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Psycho Dogs 

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

Wednesday, Mar 7 2007
At four in the morning, Melanie Chang was sitting up in bed, singing along to Madonna's "Crazy for You." She stared at the dog crouching on the floor of her bedroom, a wild-eyed creature too scared to sleep. Melanie was not crazy for him. She was not even sure if she would keep him.

She met Solo a few weeks before, in September 2000. It was not love at first sight.

Solo was too big, and the wrong color, she thought — a rangy mess of reddish-brown and white fur. He didn't seem to think much of Chang, either. He found the grass at the dog park more interesting than her, and gave it a good sniffing.

She was in mourning for her wee puff of a Pomeranian, who had succumbed abruptly to cancer that summer. Dogless and confused, she signed up haphazardly with various purebred dog rescues, organizations that recycle dogs booted from their homes. She could have ended up with a Siberian husky or a basenji, an African hunting dog. She thought a Shiba Inu, a Japanese breed, might be fun. Instead, the first reply came from a man with a border collie.

Chang had never seen a border collie, though she knew a fair bit about them; as a kid she wasn't allowed to have a dog, so she read breed encyclopedias instead. She knew they were smart, demanding, and active. An average border collie is a lot to handle. Chang was about to meet a dog that would be a good candidate for a straightjacket.

The man wrote that he was trying to place a 16-month-old dog who had suffered through a traumatic puppyhood, and had been through at least four homes in the last two months. Expecting a casual and preliminary conversation, Chang met the man and the dog at a nearby park. Usually, getting a dog from a rescue organization requires a long application process, with references, home visits, the works. This was different.

"You want to give this a try?" asked the man. It was like he was anxious to get the dog off his hands.

"I did think to myself, "Something is not right here,'" remembers Chang. "But I actually heard this voice in my head that said, "Just let this happen.'"

The man handed her the leash, and Chang and Solo walked home together. Solo still hadn't deigned to notice her. Chang felt numb.

"A few hours later I realized he was cracked," she says.

Today, Solo is also known as No. 256; he's one of about 3,000 dogs whose DNA has been collected and analyzed at a lab at UCSF's Langley Porter Psychiatric Institute. Chang is at the lab, too, but as a researcher, not a subject. She wound up at the lab because of Solo's "issues."

Dr. Steve Hamilton runs the basement laboratory in a building on Parnassus Avenue, where he hoards doggy DNA in industrial-strength refrigerators and freezers.

Hamilton is a psychiatrist who wants to know what role genes play in the devilish list of mental disorders that plague human beings; his current work includes a genetic analysis of people with panic attacks, and a study of patients' varied responses to the antidepressant Celexa. Now, with an unusual project, he's turning to another species for insight into abnormal brains and behavior.

They call it the dog study — or, officially, the Canine Behavioral Genetics Project. Hamilton is recruiting dogs that hide under the bed during thunderstorms, dogs that get anxious or aggressive with strangers, dogs that obsessively chase their tails, and dogs that chew up shoes, pillows and couches when they're left alone for hours. Many people believe that such dogs are misbehaving; the classic "bad dogs." Hamilton essentially says that these dogs are mentally ill, and hypothesizes that the key to their behavior is in their genes.

Hamilton believes that dogs are natural models for the study of human mental illness, as there are clear parallels between the species. Veterinarians say they see dogs with anxiety and panic attacks, obsessive-compulsive disorder, separation anxiety, and phobias, all disorders that humans also suffer from. In dogs, these behavior disorders can be observed and measured easily. "When humans are anxious, there's a stereotypical constellation of symptoms — they're tremulous, they pace, they're withdrawn, they have an elevated heart rate," Hamilton says. "Dogs have similar symptoms that you can observe — they pant, salivate, defecate."

Still, why not cut to the chase and look for the genetic component of these disorders in humans? The answer has everything to do with the legendary zeal of dog fanciers, who have, over many generations, created well-defined breeds with very distinct genetic profiles. "Dogs are the grand genetics experiment that humans have carried out for the past 10,000 years," Hamilton says.

Humans have carefully tended to the canine breed stock, sometimes selecting for physical attributes, like a Dalmatian's spots or a poodle's tight curls. But in past eras, breeders tried to enhance behavioral traits, building border collies to herd sheep, golden retrievers to fetch game, and greyhounds to hunt rabbits. Humans have created breeds with incredibly specific behavior patterns — which means looking into their genomes offers an unprecedented view into what makes dogs act the way they do.

