OCD: Dobermans to the Rescue

A gene linked to obsessive-compulsive disorder in dogs could lead to a better understanding of the condition in humans

By Catherine O’Neill Grace

Doberman pinschers may hold the genetic key for understanding obsessive-compulsive disorder in humans. While one in 50 adults suffers from OCD, engaging in repetitive behaviors like uncontrolled hand washing, it turns out that up to 70 percent of Doberman pups in any given litter and some 8 percent of all dogs have obsessive tendencies, such as compulsively sucking their flanks.

“This discovery could provide a better understanding of disease biology and facilitate development of genetic tests,” the researchers said. Photo: iStock

In a breakthrough that could help explain human OCD and lead to better treatments or prevention for the anxiety disorder, researchers have located the gene for obsessive-compulsive disorder in Dobermans—the first behavioral gene identified in dogs.

Nicholas Dodman, director of the Animal Behavior Program at the Cummings School of Veterinary Medicine, and colleagues from the University of Massachusetts Medical School and the Broad Institute at MIT and Harvard found that Dobermans that exhibit compulsive behaviors have a gene, located on canine chromosome 7, that predisposes them to OCD.

“We don’t know for certain that it’s the gene that causes OCD in people, but what we did find out is that the same gene exists in humans on chromosome 18, which has the reputation of being the ‘psychiatric’ gene,” says Dodman, lead author on the research, published in the January 2010 issue of Nature’s Molecular Psychiatry.

The implications are profound. “This discovery could provide a better understanding of disease biology and facilitate development of genetic tests, enabling earlier interventions and even treatment or prevention of compulsive disorders in at-risk canines and humans,” the researchers wrote.

“The occurrence of repetitive behaviors and similarities in response to drug treatments in both canine compulsive disorder and human OCD suggest that common pathways are involved,” says Edward I. Ginns, director of the Molecular Diagnostics Laboratory at the University of Massachusetts Medical School and a study co-author.

“That moment changed our lives,” Nicholas Dodman says. “I decided that behavior was what I wanted to do.”

A Eureka Moment

Dodman’s interest in compulsive behaviors goes back nearly 30 years, when he joined the veterinary faculty at Tufts as an anesthesiologist. He and Louis Shuster, a pharmacologist and now professor emeritus at the Sackler School of Graduate Biomedical Sciences, started examining repetitive behaviors in horses. Their eureka moment came courtesy of a palomino horse named Poker’s Queen Bee.

The palomino was prone to cribbing, a behavior in which a horse grips an edge (a fence, grain bin or stall) with its front teeth, arches its neck and gulps in air—over and over and over again. “In some thoroughbred barns, over 30 percent of horses indulge in cribbing,” says Dodman. “I wondered why these animals, in the pressure cooker of modern domestic horse life, were doing this.”

He and Shuster already knew that when horses are given increasing doses of morphine, they begin to pace in circles. They hypothesized that cribbing horses might be responding to what Dodman calls “nature’s own morphine,” or the endorphins that their bodies release under stress. The researchers administered a morphine-blocking drug to Poker’s Queen Bee, and the horse’s cribbing stopped, suddenly and completely.

“That moment changed our lives,” Dodman recalls. “I decided that behavior was what I wanted to do.” Shuster, who had been studying drugs of abuse, focused his research on repetitive behaviors, and the horse’s owner left her high-profile executive job to pursue graduate studies in pharmacology.

Dodman went on to examine compulsive behaviors in cats and dogs, particularly in Doberman pinschers and bull terriers, which are also at risk for OCD. “Veterinarians had long observed dogs engaging in stone chewing, nail biting, blanket sucking, pacing and so on,” Dodman says. “They do all kinds of weird stuff. But nobody knew what was causing it.”

Dodman says the technology is in place to give researchers a better idea of how the genetic variations in dogs with canine compulsive disorder affect brain function—and to develop diagnostic tests and new treatments.

Now the research team is collaborating with scientists at the National Institute of Mental Health to determine how closely the genetic markers they identified are associated with a risk for human OCD and autism spectrum disorders, a developmental disability that hampers social interaction and communication.

Catherine O’Neill Grace, the editor of Tufts Veterinary Medicine, can be reached at catherine.grace@tufts.edu . For more information on the sequencing of the dog genome, visit www.broadinstitute.org/mammals/dog