Genetic Link To PTSD Could Lead To Vet Drug Treatment

A recent study that discovered a genetic link to Post Traumatic Stress Disorder (PTSD) could ultimately lead to breakthroughs in treatment or prevention, but advances are at least a decade away because additional research is needed, according to the study’s top researcher.

Ultimately, there could be significant implications for the military where PTSD prevalence is estimated to be at least twice that of the general population because of severe trauma associated with combat duty.

“We’re onto something important,” said Mark W. Miller, the lead researcher. Miller is a clinical research psychologist in Boston for the VA’s National PTSD Center, and is an associate professor of psychiatry at Boston University School of Medicine.  But he said studies with more participants that replicate his findings are needed before talking about “policy implications or screening or anything like that.”

Dr. Joel Gelernter, a Yale psychiatrist and chief of the VA’s Molecular Genetics lab in West Haven, was not involved in this study, but does research on the genetics of PTSD. He said if the Boston study results are replicated in future research, then it opens the possibility for much-needed, new drug development for treatment of PTSD.

“Drug development is a very promising avenue for research if this line of evidence pans out,” Gelernter said, adding that now, there is “nothing really fantastic” available to treat PTSD.

According to Miller, the study, which began in 2006, is the first of its kind for PTSD because it was genome-wide, which means it analyzed the entire genetic makeup of participants, giving researchers 1.5 million pieces of genetic data per person.

It was conducted by the Veterans Administration’s National Center for PTSD and the BU School of Medicine. Researchers interviewed and took DNA samples from about 500 participants comprised of veterans and their spouses or partners.  All participants have experienced trauma, and about half have PTSD.

Participants with PTSD were found to share a variant of a gene known in scientific shorthand as RORA.  The same variant had previously been linked to a range of other psychiatric conditions, including bipolar disorder, autism, depression and attention deficit hyperactivity disorder.

Patrick Bellon, executive director of the advocacy group, Veterans For Common Sense, said the study is significant for veterans.  “We are glad to see research that furthers our understanding and possible treatment options for PTSD,” he said. “This research is more important than ever with approximately 1 million new veterans returning to civilian life in the next five years.  A complete understanding of this invisible wound of war, which afflicts at least 20 percent of veterans will be crucial to a successful transition for our service members.”

Gelernter, professor of psychiatry, genetics and neurobiology at the Yale School of Medicine, said, “One of the most exciting things about this study and studies of this kind is they can provide a new window into the biology of this disorder and that is really an exciting possibility.”

“Where it leads, we really don’t know yet, but it might lead to really exciting things,” he said.  “Treatment would be the most valuable,” he added.

Miller said if his study is sufficiently replicated, the next step would be genetic imaging research which would use the RORA finding to discover new biomarkers relevant to PTSD with ultimate goals that could include developing new treatments and methods for screening and assessments.

“The VA, for example, which compensates veterans for disabilities, would like to put somebody through a lab test that would unequivocally show who has PTSD and who doesn’t. With a psychiatric disorder, you can’t take an x-ray and see the broken part.  It’s possible that by bringing in genetic information, we might actually be able to identify who shows the brain changes and better understand the different patterns of brain response in PTSD,” he said.

But, he stressed, such an advance is still in “the realm of scientific speculation.”

According to the study, less than 10 percent of the general population develops PTSD after experiencing a traumatic event compared to estimates of 20 to 35 percent in the military.

In its 2012 policy agenda, the advocacy group Iraq and Afghanistan Veterans of America (IAVA) cites both the 2008 Rand study called “Invisible Wounds of War” which found that nearly 20 percent of Iraq and Afghanistan veterans screened positive for PTSD or major depression, as well as a Stanford University study which “found the number may be closer to 35 percent.”

The VA-BU study involved veterans averaging 51 years old and included people who served as long ago as World War II to veterans of the Iraq and Afghanistan wars. They were mainly Caucasians from Massachusetts and New Mexico.

About two-thirds of the participants were male and one third, female. Miller said additional research, including a study which he is undertaking, is being conducted to determine if women veterans are more likely to suffer from PTSD than men.

The VA-BU study defines PTSD as “profound disturbances in cognitive, emotional, behavioral and psychological functioning that occurs in response to a psychologically traumatic event.”

Symptoms include:  re-experiencing the trauma through intrusive thoughts, nightmares, flashbacks and other reactions to reminders; avoidance and emotional numbing; and hyper-arousal, exhibited in anger, hyper-vigilance, exaggerated startled response, and sleep disruption.
Veterans in the study experienced trauma mainly in combat while their civilian spouses faced trauma in everyday life such as through deaths of loved ones, natural disasters, accidents and sexual assaults.

Researchers found what Miller called “a partial replication” in a study done in Detroit, but participants were mainly African-American, compared to the mainly Caucasian subjects in his study.  In genetics research, the focus “at least initially, is on one particular ancestral group,” he explained.