Genetic Link to Common Mental Disorder Found in Mice
A genetic abnormality may help explain why some people are more prone to feelings of anxiety and aggression than others. Researchers say they've discovered a gene in mice that regulates levels of a chemical responsible for controlling anxiety, impulsive violence, and depression in humans.
Researchers say the gene, Pet-1, is active only in serotonin nerve cells in the brain. Serotonin is a chemical messenger that allows cells to communicate with each other in the brain and spinal cord.
When this gene was eliminated in laboratory mice, the researchers found that the mice displayed more aggression and anxiety.
The findings appear in the Jan. 23 issue of the journal Neuron.
Defective serotonin cells have been linked to anxiety and depression in humans. In fact, antidepressant drugs such as Prozac (Fluoxetine) and work by increasing serotonin levels.
But researchers say that until now, it was unknown whether a genetic defect causes these serotonin cells to malfunction.
This study suggests that Pet-1 is required for normal development of serotonin cells. Mice who didn't have this gene failed to develop enough serotonin cells in the fetus, and those that were produced were defective.
"This leads to very low serotonin levels throughout the developing brain, which in turn results in altered behavior in adults," says researcher Evan Deneris, PhD, neuroscientist at Case Western Reserve University in Cleveland, in a news release. This is the first gene shown to affect adult emotional behavior through specific control of serotonin nerve cells in the fetus, he says.
Researchers conducted anxiety and aggression tests on the mice lacking the Pet-1 gene and compared their behavior with normal mice. In an aggression test that measures a mouse's response to an intruder mouse entering its territory, the defective mice attacked the intruders much more quickly and more often than the normal mice.
For the anxiety test, the researchers measured the amount of time a mouse would stay in an open, unprotected area of a test chamber compared with a closed, protected area. Researchers say normal mice will enter and explore unprotected areas, but the mice lacking Pet-1 avoided this area entirely, which indicates abnormal anxiety-like behavior.
Deneris says if further research shows that Pet-1 is associated with excessive anxiety or violent activity in humans, then tests to detect the abnormal version of the gene might be useful for identifying people who may be at risk for these abnormal behaviors.
Source: Neuron, Jan. 23, 2003 - News release, Case Western Reserve University, Cleveland.