Researchers Discover Biological Pathway Linked to PTSD


In both men and women with PTSD, the PAC1 gene was more likely to be modified by a process call "methylation," meaning people are not necessarily born susceptible to PTSD but can acquire the vulnerability over time. The finding supports the idea that environmental, genetic and so-called epigenetic factors all contribute to PTSD risk.

To confirm their discovery, Ressler and his colleagues studied PACAP signaling in mice trained to fear a particular sound. This so-called fear conditioning led to genetic changes, including a 1.5-fold boost in PACAP receptor expression, in regions of the brain involved in fear. Estrogen had a similar effect, according to studies done in rats.

Promise for Treatment?

Anyone can get PTSD -- including war veterans and survivors of assault, abuse, accidents and disasters. More than 10 percent of U.S. Army soldiers return from deployment with PTSD or major depression, according to a 2010 study published in the Archives of General Psychiatry. Some people can suffer from PTSD after the trauma or death of a loved one, even if they were not directly involved in the event.

"We hope some of these biomarkers may actually be predictive of who is at risk for PTSD," Ressler said.

Although psychotherapy and certain medications work for some, many people with PTSD develop chronic panic disorder, depression and even suicidal tendencies. Ressler hopes his research translates into new, more effective treatments or preventions that target specific fear pathways in the brain. But whether the PACAP pathway holds therapeutic promise needs to be confirmed in larger samples and in different types of trauma.

"At the early stages of a discovery there's always excitement but also apprehension as one waits for it to be replicated by others," Ressler said.

In an accompanying editorial, Dr. Murray Stein, a professor of psychiatry and family and preventive medicine at the University of California, San Diego, suggested the possibility of a PTSD risk profile that "takes into account psychosocial and biological factors, much like those available for predicting the risk of coronary heart disease."

"Even if PACAP is not it, this proof of principle study shows that developing a reliable biomarker for PTSD is not a pipe dream," Stein wrote.

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