Variations of Stress Response Gene Appear To Be Predictive of Risk of Posttraumatic Stress Disorder Symptoms

Adults who experienced child abuse and have variations of a gene related to stress response appear to be at greater risk of posttraumatic stress disorder symptoms as adults, according to a study in the March 19 issue of JAMA, a theme issue on Genetics and Genomics.

Rebekah G. Bradley, Ph.D., of the Emory University School of Medicine, Atlanta, presented the findings of the study at a JAMA media briefing at the National Press Club in Washington, D.C. 

“Posttraumatic stress disorder (PTSD) is a debilitating stress-related psychiatric disorder, with prevalence rates of at least 7 percent to 8 percent in the U.S. population, and with much higher rates among combat veterans and those living in high-violence areas. Initially viewed as a potentially normative response to traumatic exposure, it became clear that not everyone experiencing trauma develops PTSD. Thus, a central question in research on PTSD is why some individuals are more likely than others to develop the disorder in the face of similar levels of trauma exposure,” the authors write. They add that it is becoming clear that there are critical roles for pre-disposing genetic and environmental influences in determining the psychological risk to the traumatized individual, with child abuse appearing to provide significant risk for the development of PTSD.

Dr. Bradley and colleagues conducted a study to determine the role of variations (polymorphisms) in one of the genes related to stress response, FKBP5, in predicting PTSD symptoms in a sample of highly traumatized, low-income men and women living in an urban area, and whether these genetic variations interact with increasing levels of both child abuse and other types of trauma exposure to be a predictor of PTSD symptoms during adulthood.

The study consisted of an examination of genetic and psychological risk factors in 900 general medical clinic patients with significant levels of childhood abuse as well as other types of trauma, using a survey combined with genetic testing (single-nucleotide polymorphism [SNP] genotyping). Participants were primarily urban, low-income, black men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital, between 2005 and 2007.

The researchers found that both level of child abuse and level of other types of trauma each separately predicted level of adult PTSD symptomatology. Although genetic variations (FKBP5 SNPs) did not directly predict PTSD symptom outcome or interact with level of non–child abuse trauma to predict PTSD symptom severity, four variations (SNPs) in the FKBP5 locus (the specific site of a particular gene on its chromosome) significantly interacted with the severity of child abuse to predict level of adult PTSD symptoms. This gene - environment interaction remained significant when controlling for depression severity scores, age, sex, levels of trauma exposure other than child abuse and genetic ancestry.

“The most novel and important finding of our study was the interaction between FKBP5 polymorphisms and child abuse history to predict the levels of adult PTSD symptoms,” the authors write. “These genotypes potentially serve as predictors of both risk and resilience for adult PTSD among survivors of child physical and sexual abuse.”

JAMA. 2008; 299[11]:1291-1305.