Genetic Fear Factor Discovery May Help Fight Mental Illness

Scientists have identified a specific gene variation that sparks heightened activity in the brain’s “fear center”--the first gene identified to affect a function of the brain related to human emotion, according to researchers at the National Institutes of Health.

The gene activates the amygdala, a portion of the brain that controls its response to frightening situations, and has been weakly linked to increased anxiety.

David Weinberger, chief of the Clinical Brain Disorders Branch at the NIH, said the research is a key step in understanding the complex biological puzzle of human temperament.

“Genes don’t create personality, but they give you the building blocks. This is one building block of personality,” said Weinberger, director of the study published today in the journal Science.

Ahmad Hariri, lead author and a staff fellow at the NIH, is quick to point out that they have not discovered the “anxiety gene.” This gene is part of a complex system for determining how people feel fear, Weinberger said. “There are lots of factors in how people react to fearful stimuli,” he said. “One of those is genetic.”

The gene in question is part of the serotonin system, a brain messaging chemical that has been implicated in mood. There is a naturally occurring variation in the gene--a short form and a long form. Those with a shortened version have less of a protein, called the serotonin transporter, “that is like a vacuum sucking the serotonin out of the synapses,” Weinberger said.

There have been previous studies showing that people with the short form of the gene are more anxious, but the results are far from conclusive, Weinberger said.

Evaluating anxiety can be a very subjective process, he said. Add that to the complexity of the genetic system involved, along with the many environmental factors that contribute to anxiety, and it becomes difficult to assess the effect of a specific gene.

Weinberger and colleagues decided to look at a more direct measure of the gene’s effect--the activity of the amygdala.

The amygdala is a small, almond-shaped section at the bottom of the brain that “turns on and off when the environment is dangerous,” Weinberger said.

To spark activity in the amygdala, NIH researchers showed people pictures of frightened faces--a standard method used to evoke the brain’s fear response.

People instinctively feel afraid when they see a scared human face, Weinberger said. Even infants show this reaction.

The team used functional magnetic resonance imaging, or fMRI, to see how actively the amygdala responded to frightened faces. They found that people with the short form of the gene had a “hyperactive” amygdala.

“This inherited variation of the gene sets the volume control of the amygdala a little higher,” Weinberger said. “They’re a little louder in response to dangerous signals in the environment.”

Michael Davis, a professor of psychiatry at Emory University in Atlanta who studies the amygdala’s relationship to fear, said the findings will help in understanding why some people tend to be more anxious. The results are a “good lead” that genetic variation of the serotonin system is involved in anxiety, Davis said.

“The gene by itself is no guarantee” that someone will suffer from anxiety or depression, Weinberger said. But it could be a factor that contributes to susceptibility to anxiety.

One of Weinberger and Hariri’s goals is to understand what makes some people more susceptible to mental illness.

The gene under study is involved in the neural pathway targeted by the antidepressant Prozac. People with the short form of the gene respond better to Prozac. Weinberger and Hariri plan to look at how Prozac affects the activity of the amygdala in these individuals.