Yikes! A single gene appears to modulate the amygdala’s response to emotional faces.

A Gene for Fear

Compared to eye color and pattern baldness, linking genes and behaviors has been a tough nut to crack. A new study in the 19 July issue of Science makes a substantial dent: It shows that versions of a single gene can influence how the brain responds to emotion-laden stimuli. The finding could help explain why one version of the gene seems to make people prone to anxiety.

The gene in question encodes a transporter protein that shuttles the neurotransmitter serotonin back into neurons after it has been released. The gene comes in two common versions, or alleles. One contains a short promoter region (the stretch of DNA that controls the gene's expression); the other has a longer promoter. An early hint that the transporter gene influences behavior came from the finding that people who have a copy of the short allele are slightly more likely (3% or 4%) to show signs of anxiety or fearfulness on clinical personality tests than are those with two copies of the long allele.

A team led by psychiatrist and neurologist Daniel Weinberger of the National Institute of Mental Health in Bethesda, Maryland, reasoned that the gene's effect might show up more clearly in the brain's emotional command center: an almond-shaped region called the amygdala. The researchers used functional magnetic resonance imaging to monitor activity in the amygdalas of 28 volunteers. While being scanned, subjects saw a picture of a face with either an angry or frightened expression and then had to choose which of two other faces showed the same emotion.

Both groups matched expressions correctly about 90% of the time. But people with at least one copy of the short allele showed considerably more activity in their right amygdalas while engaged in the task. "The amygdala puts a label on information that says 'This is dangerous,' " Weinberger explains, and a hyperactive amygdala might explain why people with the short allele are more prone to anxiety.

"It's a fascinating study," says Joseph LeDoux, a neuroscientist at New York University. "It will surely stimulate lots of additional work on the neural basis of normal and pathological fear and anxiety."