The Resiliency Gene

Why are some children able to bounce back from trauma and abuse, while others suffer with depression and mental problems throughout their lives? The answer may be partly in the genes, according to a new paper published in the Archives of General Psychiatry. One variant of a gene called CRH1 seems to protect kids from the long-term effects of physical, sexual or emotional abuse. In kids who aren't abused, the gene doesn't have any influence on risk of depression later on. But abused children with the "resilient" variant have a relatively low risk of developing depression as adults, whereas abused kids with another variant are more likely to suffer from the disorder.

"You see these kids who go through the worst experiences and they seem to come out stronger, whereas other kids come out bruised," says Thomas Insel, director of the National Institute of Mental Health. "The way they're responding to loss or traumatic events is partly encoded in their genomes."

The new paper is one in a series published over the last four years that have "resolved a long-term debate," says Insel. Scientists have tried to pinpoint single causes for depression and other mental illnesses, often with little success. "For 100 years we've argued about depression: is it nature or is it nurture? When you look at something as complicated as depression, if you just look at genes or just look at environment, the effects aren't there. But if you look at them together, you start to see these interesting interactions. Studies like this are getting us beyond nature versus nurture to understand how nature interacts with nurture. It's a very different discussion now."

The new study focuses on the brain's CRH1 receptor, which responds to corticotropin-releasing hormone, a chemical that controls the fight-or-flight response. "There are all kinds of reasons to think the CRH receptor could be important for the biology of depression," says Insel. The amygdala, the brain region associated with fear and other intense emotions, is loaded with CRH receptors. Levels of the hormone seem to get set, like a thermostat, in infancy and childhood. "Early activation of the receptors could change the way they work and how sensitive they are," says Insel. "They have these imprinting effects where you often see very long-term consequences."

In abused kids, says Kerry Ressler, a lead author of the study and an assistant professor of psychiatry at Emory, the CRH system seems to get turned up in response to mistreatment, becoming hyperactive. No one knows how or why. "These [hormone] systems are supposed to prepare you for dealing with a lifetime of stress. They get hardwired early on," says Ressler. "It's possible that the wiring in an abused kid is somehow protective at the time the abuse is taking place." Later, however, that wiring may get stuck in a pattern that makes the brain vulnerable to depression.

Several previous papers have linked other genes to child abuse and the risk of mental problems later in life. The most heavily studied gene controls the brain's ability to process and use serotonin. "This gene comes in two flavors, a short one and a long one," says Insel. "By itself the short one doesn't increase your risk of depression. But if you put it together with traumatic events, bingo—you're more likely to be depressed. Most people now see that as the paradigm for understanding the cause of depression." Another gene, which controls the brain's use of a chemical called monoamine oxidase A (MAOA), also seems to make people more likely to become antisocial as adults if they are subjected to "harsh discipline, physical abuse or other forms of maltreatment" as kids, according to a 2006 paper. Kids with the short MAOA gene who aren't abused, however, are at no greater risk of antisocial behavior later on.