If Hamilton can discover which genes are connected to mental disorders in dogs, then his results can eventually be translated into human terms, and give medical researchers leads on gene therapies to treat disorders like anxiety. But in the short term, his research will be discussed mostly by the dog world of owners, trainers, and breeders. His work will become part of an ongoing argument about "crazy dogs," and whether they're a result of innate genetic defects or flawed upbringing and training. While Hamilton stresses that the answer is never simply one or the other, it seems clear that he'll prove that there is indeed a strong genetic component in dog behavior disorders. What's not yet clear is what the repercussions will be.

In the next few years, the dog world will have to find its way through the dense, tangled nature-versus-nurture debates that tied human psychiatry in knots over the past decades. Dog owners will argue over whether psychotropic drugs are miracle cures or just shortcuts for the lazy owner; already veterinarians are seeing the dawning of Doggie Prozac Nation.

Hamilton expects that there will be fierce resistance to the idea that training is not the ultimate answer to bad behavior in dogs. "Have you seen the Dog Whisperer, on TV?" he asks. "The idea is, by force of will, you can always get a dog to do what you want. If you can't, then the owner must have done something wrong." Similarly, he says, human psychiatrists long refused to believe that some people were born with an inherited risk of developing mental illness, and blamed the patients' environments. "Stereotypically, the idea was, it's the mother's fault," Hamilton says. "In the dog world, the idea is that it's all the owner's fault. My vet colleague jokes that they're about 20 years behind us."

When Chang got ready for bed that first night, Solo got nervous; he began pacing around the bedroom and whining. Then she turned off the light, and he started to howl — a high-pitched scream, the sound of acute distress.

She turned the light back on, sat up, and looked at him. He stopped pacing and crying, and looked back. She turned off the light and lay down. He started to howl again. "Dear God!" thought Chang.

Soon she discovered that if she talked to Solo, he would settle down on the floor. But he wouldn't fall asleep, and he wouldn't let her stop talking. After about four hours, "I kind of ran out of things to talk about," she says, so she started singing to him. That's where Madonna came in. But he wouldn't let her stop singing: "He'd wake up and start howling, and then I'd sing something else — it just kept going like that all night," she says.

Chang would soon realize that her pup had full-blown separation anxiety, which explained his nighttime anxiety in a weird way. "He was afraid to be alone, and I guess when I went to sleep, it was like I was going away in his mind," says Chang.

The next day, she brought Solo to the University of Pennsylvania with her; she was a graduate student studying physical anthropology and evolutionary biology. Her little Pomeranian had gone to school every day, either waiting patiently in Chang's shared office or grinning and wagging through classes. Chang hoped Solo would do the same. She brought him to the office, introduced him to her office mate, and took off for class. "Five minutes later my adviser came to get me and said, "Your dog is wigging out!'" she says.

Over the following days, Chang began to understand the severity of Solo's problems. She set up a tape recorder in her apartment and left to see what happened in her absence: Solo started screaming 30 seconds after the door clicked shut, and didn't stop for the 45-minute duration of the tape. She skipped work to stay with him, and either skipped classes or brought him along — although that wasn't ideal, either, since he'd sometimes sit up and start howling for no obvious reason. "It was really disruptive to my graduate school career," she says wryly.

It was more than Chang had bargained for. She e-mailed the man who had passed Solo on to her. "This dog is crazy!" she wrote indignantly. The man wrote back making "the appropriate noises" about how much he hoped it would work out — but he didn't offer to take Solo back.

Meanwhile, advice was coming in from all sides. One common opinion was that Solo was just a bad dog. He was the wrong dog for her. There was something defective about him. He should be put to sleep. "You will get tons of positive reinforcement if you decide to kill your dog," Chang says. Another refrain was that she should find an "animal communicator" to get some insight into Solo's mental state, a suggestion that the science-minded Chang didn't take seriously. But she couldn't help wishing that a medium could whisper into Solo's ear, and get answers in return. "The first thing I would have asked is, "What the hell is the matter with you?'" she says.

At the Golden Gate Kennel Club's annual show in late January, thousands of people packed the Cow Palace to admire more than 130 varieties of dog-dom represented. Several halls were packed with vendors who took cutesy to a new, horrifying level: One shop offered throw pillows embroidered with pictures of corgis in tutus. Hamilton's booth stuck out; next to a booth full of pet portraits, all lolling tongues and wet eyes, Hamilton's team had hung enlarged copies of their scientific papers.

