Other clues come from the hormone oxytocin, which courses through the brain during social interaction and has been shown to boost trust and reduce anxiety. In one imaging study, participants viewed frightening images after receiving nasal sprays of either oxytocin or a placebo. Those who sniffed oxytocin showed reduced activation in the amygdala and weaker connections between the amygdala and the brainstem, which control some stress responses, such as heart rate. The oxytocin surge that comes from being around other people could, like endorphins, help to reduce the stress response.
Past social interactions may also affect how a person responds to trauma. Chronic neglect and abuse unquestionably lead to a host of psychological problems and a greater risk of PTSD. Ressler, however, points to a factor that is well recognized but poorly understood: 'stress inoculation'. Researchers have found that rodents and monkeys, at least, are more resilient later in life if they experience isolated stress events, such as a shock or a brief separation from their mothers, early in infancy.
Ebaugh says that early stress — and the confidence she gained in conquering it — helped her to recover from her traumatic abduction. She was born with a condition that made her feet turn inwards. At age ten, she underwent surgery to rebuild her knees followed by a year of intensive rehabilitation. “It wasn't foreign to me to be hurt and have to walk the walk of being strong again,” she says. “It's like a muscle, I think, that gets built up.”
Resilient by nature
Although most people, like Ebaugh, recover from trauma, some never do. Some scientists are seeking explanations for such differences in the epigenome, the chemical modifications that help to switch genes on and off (see page 171). Others are looking in the genes themselves. Take, for example, FKBP5, a gene involved in hormonal feedback loops in the brain that drive the stress response. In 2008, Ressler and his colleagues showed that in low-income, inner-city residents who had been physically or sexually abused as children, certain variants in FKBP5 predisposed them to developing PTSD symptoms in adulthood. Other variants offered protection.
The most talked-about biological marker of resilience is neuropeptide Y (NPY), a hormone released in the brain during stress. Unlike the stress hormones that put the body on high alert in response to trauma, NPY acts at receptors in several parts of the brain — including the amygdala, prefrontal cortex, hippocampus and brainstem — to help shut off the alarm. “In resiliency, these brake systems are turning out to be the most relevant,” says Renu Sah, a neuroscientist at the University of Cincinnati in Ohio.
Interest in NPY and resilience took off in 2000, partly because of a study of healthy US Army soldiers who participated in a survival course designed to simulate the conditions endured by prisoners of war, such as food and sleep deprivation, isolation and intense interrogations. NPY levels went up in the soldiers' blood within hours of the interrogations. Special Forces soldiers who had trained to be resilient had significantly higher NPY levels than typical soldiers.
Researchers are now conducting animal experiments to study how NPY works. In one experiment, a team at the Indiana University School of Medicine in Indianapolis restrained a rat in a tight-fitting plastic pouch for 30 minutes, then released it into a box with another rat. The restraint made the rat so anxious that it avoided interacting with the other animal for 90 minutes. But when rats were injected with NPY before the treatment, they interacted with cage-mates as if nothing had happened.
The work could lead to treatments. Charney's group at Mount Sinai is carrying out a phase II clinical trial of an NPY nasal spray for individuals with PTSD. Others are investigating small molecules that can cross the blood–brain barrier and block certain receptors that control NPY release.