Mice tests yield clues on human disorder

Paris — Scientists have stumbled on a mouse gene which, when disabled, provokes behavior similar to the anguishing human condition known as obsessive-compulsive disorder (OCD), according to a study released Wednesday.

When the gene is reactivated, or when the mice are given drugs used to treat the syndrome in people, the compulsive actions diminish, says the study, published in the British journal Nature.

The discovery suggests new strategies for treating the disorder, which affects nearly two percent of the world’s population, more than 100 million people.

Famous sufferers include 18th-century English writer Samuel Johnson, American magnate Howard Hughes, and — by his own admission — celebrity footballer David Beckham, who said he obsessively stacks up cans of soft drinks.

A team of researchers led by Duke University molecular geneticist Guoping Feng discovered the link between the gene, known as SAPAP3, and compulsive behavior by accident while conducting basic research on the striatum, a portion of the brain that controls the planning and execution of movement.

In normal brains, the SAPAP3 protein facilitates the transfer of nerve signals across synapses from one nerve cell to another, helping them communicate via the glutamate messenger system.

Glutamic acid is thought to be crucial to cognitive functions like learning and memory.

"When we looked closely at the brain cells of these mutant mice" — which had been genetically modified to suppress the gene — "we found that there were defects in the synapses," Feng said in a statement.

As a result, the mice engaged in compulsive grooming until their faces were raw, and also exhibited anxiety-like behavior, hiding in corners and hesitating to take risks.

But when the gene was switched back on, "the synaptic defects were repaired and their OCD-like behaviors subsided," Feng said. The researchers also found that a class of drugs known as selective serotonin reuptake inhibitors, also used to alleviate the symptoms of obsessive-compulsive disorder, worked almost as well, establishing an even stronger link to humans.

Like SAPAP3, serotonin is a chemical involved in nerve communication in the brain.

While Feng’s mutant mouse could prove to be a useful model for studying OCD in humans and the development of new drugs, many problems remain, noted Harvard neurobiologist Steven Hyman in a commentary, also published in Nature.

"It is highly unlikely that such animal models will ever recapitulate human psychiatric disorders in their entirety," he wrote, pointing out that the main cause of anxiety in OCD patients is unwanted intrusive thoughts.

"Sufferers are anxious because they cannot be sure the door is locked, the gas has been turned off, or that they are free of deadly microbes," a fear that leads to the emblematic symptom of continuous hand-washing.

It requires a stretch of the imagination, he suggests, to think that mice experience comparable feelings.

Moreover, like other major psychiatric disorders, OCD probably stems from a mix of chemical imbalances along with developmental and environmental factors, reducing the role that a single gene might play. — AFP


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Mice tests yield clues on human disorder