Gene mutation linked with obsessive behavior

Mice born without a key brain protein developed obsessive compulsive symptoms that went away when treated with anti-anxiety drugs, giving new clues about the brain mechanism behind the disorder, researchers said on Wednesday.

They said mice that lacked the gene SAPAP3, which makes a protein that helps nerves communicate, groomed their faces until they bled and developed an aversion for bright, open spaces.

"We think they cannot control themselves," said Guoping Feng, a molecular geneticist at Duke University Medical Center whose study appears in the journal Nature.

Feng said these behaviors resembled those of humans with obsessive compulsive disorder, also known as OCD.

The anxiety disorder is marked by intrusive thoughts and repetitive compulsive behaviors, such as frequent hand washing, which disrupt daily life. OCD affects up to 2 percent of the world's population.

Feng and colleagues had been focusing their research on the function of the protein made by the gene SAPAP3. They bred mice that lacked the gene.

Initially, these mice were normal but after four to six weeks they developed raw patches on their faces. Videotapes revealed compulsive grooming.

Further testing showed the mice were excessively anxious. When placed in a dark box with a door leading to bright open spaces, normal mice would venture out but mice that lacked the protein remained inside the box.

"They feel the bright place is the riskier environment," Feng said in a telephone interview. "This is additional evidence that they have increased anxiety."

When the researchers restored the missing gene, the mice behaved normally.

Fluoxetine, an anti-anxiety drug sold by Eli Lilly and Co. under the brand name Prozac and used to treat OCD symptoms in humans, also relieved the symptoms.

Feng said the study was the first to suggest that a defect in the part of the brain called the striatum can cause OCD symptoms.

SAPAP3 is part of a family of proteins that regulate the neurotransmitter or message-carrying chemical glutamate. Feng believes this neurotransmitter may be a useful target as companies develop new drugs for anxiety disorders.