Credit: Emilia Stasiak

An international group of scientists is delving into the genetic basis of obsessive-compulsive disorder (OCD) using mice that are genetically engineered to lack the gene Sapap3, which is involved in neurotransmitter signaling. Deleting Sapap3 resulted in greater anxiety and compulsive grooming to the point of self-injury in these mice. Both the anxiety and excessive grooming were diminished when the mice were treated with a selective serotonin reuptake inhibitor (SSRI). SSRIs are commonly prescribed as treatment for OCD in humans but are effective only about half the time. The mice's behavior and response to SSRIs may be analogous to symptoms of human OCD.

Guoping Feng of Duke University Medical Center (Durham, NC) led the study, which included collaborators from China and Portugal and was published in Nature (doi:10.1038/nature06105, published online 23 August 2007).

Feng and his colleagues originally deleted the gene in mice as part of an investigation of neuronal communication in the striatum, an area of the brain that controls movement, decision-making and information processing. They noticed that all the Sapap3 mutant mice developed lesions on the head, neck and snout regions. The lesions began as hairless patches below the eyes or swelling of the snout and grew into wounds on both sides of the face covering large areas of the head and neck. The lesions were not caused by other mice or by pre-existing inflammation or skin defects. The mutant mice spent much more time grooming themselves than did wildtype mice without the gene deletion, even grooming themselves during the time when mice normally sleep. The researchers concluded that the mice were grooming themselves so excessively as to cause the lesions. Upon observing this compulsive-like behavior, they looked for and found other OCD-like symptoms in the mice, such as greater anxiety and response to SSRIs.

OCD is a relatively common psychiatric disorder in humans, present in roughly 2% of us. Its neurological basis is not well understood, but the circuitry in the cortico-striato-thalamo-cortical area of the brain is thought to be involved, in addition to genetic factors. OCD is thought to have multiple mechanisms of development. Feng tells Lab Animal, “Previous human studies of OCD have been mostly focused on serotonin and dopamine; our study indicates that defects in neurotransmission by glutamate play an important role in OCD-like behavior. This opens up a new area for research in identifying genes involved in OCD.” Feng also noted that this discovery could lead to new treatment strategies targeting glutamate-mediated neurotransmission.