Finding of compulsive behavior gene in dogs has implications for humans

From The New York Times:

Scientists have linked a gene to compulsive behavior — in dogs.

Researchers studied Doberman pinschers that curled up into balls, sucking their flanks for hours at a time, and found that the afflicted dogs shared a gene. They describe their findings — the first such gene identified in dogs — in a short report this month in Molecular Psychiatry.

Dr. Nicholas Dodman, director of the animal behavior clinic at the Cummings School of Veterinary Medicine at Tufts University, in North Grafton, Mass., and the lead author of the report, said the findings had broad implications for compulsive disorders in people and animals.

Estimates have obsessive-compulsive disorder afflicting anywhere from 2.5 percent to 8 percent of the human population. It shows up in behavior like excessive hand washing, repetitive checking of stoves, locks and lights, and damaging actions like pulling one’s hair out by the roots and self-mutilation.

The disorder has been used in popular movies and television shows to define characters like the reclusive writer Melvin Udall, played by Jack Nicholson, in “As Good as It Gets” and Adrian Monk, played by Tony Shalhoub, in the television series “Monk.”

Similar disorders are known in dogs, particularly in certain breeds, including Dobermans.

Dr. Dodman and his collaborators searched for a genetic source for this behavior by scanning and comparing the genomes of 94 Doberman pinschers that sucked their flanks, sucked on blankets or engaged in both behaviors with those of 73 Dobermans that did neither. They also studied the pedigrees of all the dogs for complex patterns of inheritance. The researchers identified a spot on canine chromosome 7 that contains the gene CDH2 (Cadherin 2), which showed variation in the genetic code when the sucking and nonsucking dogs were compared.

The statistical association led to further investigation to determine for which protein the gene contained instructions. It did for one of the proteins called cadherins, which are found throughout the animal kingdom and are apparently involved in cell alignment, adhesion and signaling.

Cadherins have also been recently associated with autism spectrum disorder, which includes repetitive and compulsive behaviors, said Dr. Edward I. Ginns, senior author of the report in Molecular Psychiatry and director of the Molecular Diagnostics Laboratory at the University of Massachusetts Medical School.

Dr. Dennis Murphy, a psychiatrist who was not associated with the study, said the results had the potential to advance understanding of obsessive-compulsive disorder. Dr. Murphy, also chief of the Laboratory of Clinical Science in the National Institutes of Mental Health’s Division of Intramural Research Program, is now working on finding and sequencing the CDH2 gene in humans to see whether it is linked to obsessive-compulsive behavior.

People with obsessive-compulsive disorder often engage in normal behavior that has become extreme, ritualized, repetitive and time-consuming, and suffer from anxiety and obsessive thinking.

Because the disorder involves obsessive thoughts and because of the difficulty of understanding animal cognition, the same kinds of behavior in animals has commonly been referred to simply as compulsive disorder.

As scientists learn more about the underlying molecular causes of this condition, they increasingly use “obsessive-compulsive disorder” to apply to animals and people.

Recent rough estimates by Dr. Karen L. Overall, a veterinarian specializing in animal behavior at the University of Pennsylvania School of Medicine, suggest that up to 8 percent of dogs in America — five million to six million animals — exhibit compulsive behaviors, like fence-running, pacing, spinning, tail-chasing, snapping at imaginary flies, licking, chewing, barking and staring. Males with the problem outnumber females three to one in dogs, she found, whereas in cats the ratio is reversed.

Dr. Overall said dogs usually developed compulsive behavior between ages 1 and 4. Some of the Dobermans in Dr. Dodman’s group began earlier, with blanket sucking at around 5 months and flank sucking at 9 months.

Dogs can be treated, but if they are not, compulsive behavior is one of the main reasons that people give them up for adoption or euthanasia, according to veterinary behaviorists.

Dr. Overall said in an earlier paper that environmental causes might outweigh genetic factors in development of compulsive behaviors in some cases.

She said the practice of “hanging” a dog up by its choke collar, a form of discipline advocated by some trainers, produced compulsive behaviors. Dogs from puppy mills or shelters, rescue dogs and those that are confined and bored dogs or anxious also seem prone to compulsive behavior, she said.

Other domestic animals, notably cats and horses, as well as some of the animals at zoos, exhibit compulsive behaviors, including wool-sucking in Siamese cats, and locomotion disorders like stall walking and weaving in confined horses and pacing in captive polar bears, tigers and other carnivores used to ranging across large territories.

Although antidepressants, particularly selective serotonin reuptake inhibitors and clomipramine, a tricyclic antidepressant, and behavior modification have proved effective at controlling compulsive behavior in dogs and people, they do not appear to correct underlying pathologies or causes, Dr. Ginns said. Those causes are likely to be as varied as the compulsive behaviors and as complex as the interplay of multiple genes and the environment.

“Stress and anxiety, as well as physical trauma and illness, can trigger repetitive behavior that then takes on a life of its own,” Dr. Ginns said.

But he believes that in many cases there is an underlying genetic predisposition that responds to environmental stimuli in such a way that once-normal behavior turns into something pathological. Those genetic dispositions may differ markedly between different behaviors.

Some geneticists say that because of their detailed pedigree and the similarity of their genes to those of humans, dogs make an ideal model for studying human behaviors and pathologies, especially those involving complex patterns of inheritance. Few humans keep detailed genealogies for themselves, but they are diligent in recording every detail in the ancestry of their purebred animals.

“Nick and I share an interest in pedigrees,” Dr. Ginns said in explaining how he and Dr. Dodman became collaborators with Kerstin Lindblad-Toh and her gene sequencers at the Broad Institute of M.I.T. and Harvard, the same group that sequenced the dog genome now proving so valuable to both human and canine geneticists.