Is OCD in the Blood?

A different gene in a different pathway might be involved in OCD as well, based on findings by HHMI investigator Shahin Rafii of Weill Cornell Medical College in New York City and colleagues.

While searching for genes switched on in stem cells, the researchers discovered a gene family, the Slitrks, whose functions were mysterious. One of these genes, Slitrk5, is active in blood vessel cells and blood stem cells. Rafii and colleagues deleted the gene from mice to nail down what it does.

To the team’s surprise, mice missing Slitrk5 resembled Capecchi’s mice and OCD patients. Like Capecchi’s animals, the rodents washed so often that they tore out their fur and injured their skin. Anxiety is a typical OCD symptom, and the mice were timid, even for rodents. As the researchers reported in the May 2010 Nature Medicine, the mice curbed their grooming after treatment with Prozac (fluoxetine), a common therapy for OCD.

The mice also showed telling brain changes. The orbitofrontal cortex, a region at the front of the brain that is responsible for decision making, was hyperactive. Meanwhile, the striatum, which sits farther back in the brain, was smaller than normal, and it contained fewer of the glutamate receptors that dampen neural activity. Rafii suggests that in OCD patients, the undersized striatum can’t prevent the overactive orbitofrontal cortex from firing off too many signals. The result could be compulsive behavior.

Because Slitrk5 is present in the blood cells, this could be another case in which non-nerve cells trigger OCD behavior. To test this hypothesis, Rafii’s team has transplanted bone marrow from normal mice into Slitrk5-deficient mice to determine whether normal blood cells curb the animals’ excessive grooming. They expect to have the answer by next year.

-- Mitch Leslie
HHMI Bulletin, November 2010

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