As reported by The Hartford Courant, November 18, 2005.

Promise in the Anxiety of Mice for Men

By William Hathaway

Mice that lack the single gene stathmin lose their instinctual aversion to open areas and do not demonstrate anxiety when exposed to unpleasant conditions they have been taught to fear, according to a study published today in the journal Cell.

The gene appears to regulate both inherent and learned fears and may prove to be a goldmine for scientists who want to study the many facets of anxiety. If similar genes function in the same way in humans, they could form the basis for a new generation of anxiety drugs, experts said.

"This is one of those papers that open up a whole new chapter" of research, said Dr. Thomas Insel, director of the National Institute of Mental Health, which funded a portion of the study and which is part of the National Institutes of Health.

Fear is a primal emotion, one crucial to the survival of all animals. Broadly speaking, fears fall into two categories. Innate fears are specific to species. Mice, for instance, run from shadows and avoid open spaces, instincts that help them avoid predators. Life-threatening or painful events can trigger the formation of learned fears. Also essential to survival, learned fears are easy to establish and can last a lifetime.

In human terms, an innate fear hardwired in the brain might make you jump at the sight of a snake, while learned fear, which grows out of experience, could help you jump away from a speeding car.

Scientists have long identified areas of the brain that are crucial to the fear response in animals and in humans. A central player is the amygdala, an almond-shaped region of the brain that processes emotions such as anger and fear. Researchers looking for the genetic basis of fear zeroed in on proteins found in abundance in the amygdala.

Several years ago, researchers at Rutgers University and Columbia University found a gene in the amygdala called gastrin-releasing peptide, or GRP, that helps regulate learned fear, but not innate fear.

That same group of researchers discovered that stathmin seems to regulate both.

"`Knockout' mice, which lack the gene, show a decreased memory for [learned] fear," said Gleb Shumyatsky of Rutgers, lead author of the study.

Nor did they seem as fearful of heights or open spaces, which they normally fear out of instinct.

The ability of mice lacking stathmin to complete tasks, such as finding a platform in a water maze, did not seem to be affected.

Researchers trying to determine the molecular basis of many types of behavior have been largely limited to studying the effects of neurotransmitters such as dopamine or serotonin, but, Insel said, "it looks like there are a whole bunch of [other mechanisms] we didn't know about."

It is not known whether the gene plays the same role in humans as it does in mice. Researchers note, however, that the amygdala is a primitive organ preserved in all mammals.

Down the road, such genetic investigations may prove beneficial in understanding anxieties and phobias in humans, said Dr. Nicholas DeMartinis, assistant professor in the department of psychiatry at the University of Connecticut School of Medicine.

DeMartinis pointed out that about a third of people with anxiety disorders can suffer from several different disorders, and genetic tests might allow psychiatrists to make better treatment decisions.

He also noted that children of people with anxiety disorders tend to have children with similar disorders. With knowledge gleaned from the discovery of the gene, DeMartinis said, "We might be able to intervene at an earlier stage, and prevent problems before they arise."