The Canine Behavioral Genetics Project's tent was stocked with questionnaires and little brushes used to scrape cells off the inside of a dog's cheek. Hamilton's team was looking for recruits to donate dog DNA. They talked up the importance of the project to every owner who paused in front of their display: Do it for science, do it for a better understanding of our canine companions. They explained to an owner that she won't get results back; she won't find out what her poodle's DNA looked like, or why he acts the way he does. Someday, if Hamilton's work goes well, vets will give dogs DNA tests and screen for behavior disorders, but that's years down the line.

Chang made a foray into the crowd to hand out kits to the owners and breeders showing border collies. The 25-page questionnaire has detailed inquiries about how the dog reacts to certain stimuli: When there's a thunderstorm, for example, how does the dog respond? Does he salivate, defecate, urinate, destroy things, try to escape, hide, tremble, howl, pace, or simply freeze? Owners fill out the form, dutifully scrape the inside of their dog's cheek, and send it all back. Hamilton's lab then extracts the DNA from the cheek cells and starts rummaging through the genomes of dogs that display certain traits.

Serious devotees of purebred dogs have grown accustomed to studies of dog genetics in the last two decades, as it became clear that inbreeding has had serious medical consequences. Breeders find inbreeding useful for bringing out desirable recessive traits; they'll sometimes mate closely related dogs in order to get a rare coat coloring, for example. Unfortunately, breeders may be selecting for less obvious recessive traits as well. It's common knowledge that they have inadvertently created Rottweilers prone to hip dysplasia, Dalmatians with kidney problems, narcoleptic Dobermans, and Portuguese water dogs at risk of blindness. Forward-thinking breed clubs have developed DNA databases to aid research into inherited diseases, sometimes even funding the studies.

But so far, breeders have been much more reluctant to study behavior disorders — just as in human society, there's stigma attached to mental illness. Some experts believe breeders are avoiding the subject because they don't want to be held responsible when a dog loses its marbles.

Jean Donaldson, an author and a dog trainer at the San Francisco SPCA, is one of the country's leading experts on dog behavior. She sees dogs with every conceivable behavior issue, and owners at the end of their ropes. Some dogs' problems she attributes to the immediate genetics of their family lines; like the Shar-Pei who had such severe separation anxiety that he broke his teeth and bloodied his paws trying to gnaw through the doorframe when his owners left. Donaldson says she usually recommends medication for such extreme cases. "You know, dogs are routinely euthanized for things like separation anxiety. So it seems to us that the lesser of two evils is to go ahead and medicate," she says.

Donaldson's office is crowded with two dogs, her own fluffy chow chow, Buffy, and a foster chow chow she's calling Buttercup. The foster dog was abandoned in the SPCA's parking lot, a shy, nervous mess with matted fur, skin problems, and a broken tooth. The city shelter deemed her "unhandleable," so Donaldson is trying to rehabilitate Buttercup and make her eligible for adoption. Buttercup's tangled fur has been shorn and she now wears a cozy pink coat, but she still cringes away from people. She had clearly been mistreated, which partially explains her anxiety, but Donaldson says that chows are known as a nervous breed; Buttercup got the one-two punch of nature plus nurture. Donaldson had made an appointment with the vet to discuss medication.

Most commonly, she sees dogs with aggression problems. While she's a fierce opponent of "breed bans" like the proposed outlawing of pit bulls that San Francisco debated two years ago, she believes it's undeniable that some breeds are predisposed to violence. Many breeds that were bred as guardians or fighting dogs were carefully designed to not like strangers, she says. She thinks it's disingenuous of breeders to further enhance this trait, and then expect owners to compensate with training.

"I think the biggest implication of genetics and behavior is that breeders are going to end up being implicated," she says. She mentions a chocolate Labrador with compulsive disorder, whom she's treating, that was bred from field trial champions. He compulsively fetches and guards household objects, and chewed at his tail until the owners were forced to amputate the tip. "It's a classic case of genetics kicking in, so predictably! Unbelievably predictably!" Donaldson says. "It's very frustrating to throw every med in the book at this dog, when somebody built him to be this way. Should we really be building dogs to have compulsive disorders?"

When Chang had stopped feeling sorry for herself and accepted that she had a "whacko dog," she started making phone calls, and eventually pieced together Solo's sad life story.

Solo was born at a shabby kennel in central Pennsylvania where the dogs, chained to the doghouses, wore muddy circles in the ground by pacing. He had eight weeks of happily squirming over his littermates before he was sold to a woman who kept a stable of purebred stud dogs; she made a nice profit by renting out their services. But the dogs weren't useful until they matured, so she locked Solo in a kennel in the backyard and left him there for a year. He got little or no training, exercise, or human affection. "He was basically veal for a year," Chang says.

