Genetic and Environmental Predictors of Combat-Related PTSD

Aug 18, 2010

The more you know about your enemy, the better equipped you are to fight. That’s true in war, and it holds true in our battle against physical and mental ailments.

As researchers have learned more about the root causes of heart disease and other physical afflictions, the medical field has responded with a wide array of new prevention, diagnostic, and treatment methods. STRONG STAR hopes to help achieve equally valuable advances in the fight against posttraumatic stress disorder (PTSD) as it strives to understand how we respond to and are affected by trauma at the most basic biological level – our DNA.

What do we know about the causes of PTSD?

Currently, there is not a good understanding of how PTSD develops after exposure to a trauma, particularly combat-related stress, and what factors lead to increased vulnerability or resilience. Although every person with PTSD has been exposed to a traumatic event, research shows that the majority of people who experience a trauma do not develop PTSD. Why is it that some people remain resilient after trauma; some experience difficulties in the short term but heal from their psychological wounds fairly quickly; and others develop a chronic problem with PTSD?

We have some clues. Multiple environmental factors have been shown to affect PTSD risk, including the nature of the trauma itself, how many traumas a person has faced, age at the time of trauma, early life adversity, as well as an individual’s level of social support.

On the other hand, studies with families and twins provide evidence that susceptibility to-or resilience against-PTSD is at least partially inherited. For example, Sack and colleagues published a study in 1995 showing that Cambodian refugee children of parents with PTSD had a 5-fold greater risk than refugee children of parents without PTSD. A twin study published by K.C. Koenen in 2007 concluded that genes account for approximately 30% of the variance in PTSD risk.

As with other complex diseases and mental health disorders, the root causes of PTSD are likely to be varied and intertwined, with contributions by genetics, environmental factors, and the interplay between the two.

How does STRONG STAR plan to get to the root of the problem?

Douglas E. Williamson, PhD, with the University of Texas Health Science Center at San Antonio is working to untangle this complicated web with a study he has developed for STRONG STAR. In the first large-scale prospective study of its kind, Dr. Williamson and his colleagues are looking at changes in the expression of genes as a result of combat-related stress associated with the development of PTSD. The study is enlisting the help of approximately 4,000 Army Soldiers who volunteer to provide blood samples and answer a variety of questions before and after deployment to Afghanistan. Through their study participation, these service members will allow researchers to collect the necessary data and perform the analyses needed to identify genetic risk factors that influence the development of combat-related PTSD.

All study participants will be screened prior to deployment. Then, upon their return to the U.S., those who are identified through routine military screening to have symptoms of PTSD will be invited to participate in a second study assessment. An equal number of those who do not show symptoms of PTSD-matched for combated-related stress, gender, military unit, and rank-likewise will be invited to participate in this second round of assessments.

With the data gathered, Dr. Williamson and his colleagues aim to do three things:

• Determine whether there are changes in gene expression-that is, the activity or output of particular genes-associated with the onset of PTSD after exposure to combat-related stress. In other words, can exposure to combat-related stress affect the way our genes behave, the RNA they make, ultimately resulting in the alteration of the body’s production of various proteins and hormones? Do those changes contribute to the development of PTSD?
• Identify specific variants in the genetic architecture involved in deployment-related changes in gene expression and associated with PTSD. Here researchers want to see which genes are sensitive to combat-related stress and how changes in their expression are linked with the development of PTSD.
• Identify significant interactions between noncombat-related stressors and genes that are linked with the onset of PTSD. For example, were there genetic variations even before deployment in individuals who were exposed to early childhood trauma that potentially increased sensitivity to combat-related stress? Are genetic variations seen in individuals who have been experiencing other ongoing stressful life events? Are there associations with these genetic changes and increased PTSD risk after exposure to combat-related stress or as combat-related stress levels increase?

Answers to these questions will help researchers understand what happens with our genes and related basic biology as we are exposed to trauma. This, in turn, could enlighten new intervention efforts, including medication treatments that offset biological factors that lead to PTSD’s development.

Study participants who exhibit symptoms of PTSD following deployment will be offered the opportunity to enroll in ongoing STRONG STAR treatment trials or referred to other clinical resources that can help them recover now. And thanks to these service members’ study participation, STRONG STAR researchers expect to find ways to improve future PTSD prevention and treatment efforts, with the potential to help countless service members, veterans, and civilians for years to come.