Root of Obsessive-Compulsions Found in Mice
> 8/24/2007 11:53:42 AM

Mice enjoy exercise wheels, but when they run on one for unending hours, there is a problem. Duke researcher Guoping Feng discovered this problem, which appears similar to the obsessive-compulsive disorder that plagues 2% of the human population, when he noticed that strangely behaving mice lacked the protein SAPAP3 due to a genetic mutation. There is still a debate about whether OCD has a genetic cause, but this finding, along with the earlier twin research by Rasmussen, may be enough to close the case.

SAPAP3 helps signals travel across synapses like a neural ferryman. This protein is produced most prolifically in the striatum, an area of the brain that translates complex plans into the small steps that make up movement. It has been speculated that OCD behavior is caused by a confusion about whether a plan was actually carried out; the desire to lock the door cannot be sated if part of your brain never gets the message that the key was actually turned and the task completed. When researchers looked at the striatum of the mutated mice, they observed wide-scale malfunctions. Even with the naked eye, the malfunctions were obvious. Mice turned normal face-washing into a painful ritual that was not satisfied until paws brought up blood.

The mice's compulsive face-washing seems perfectly analogous to human OCD hand-washing, and continued experimentation with medication provided further confirmation of the similarity. Artificially replacing SAPAP3 in the striatum alleviated the mice's compulsive behavior, as did the administration of selective serotonin reuptake inhibitors. SSRIs are the most commonly prescribed medication for OCD in humans.

These mutated mice are a fortuitous discovery. If they are suffering from OCD, then any work to help them will be work to help ourselves. SSRIs fail to relieve symptoms in almost half of cases, so a more precisely targeted drug is necessary. If further research reveals the exact reason for OCD in mice and men, we may be able to develop a consistently effective treatment.

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