Bouncing Back from Stress: Scientists Identify the Brain’s Way of Protecting Against Stress

Researchers at the Mount Sinai School of Medicine have identified a substance in the brain that helps protect against stress and reduce susceptibility to depression. Identification of the gene regulating substance, called deltaFosB, is a major step forward in analyzing the brain wiring that can help or hinder our ability to cope with stress and to avoid depression. The identification of this gene regulator also helps to explain how certain antidepressants work.

The substance is what neuroscientists call a “transcription factor.” That means that it controls more than one gene, turning multiple genes on and off by generating the proteins that tell genes what to do. As a transcription factor, deltaFosB plays a complicated role in a whole circuit of systems in the brain related to stress.

The study, reported online in the journal Nature Neuroscience, found that deltaFosB controls a complex reward system in the brain. When mice were subjected to stress, if they had sufficient levels of deltaFosB to trigger this “resilience circuit,” they were less likely to suffer from symptoms of depression. The Mount Sinai researchers studied the same circuit in human brains and found that when deltaFosB is increased, the human brain is also protected from the kinds of stress that may produce depression.

In fact, the brains of depressed people seem to have as little as half as much deltaFosB as the brains of people who are not depressed. Without deltaFosB, some antidepressants, like Prozac, can not perform well. The scientists also learned that spending long periods of time away from social contact can decrease the production of deltaFosB, explaining why people who are isolated might be more likely to become depressed.

Although the identification of deltaFosB is an important step in understanding the brain chemistry of depression, more research is needed before therapies making use of this gene regulating molecule will be possible. Specifically, the researchers are now trying to locate compounds that produce or assist the production and operation of deltaFosB. The study may ultimately lead to a new group of more effective antidepressant medications, which will be based on a greater understanding of how the healthy brain protects against stress and depression.