On Science

Tougher Than We Think

New study pinpoints a source of resilience to stress disorders

By Josie Glausiusz | December 17, 2014
Lauren Manning/Flickr
Lauren Manning/Flickr


Over the course of our lives, between 50 to 60 percent of us will experience a severe trauma, whether war, natural disaster, terrorism, rape, or violent assault. Although rates vary, one study shows that only about eight percent of people will develop post-traumatic stress disorder (PTSD) in the wake of such an adversity. Research over the past two decades has shown that resilience to major trauma is far from rare; so-called adaptive coping is more prevalent.

Neurobiologists and psychologists alike are actively investigating the behavioral, hormonal and genetic underpinnings of resilience. According to Steven Southwick of Yale University School of Medicine and Dennis Charney of Mount Sinai School of Medicine, the authors of 2012 review of resilience in the journal Science, it is known that repeated incidents of uncontrollable stress during infancy and childhood, such as child abuse, can affect brain development, leading to learned helplessness that can continue into adulthood. By contrast, “mild-to-moderate” stressors—over which a child can obtain a sense of power and control—can have a “steeling” effect that enhances resilience to future stress in adulthood.

Other factors associated with resilience, according to Southwick and Charney’s review, include strong social support, loving parental care, altruism, and “commitment to a valued cause or purpose [and] a capacity to extract meaning from adverse situations.” Genetics play a role as well: in particular, one version of a gene controlling reuptake (reabsorption) of serotonin (a chemical that transmits signals between nerve cells) is associated with an increased risk of depression following mistreatment in childhood.

Now, a team of researchers led by neuroscientists Caroline Dias, Jian Feng, and Eric Nestler of Icahn School of Medicine at Mount Sinai in New York City has identified a single protein in the brain that promotes resilience to chronic stress. The protein, beta-catenin, was discovered in the early 1990s. It is active in the brain’s reward and motivation center; mice that lack resilience to stress show a “dramatic deficiency” in its signaling activity.

In their new study, published in the November 13 issue of the journal Nature, the team engineered mice to “over-express” the protein in their brains. The rodents, researchers discovered, were resistant to the effects of a 10-day “social defeat stress” test. In the test, a mouse is placed for a few minutes inside a cage with a larger, more aggressive mouse. A screen is then placed between the two for the rest of the day, so that they can still detect each other by scent. While the over-expressing mice maintained normal social behavior, the mice deficient in beta-catenin “succumb to the bad effects of stress,” Nestler explained to me via phone interview. “They avoid other mice like them, including other females, they avoid sex, they avoid play, they avoid running wheels; they’re avoiding anything that has to do with interactions or playing with other mice,” he said. Such social avoidance, he added, is “a cardinal symptom of stress-related disorders in humans.”

When Nestler and his team autopsied the brains of people who had died during a period of depression, they found a similar suppression in the activity of beta-catenin in humans, as well. That indicates that the protein or the genes that it activates could be a new target for novel antidepressants that strengthen mechanisms of natural resilience. They are needed, Nestler said, because although the current generation of antidepressants “work fabulously well and save lives” they still work in only about half of all patients with a clearly described depressive syndrome.

The research also suggests a new approach to understanding how and why people recover from trauma, “enriching our ability to understand what is going wrong in people who can’t be resilient,” Nestler said. “The rates of PTSD are hotly debated—anywhere from 10 percent to maybe 30 percent in combat situations.” Even so, he added, “if you look at different populations around the globe, most humans are resilient, whether it’s combat settings, Holocaust survivors, people who survive various types of civilian trauma. What’s amazing is that large numbers of people do okay.”


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