Obsessive Compulsive Mice

May 2, 2010

 It’s hard to picture a mouse with mental health issues, but in their own tiny way, mice can suffer from at least one psychiatric condition: obsessive-compulsive disorder (OCD). Thanks to a new discovery from Weill Cornell Medical College in New York City, scientists may now be able to use that fact to help humans struggling with the same debilitating condition. The Weill Cornell team, headed by molecular biologists Dr. Shahin Rafii, Dr. Francis Lee and Dr. Sergey Shmelkov, had not initially set out to study OCD. Instead, they were conducting research on the role of a gene known as Slitrk5 in the development of stem cells that eventually specialize into blood cells. To understand the function of the gene better, they engineered mice in which Slitrk5 was disabled (or “knocked out”). They then looked for how it affected the animals’ bloodstream. The verdict: it didn’t. But that didn’t mean the mice were unchanged. Before long, the knockout mice began developing curious lesions around their mouths. In addition, they became unusually anxious and jumpy — even by mouse standards. On closer examination, the mice appeared to be engaging in hyperactive grooming behavior, far more than normal mice do and more than enough to cause the facial injury they were suffering. Other species of animals have been known to display similarly excessive grooming behaviors. Parrots compulsively pluck their own feathers; dogs repetitively lick a paw or other fixed spot; humans develop a condition known as trichotillomania, in which they pull out strands of their hair. All of these behaviors are thought to fall along the OCD spectrum, though of course the disorder is much more complex in humans. It’s characterized by intrusive, obsessive thoughts (fear of being contaminated by germs, for instance, or anxiety about whether the door is locked) and compulsive behaviors intended to relieve the anxiety caused by those obsessions (hand-washing, counting and other repetitive behaviors). The Slitrk5 gene, which exists in humans as well as in mice, appears to plays a role in the release and uptake of glutamate in the brain, a neurotransmitter that helps regulate urges. In the knockout mice, researchers found the greatest irregularities in the frontal cortex and the striatum — the gene was excessively active in one part of the frontal cortex, while the level of glutamate receptors in the striatum was decreased. In humans, the frontal cortex–striatum circuit is involved in laying down memories and processing rewards that may later guide the planning and control of behavior; it makes sense that dysfunction here could be related to the uncontrollable urges and behaviors of OCD. Earlier studies have also linked variations on the Slitrk5 gene to Tourette’s syndrome, a condition characterized by involuntary tics, vocalizations and even shouting of obscenities. Some doctors place Tourette’s along the OCD spectrum too — though admittedly at a far end.