Psycho Dogs

What makes canines go crazy? The answer is in their genes.

"When something new happened, like there would be new people over for dinner, he would start to look all worried and begin to stare at his feet again," Overall says. But what once seemed pathological now seemed like a manageable behavior quirk. If his owners gave him some extra reassurance, Spinner would lift his gaze from those menacing toes, and sit calmly through dinner.

In the 18 years since then, Overall has seen a dramatic shift in what owners and veterinarians are willing to do for troubled dogs. Vets used to chuckle about "doggie psychiatrists," she says, but now she gets calls from vets begging her to make time for their clients.

The pharmacological revolution is well under way. There are several drugs already licensed specifically for dogs, and last month Eli Lilly announced a new form of Prozac to treat separation anxiety in dogs. The drug, sold under the name Reconcile, is part of the company's new "companion animal sector." Like human Prozac, the doggie drug increases the amount of a neurotransmitter, serotonin, in the brain. It can have similar side effects to the human medication as well, sometimes causing lethargy or poor appetite.

At a local dog show, Steve Hamilton's team recruited purebred dogs for a genetics study.
Paolo Vescia
At a local dog show, Steve Hamilton's team recruited purebred dogs for a genetics study.
Rebecca Terrill scrapes off a few cells from this dog's cheek at the dog show.
Paolo Vescia
Rebecca Terrill scrapes off a few cells from this dog's cheek at the dog show.

Chang and Solo have benefited from the new medicines available, as well as from Overall's expertise. Chang was getting her Ph.D. at the University of Pennsylvania, and as the fates would have it, Overall was her adviser's wife. Overall prescribed Solo's medication and taught Chang some training exercises to decrease Solo's fear of being left alone. A few years later, when Hamilton was looking for a post-doc to work on the Canine Behavioral Genetics Project, Chang was a natural fit. She moved west in 2005.

These days, Chang stuffs two "non-crazy pills" into Solo's mouth every morning; he's on low doses of both Prozac and Elavil. When they lived in Pennsylvania, he also had a prescription for Xanax, which she'd give him if there were thunderclouds in the sky, but in San Francisco the weather patterns have been friendlier to her dog. Solo still doesn't like it when she leaves him alone in the apartment; when she's getting ready to go, he sits by her and looks as cute and plaintive as he can. "But it's not to the point where it seems pathological anymore," she says.

At Hamilton's basement lab at UCSF, the dog DNA samples have been arriving faster than his team can process them. More than a dozen small plastic boxes sit waiting on a lab bench near Chang's workstation, which is decorated with glamour shots of Solo. Every box holds about 70 plastic vials, each of which contains a swab carrying cheek cells. Isolating the DNA in those cells is a labor-intensive process; the lab technicians spend hours squirting in reagents and sending the vials whizzing around the centrifuge to dissolve the cells and remove extra proteins. Only then can Hamilton's team get to the interesting work of analyzing the DNA.

They've recently started studying border collies with noise phobia, a disorder that can range from quirky to life-threatening. Some border collies react fearfully to certain odd noises, like a dog Jean Donaldson knew that looked terrified when he heard pita bread being broken. Others are scared of the typical big bangs, like gunfire, fireworks, and thunderstorms. Chang has friends in Maryland whose dog was driven crazy by the region's summer storm season. The dog tried to jump out windows during storms, so they began putting him in his crate when it got cloudy; then he broke all his teeth trying to get out of the crate. His owners finally put him to sleep, recognizing that he was no longer enjoying his life.

Chang has leveraged her knowledge of the border collie world for this study, recruiting research subjects at breed club events, sheep-herding trials, and on Internet newsgroups. The work has paid off; they now have DNA samples from many extended border collie families. On the wall of Hamilton's office, several sheets of paper piece together one family tree whose members are scattered across the East Coast. The sire was an accomplished working dog who reportedly freaked out during thunderstorms and went bonkers on the Fourth of July. He was bred to five different dams; sure enough, the litters were peppered with noise-phobic dogs.

Hamilton doesn't know which genes are involved with noise phobia, so he's taking the general approach, looking at the entire genomes of individual border collies, and comparing them. The trick comes in deciding which dogs to compare. He can take two related dogs, only one of which has noise phobia, and look for the places where their genomes differ. Or he can take two unrelated dogs that both have noise phobia, and look for where their genomes are similar. Hamilton expects that it will take about 18 months before they can point to specific genes that they think are involved in the disorder.

The project has occasionally brought scorn from his psychiatric colleagues. "They say, "Why should we care, or more importantly, why should we fund this?'" he explains. "We need to convince the [National Institutes of Health] that understanding the health of dogs will illuminate human health. A side benefit is that we'll help dogs lead happy lives."

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