Genes and Posttraumatic Stress

Why is it that when a group of soldiers share a horrific battle experience, some are able to work through it and get on with their lives, while others suffer the persistent anxiety, emotional numbness and bomb-blasted nightmares of posttraumatic stress disorder (PTSD)? The answer, researchers have long believed, is that an individual's response to trauma — whether in battle or as result of a natural disaster, violent crime or some other horror — depends not only on the intensity of that trauma but also on a complex interplay of past experiences and genetic factors. A new paper, published in the current issue of the Journal of the American Medical Association, provides remarkable support for this explanation and identifies a specific gene that influences susceptibility to PTSD.

The study, led by a team at Emory University, looked at 900 adults — most of them low-income and African American — seeking medical care at two clinics in Atlanta. A history of trauma is common in poor, urban populations, and the researchers found that 80% of the subjects had been exposed to trauma, with the great majority exposed to multiple traumatic stressors in their lives. "Over a third said they had a friend or family member murdered," says Dr. Rebekah Bradley, assistant professor of psychiatry and behavioral science at Emory. About 30% had been abused as children — a well-established risk factor for developing PTSD.

When the subjects were evaluated with a psychiatric questionnaire for symptoms of PTSD, 25% met the criteria for the disorder. "That's a rate almost as high as among returning combat veterans," says Bradley, who also directs a PTSD treatment team at the Atlanta Veterans Affairs Medical Center.

The research team collected saliva samples from each subject and looked at a gene known as FKBP5, which influences the body's response to the stress-related hormone cortisol. "When it's working right, it helps to down-regulate the stress response system," explains Bradley. Different individuals have slightly different versions of this gene, varying by a single nucleotide (or letter in the DNA alphabet). The researchers found that four variants of the gene were associated with an increased rate of PTSD in individuals who also had a history of child abuse. Other variants seemed to confer some protection or resilience. Between 26% and 33% of the subjects had one of the high-risk gene patterns and between 17% and 24% had a pattern associated with resilience to developing PTSD, with the largest group somewhere in the middle.

All told, these tiny differences in the genetic code seem to influence whether an individual with a childhood history of abuse rises above it or struggles psychologically when exposed to traumas later in life.

The PTSD study adds to a growing body of research showing that genes influence whether an adult who experienced childhood abuse later develops mental illness. "What we're finding across the board is that what we've inherited makes us more or less vulnerable to the impact of childhood abuse," says Bradley. "Certain genes can either amplify or dampen the impact of the abuse."

The study raises the question of whether soldiers going into combat or others who work in high-risk situations could some day be screened for vulnerability to PTSD. "It's possible that super-high-risk groups might want to do this kind of screening — special forces, for example. But right now the science isn't there yet," says Dr. Thomas Neylan, director of the PTSD program at the San Francisco Veterans Affairs Medical Center. And, he adds, it may be impossible to predict vulnerability with precision.

Neylan points out that the research may have implications for developing drugs to treat PTSD. The role of the FKBP5 gene suggests that it might make sense to target the specific molecules that regulate the body's response to stress, he says.

Both Neylan and Bradley say the research underscores the powerful interplay between childhood trauma, genes and mental health. Childhood abuse is a risk factor for multiple mental illnesses, including depression, eating disorders and substance abuse as well as PTSD. "If we could simply reduce childhood abuse," says Bradley, "it would have a major impact on mental health."