From The Quarterly, Fall 2010

NARSAD investigators have discovered a gene that may be central in the development of symptoms in Obsessive-Compulsive Disorder, or OCD. Symptoms include repetitive behaviors from hand-washing to ritualistic counting of numbers and are associated with increased anxiety.

The team investigated the genetic link to behaviors and also measured corresponding brain activity with brain scans.



In examining the role of a gene called Slitrk5 in mouse stem and blood cells, NARSAD Independent Investigators Francis Lee, M.D., Ph.D., and Sergey Shmelkov, M.D., along with Shahin Rafii, M.D., all of Weill Cornell Medical College, created a mouse model in which the Slitrk5 gene was deleted or “knocked out.” They were surprised to notice that these mice lacking the gene displayed increased anxiety behaviors, including excessive self-grooming. The mice began to show symptoms at three months of age and also displayed altered brain activity similar to that documented in brain scans of people suffering from OCD.



This NARSAD-funded research team is the first to provide an animal model that accurately mirrors the specific brain regions that are disrupted in OCD. The fact that these investigators discovered this model by altering a single gene is more than noteworthy: Most psychiatric disorders are associated with multiple genes, making this a rare find and one that could make better treatments for OCD a reality if Slitrk5 is found to be involved in the disorder in humans.



Drs. Lee and Shmelkov took their discovery to the next level and made another intriguing discovery. They were able to prevent mice lacking the Slitrk5 gene from overgrooming by giving them the SSRI (selective serotonin reuptake inhibitor) antidepressant fluoxetine, commonly known as Prozac and widely used in the treatment of OCD.



This finding could prove to be important because it points to the Slitrk5-deficient mouse as a very good model for OCD in humans. Discovering models of human illness in animals effectively provides researchers with living systems in which to test promising new treatment ideas — ideas that cannot be easily tested in people, for a variety of ethical and regulatory reasons.



The team says, in this case, an important next step is clear — to examine the Slitrk5 gene in people with OCD. If levels of the gene’s activity, or expression, is abnormal in actual sufferers of OCD, new treatments could be developed, first in mouse models, to target pathways affected by the disorder.