Not everyone is vulnerable to post-traumatic stress disorder (PTSD)--the extreme anxiety, depression, and nightmares that can follow a harrowing event. Although some people develop symptoms after seemingly minor traumas, others can handle wars, hurricanes, or various forms of physical abuse without losing their emotional balance. Now, researchers have shown that mutations in a stress-related gene may help determine whether someone who suffered from abuse as a child is susceptible to PTSD later in life.
Teasing out the genetics of PTSD has been difficult. Children who are abused are more susceptible to PTSD as adults, and researchers estimate that up to 40% of this susceptibility is inherited. But just what genes are responsible is not known. One promising lead is FKBP5, a gene that helps regulate binding between stress hormones and their receptors. Research has shown that childhood abuse can lead to overreactivity in the body's stress response system, so a team at Emory University in Atlanta, Georgia, decided to see if there was a link between PTSD and mutations in FKBP5.
The researchers collected data on 762 people, most of them from poor black neighborhoods, who came to the clinic over a 2-year period for nonpsychiatric reasons. Through interviews and questionnaires, the subjects reported experiences with childhood abuse as well as other types of trauma in later life. Clinicians determined whether such traumas had triggered PTSD in adulthood. Subjects also gave saliva samples so their DNA could be tested.
Some 30% of the patients reported physical or sexual abuse, or both, as a child. This group showed twice the number of PTSD symptoms following later traumas, such as an accident or robbery, as those who had not reported being abused. And the prevalence of two particular mutations in the FKBP5 gene were significantly more common in this abused group among those who had PTSD than those who did not. The mutations by themselves do not predict PTSD, showing that it's the combination of certain genes with the early trauma that leads to the vulnerability. The researchers theorize that some of the mutations make brain cells in children more sensitive to stress hormones throughout their lives.
The findings, reported today in the Journal of the American Medical Association, are complex and preliminary but "biologically plausible," says Richie Poulton of the University of Otago in Dunedin, New Zealand, an expert on gene-environment interactions. It's an "important paper," adds psychiatrist Daniel Weinberger of the National Institute of Mental Health in Bethesda, Maryland. The work is part of an emerging body of research "showing that genes for complex psychiatric conditions are best studied in the context of other risk factors," he says. "I think this is the wave of the future."