September 16, 2014 -- While abnormalities in the adrenergic and noradrenergic systems, both integral in the fight-or-flight response, are thought to play a role in the development of post-traumatic stress disorder (PTSD), until now there has been no genetic evidence of this connection. A collaborative study just released by researchers at Columbia University's Mailman School of Public Health and the University of Michigan found an interaction between the ADRB2 gene and childhood adversity. For individuals with two or more experiences of childhood trauma, such as abuse, genotype was associated with risk for adult PTSD symptoms. These findings are significant for the study of the physiology of PTSD, for the treatment and prevention of stress-related illnesses, and may have implications for treating pain, which has also been linked to the ADRB2 gene.
This is the first report of genetic risk factors for PTSD in National Guard soldiers and adds to the developing evidence base on the role of genetic influences in PTSD. Findings are online in JAMA Psychiatry.
The researchers analyzed results from 810 Ohio National Guard soldiers who took part in the Ohio National Guard Study of Risk and Resilience, all of whom reported having experienced a potentially traumatic event in their lives. Nearly three-quarters of the guardsmen had been deployed to combat zones including in Iraq and Afghanistan, and 42 percent had seen active military combat. Service members were asked about their childhood exposure to experiences of physical, sexual, or emotional abuse, or witnessing of violence between parents. Soldiers were further asked about adult trauma, including 33 categories of deployment-related and non-deployment events, and then evaluated for PTSD symptoms using a 17-item PTSD checklist. A replication cohort of predominantly African-American female civilians enrolled in the Grady Trauma Project in Atlanta was evaluated for childhood adversity, adult trauma, and PTSD symptoms in a similar fashion.
"We found strong evidence that the ADRB2 gene SNP (defined as Single Nucleotide Polymorphism) was associated with PTSD in our group of male soldiers who were predominantly of European American ancestry," said Sandro Galea, MD, DrPH, chair of Epidemiology at the Mailman School of Public Health and senior author. "Of particular note is the finding that the identical interaction took place in the control group of civilians. Together these outcomes suggest that the ADRB2 gene interacts with childhood adversity and either result in a vulnerability or resilience to developing PTSD symptoms following adult trauma."
Soldiers with the AA genotype of the rs2400707 SNP, located in the promoter region of the ADRB2 gene were the most resilient to adult PTSD symptoms, given exposure to two or more types of childhood adversity; those with the AG genotype had an intermediate risk of adult PTSD symptoms, and those with the GG genotype had the greatest risk of adult PTSD symptoms. No differences by rs2400707 genotype were observed for those with less than two types of childhood adversity. This suggests that having two or more types of childhood adversity may represent a different childhood experience during critical developmental periods, according to Galea.
The question of whether the genetic risks for developing PTSD are similar in other populations that are exposed to different traumas at different periods in their lives remains to be further tested, noted Galea. "However, our findings that the ADRB2 factor might be shared by men and women, African Americans and European Americans, and military and civilians is consistent with the idea that some genetic risk factors for PTSD might be common across populations and even shared by other stress-related disorders, such as depression."
Lifetime trauma exposure was also a strong predictor of PTSD symptoms, regardless of rs2400707 genotype. This was not unexpected since epidemiologic studies have identified severity of trauma exposure as a major risk factor for PTSD. In the current study, significant interaction between genetic variance and lifetime adult trauma exposure was not observed. "This suggests that genetic variance in interaction with childhood trauma alone can influence adult PTSD symptom severity," said Galea.
"By understanding how PTSD develops, we are better positioned to employ effective prevention and intervention strategies in the military and beyond," said Israel Liberzon, MD, University of Michigan Professor of Psychiatry and first author of the study. "With these data, we will help patients suffering from the strains of PTSD earlier on, and prevent unnecessary pain, suffering and stress."
"While additional investigations are clearly needed to confirm the existing findings and identify new ones, these data provide an important lead for both examining the pathogenesis of PTSD and developing specific and effective prevention and intervention strategies," noted Galea.
The research was supported by grant W81XWH-10-1-0579 from the Congressionally Directed Medical Research Programs, Department of Defense.
About Columbia University's Mailman School of Public Health
About Columbia University's Mailman School of Public Health
Founded in 1922, Columbia University's Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 450 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,300 graduate students from more than 40 nations pursuing a variety of master's and doctoral degree programs. The Mailman School is also home to numerous world-renowned research centers including ICAP (formerly the International Center for AIDS Care and Treatment Programs) and the Center for Infection and Immunity. For more information, please visit http://www.
About University of Michigan Health System
For more than 160 years, the University of Michigan Health System has been a national leader in advanced patient care, innovative research to improve human health and comprehensive education of physicians and medical scientists. The three U-M hospitals have been recognized numerous times for excellence in patient care, including national rankings in many specialty areas by U.S. News & World Report.