSD Biomarkers Discovered in the Blood of Soldiers

Post-traumatic stress disorder (PTSD) is a type of anxiety disorder that occurs after experiencing or witnessing a stressful, frightening or distressing event. Military personnel are at a higher risk of developing PTSD based on distressing experiences while serving and combat exposure. Depending on the type of service, PTSD is estimated to affect approximately 11–30% of veterans.

The hallmark symptoms of PTSD, including flashbacks, memory issues, avoidance behaviors and intrusive thoughts, are symptoms shared with other anxiety disorders, making its diagnosis challenging. “Improved methods of screening and predicting PTSD could inform better treatment approaches by providing a deeper understanding of the underlying biological mechanisms of the disorder,” says Stacy-Ann Miller, a scientist at the Walter Reed Army Institute of Research (WRAIR).  

Can molecular approaches offer a helping hand? At the annual meeting of the American Society for Biochemistry and Molecular Biology, Miller presented new unpublished research that suggests people experiencing PTSD present with biomarker patterns in a simple blood test.

Biomarkers are a broad category of biological molecules that reflect the biological processes occurring within a cell, tissue or the entire body. Increasingly, biomarkers are being discovered, validated and tested for use as diagnostic tools, where the presence, absence or quantity of a molecule can be used to determine a person’s health status. The new research centers around the potential of using blood-based biomarkers for improving the accuracy of PTSD diagnosis and tailoring treatments for specific subtypes.

Study recruits over 1,000 service members

The longitudinal study presented by Miller is a large, group effort from the PTSD Systems Biology Consortium, a network of government and academic laboratories. “The goals of the PTSD Systems Biology Consortium include developing a reproducible panel of blood-based biomarkers with good sensitivity and specificity for PTSD diagnosis and is made up of more than 45 researchers,” Dr. Marti Jett, civilian senior executive for S/T, Systems Biology at the U.S. Army Medical Research & Development Command/WRAIR, one of the consortium’s three team leaders, explains to Technology Networks.

The researchers recruited nearly 1,800 service members, making the work the largest prospective study to assess the biological markers of PTSD over time that has been conducted to date. “The participants were active-duty Army personnel of the 101st Airborne at Fort Campbell, Kentucky. They were assessed before and after being deployed to Afghanistan in February 2014 (index deployment) and are referred to as the Fort Campbell Cohort (FCC),” explains Miller. The study sample ranged in age from 25–45 years-old, and approximately 6% of participants were female.

The male participants were divided into subgroups based on measures of PTSD and mental resilience, including:

• PTSD subgroup (146 participants)
• PTSD sub-threshold (171 participants)
• High resilience group (502 participants)
• Low resilience group (505 participants).
  
  

Resilience was classified based on a number of different measures including PTSD, anxiety, sleep quality, alcohol use disorders, combat exposures, traumatic brain injury and general physical and mental health. The participants submitted blood samples which were collected before, 3 days after a 10 month-deployment and 90–180 days post-deployment. The researchers analyzed the levels of four biomarkers in the blood previously linked to stress, depression, anxiety and mental health disorders, including:

• The glycolytic ratio – a measure of how the body breaks down sugar to produce energy
  
• Arginine – an amino acid, which is important for immune and cardiovascular system functions
  
• Serotonin – a neurotransmitter often dubbed “the happy hormone”, which supports sleep regulation among other functions
• Glutamate – a neurotransmitter central to learning and memory.

When comparing the biomarkers across the cohort, the team found that individuals with PTSD or sub-threshold PTSD had a significantly higher glycolytic ratio, and reduced levels of arginine compared with individuals categorized as highly resilient. “The PTSD group also has lower serotonin and higher glutamate than the high resilience group, which is clinically correlated to depressive and anxiety symptoms in the PTSD group,” the authors share in the abstract. “These metabolic differences were not explained by gender, age, body mass index, smoking, or consumption of energy drinks/coffee.”

Technology Networks asks Miller whether the biomarkers analyzed are specific to PTSD, or whether they could be indicative of other anxiety disorders. “We are not able to link the biomarkers we measured to specifically PTSD only. The current direction of our study is to develop a screening tool for early identification of signatures related to features of PTSD,” she says. However, the blood-based markers – which included metabolites, epigenomic, immune, inflammatory and liver function markers – complemented the most important predictors of PTSD, Miller emphasizes.

She adds, “Many of the early aspects of PTSD are sleep disorders, circadian rhythm disruption, uncontrolled anger, somatization, a tendency for substance abuse and other self-destructive actions. These aspects of PTSD contribute to the disruption of family, work and social networks. An objective screening tool, applied early, is aimed to get vulnerable persons into [an] appropriate treatment program and avert those disruptions and legal issues related to substance abuse.”

“Emerging data suggests that this condition is a multisystem disorder affecting many biological systems including cardiovascular, liver metabolism and the immune system, raising the possibility that peripheral markers of illness may have utility in establishing the diagnosis of PTSD. At the current time, there are no validated biomarkers or laboratory tests that distinguish among trauma survivors with and without PTSD,” says Miller.

The complexities of biomarker discovery and validation

Biomarker discovery and validation is a rigorous and complex process. The research team emphasize that further research is required to confirm the biomarkers’ potential use in real-world settings. However, they are optimistic: “This abstract deals with one of the three panels we have developed as a means to address PTSD in Military service members,” Jett describes. “The goal is to use these findings to be able to focus on subtypes of PTSD in order to provide targeted treatment and to enable development of additional treatment regimens.” This information carries potential for enabling clinical treatments that can focus on specific types of PTSD, which may respond differently to various types of therapy. “Cancer research has demonstrated that focusing on subtypes that respond to a particular therapy enables design of a targeted approach,” adds Jett. As for next steps, Miller states that the team would like to develop a US Food and Drug Administration-approved panel.

“In addition, previous studies have identified several promising biomarkers of PTSD, however like many things in research this was in mainly combat-exposed males,” she says.

Now, more women are now serving on the front line, and research must be representative of the entire military personnel. “According to the Veterans Administration, female soldiers are more than twice as likely to develop PTSD as males (10% for women and 4% for men). We would be interested in identifying gender-specific biomarkers that will improve clinical assessment for female soldiers,” says Miller.

The team would also like to apply their research to the civilian population that experiences PTSD. “The research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Miller concludes.

This article is based on research findings that are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.

Dr. Marti Jett and Stacy-Ann Miller were speaking to Molly Campbell, Senior Science Writer for Technology Networks.