Chang doesn't know why, but when Solo was 13 or 14 months old the owner of the stud farm started trying to sell him — but he kept getting returned, like a defective product. He went to a family that ran a day care in the house, but he herded the children, and got sent back. Another family said that he barked all day while he was tied up in the back yard. A third owner let Solo run loose on a farm, but couldn't stop him from chasing the horses.

Solo's penultimate stop was a ranch in Maryland that trained working sheep dogs. The owners thought that even if Solo wasn't suitable as a pet, they might be able to train and sell him as a working dog. But he was afraid to go after the sheep. Chang speculates that he had been punished for chasing horses, which left him wary about the whole herding thing. "He flunked out of herding school," she says.

The man who gave Solo to Chang was the only border collie rescue volunteer who was willing to take him — and now he didn't want Solo back. Chang realized that she was the end of the line for the dog. Her friends thought he was a "hairy beast," and told her there was clearly something wrong with him. No one would have blamed her if she had brought him to a shelter to be euthanized. He would barely eat, and his ribs were sticking out. When he wasn't agitated, he was nearly catatonic: Chang would wave her hand in front of his glassy eyes, and he wouldn't even blink.

"Everybody who has a dog like this has the same story," Chang says. "You feel sorry for yourself at first. You think, there's this universe of perfect dogs out there, how the hell did I get stuck with this crazy one?"

Chang remembers the day she decided she had to keep the sad, scrambled dog. Sleep-deprived, she was rambling through a pet supply store, looking for dog food that Solo might actually eat. She looked from a bag of kibble to the animal at her knees, and saw a drooling, pathetic animal who looked like he was waiting for someone to kill him. It was too much for her kind heart to resist, and she dropped down to give him a hug.

"I didn't want to be the last person to give up on the dog," she says. "I thought, everybody else has let him down, and I just can't."

The dog study is a collaboration between Hamilton, who brings his expertise in human psychiatry and genetics, and Karen Overall, a veterinarian behaviorist at the University of Pennsylvania who pioneered the use of psychotropic medications in dogs. She vividly recalls the 1989 case that started her experiment. Spinner was a medium-sized mutt, your average city dog with some shepherd in him. His owners were despondent when they brought him in; they loved their dog, but had no idea what to do.

"This was a dog that couldn't stop staring at its feet and snapping at his feet," Overall explains. "And he would look around, and see a shadow, and he'd start to look worried, and he'd snap at the shadow. And then he'd look at his feet again, and try to pull his feet back, and then he'd spin in a circle."

Although the traditional method of treatment would be to ask about his environment and his training, Overall was convinced that the dog had a case of obsessive-compulsive disorder. "There was no way on God's Earth that people could have caused the dog to be like that," she says. So she marched over to the university's psychiatry department and sought out the department chair. She described her patient's symptoms, announced that she thought the dog should be treated with medication, and then braced herself for derision. Instead, she got a list of drugs and doses used to treat OCD in humans.

Overall called the drug company that made the human medication she wanted to try, and talked them into giving her a free supply. Then she began treatment, combining medication with behavior modification exercises — much the same way humans combine drugs and therapy. It did the trick. The medication didn't turn Spinner into a glassy-eyed zombie, as the owners feared, and it didn't instantly solve all his problems. But it calmed the dog down enough so that he could focus on something besides his own distress, which allowed the new training to take hold.

"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.

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."

If Hamilton can identify genetic markers that signify an increased risk of noise phobia, anxiety, and other behavior disorders, it will be a great boon for the dog world. As part of routine checkups, vets could analyze blood samples and screen for dogs that are likely to develop behavior problems. They could then counsel the owners of vulnerable dogs to intervene early, with either meds or behavior modification training.

However, those are solutions for dogs who are already damaged, the results of centuries of breeding experiments carried out in ignorance of the possible consequences. Hamilton's work also points to a way to reverse this process. Responsible breeders could check their dogs' DNA, and refuse to breed those who have the genes associated with behavior problems. By removing vulnerable dogs from the gene pool, they might eventually be able to create happier, more stable breeds. That's what the SPCA's Donaldson is hoping for. "Dog breeders could probably put me out of the fear and aggression business in 20 generations," she says.

Here's where human psychiatry and dog psychiatry finally diverge. Nobody with any moral sense would suggest that human mental illness should be eliminated by restricting who can reproduce. In dogs, it's a possibility that's fast approaching. Dogs, welcome to the Brave New World.

About The Author

Eliza Strickland


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