The Dog Who Couldn’t Stop Licking
May all that have life be delivered from suffering.
Even if you haven’t personally had experience with pets who have licked, chewed, or rubbed themselves raw in places, you might have seen it in other people’s pets. The condition can appear ghastly. The natural impulse is to look away.
Most dogs that lick themselves raw have allergies, but there is also a condition called lick granuloma, a very specific type of compulsive behavior that is directed only at the lower extremities of the limbs, above the foot but below the elbow or knee. These areas are termed acral, a medical term for “affecting the extremities.”
For a long time, back in the Dark Ages before researchers began to unlock the secrets of animal behavior, vets and owners alike treated all irritated, furless patches on dogs with salves and ointments. These treatments can help sooth allergies, but with compulsive acral licking, they miss the point. Lick granuloma is not disease of the skin. It is a problem of the mind.
After Dr. Lou Shuster and I investigated compulsive behavior in equine subjects like Poker’s Queen Bee and Mobey, we wanted to know whether our findings in horses could apply to other animals.
So we turned our attention to dogs. Although the veterinary profession’s roots are in cattle doctoring, in today’s world canines have pride of place in examination rooms and animal hospitals. There are 78 million dogs living in American households. Lou and I asked ourselves, What behavioral condition do dogs have that are like cribbing: repetitive, apparently mindless, and seemingly pointless? In other words, what ways did dogs display compulsive behaviors?
Lick granuloma immediately came to mind. In response to constant licking, the skin erodes. In the normal process of healing, tiny blood vessels form and new connective tissue gradually fills in the wound. This healing process is one of the wonders of life—in humans, dogs, and other animals. But in lick granuloma, this process goes awry producing exuberant mounds of pink granular connective tissue bulging from the sore. This happens because the affected dog does not allow the healing process to run its natural course, and constantly irritates the wound by the licking. Sometimes, a deep ulcer forms and infection can track deep into the underlying tissues, including bone.
Lick granuloma is also referred to as acral lick dermatitis. The location of the licking and resulting abrasion is fairly specific and usually on the wrist (foreleg) or hock (hind leg). These are the locations where the dog’s head comes to rest if he tends to lie down flat on his chest, paws in front of him, or curled around on his side with his chin resting on his hock.
To test our theory that lick granuloma was natural behavior gone wrong, Lou Shuster and I repeated our experiments using morphine antagonists on dogs who had various forms of self-directed licking, scratching, or chewing. The dogs responded as the horses did—they reduced the harmful behavior. Clearly the drug’s action—and the underlying biochemical mechanism—was not just a “horse thing.” We then used the same drugs on cats who chewed blankets, stripped out their hair, or had other relentless neurotic habits. The cats, too, responded well.
At the time we were involved in our research, the behaviors we were treating were considered stereotypies—that is, rhythmic, repetitive, fixed, purposeful movements that occur in an animal that had otherwise developed normally.
But to call acral licking a stereotypy describes the symptom—yes, of course it’s a repetitive act!—and does nothing to get at root causes. Back then, the behaviors were not considered compulsive disorders. No one knew what triggered them and few vets knew how to treat them.
Acral licking is painful to watch, and many owners of pets with the affliction react with the same kind of frustration triggered by a cribbing horse. They take it personally and go to vets in despair. “How can I get my dog to leave off this constant, maddening, stop-it-already-will-you! He’s just doing it to annoy me!”
Many vets tried, but standard approaches of the day didn’t work. Dogs and cats were fitted with “Elizabethan collars” to prevent them from licking or chewing. These triggered a lot of blundering into furniture and perhaps some embarrassment in the pets, but upon removal of the collars the behavior recurred. Vets sprayed the affected areas with substances like bitter lemon that tasted or smelled bad, to try to repel the dog from licking. They injected an analgesic and corticosteroid combination to numb and soothe the injured skin areas, thinking that the dog would then not be so conscious of pain or irritation in the affected area, and thus not be prompted to lick.
The condition so frustrated the profession that it was turning vets into modern-day carnival snake-oil salesmen. Some vets applied venom milked from the king cobra to numb the area and relieve pain. This was not obtained humanely from the snakes, and it did not succeed in curing the discomfort of the pets treated with it. Other vets tried “Substance P,” an extract of the pitcher plant with long-acting local anesthetic properties, which also failed to help.
These approaches assumed that, if only the lesion could be numbed, then the dog would stop its licking. And they were all unsuccessful because compulsive disorders have psychological, not physical, roots. I once encountered a dog who had no sensation in his foreleg as a result of being hit by a car. Despite this lack of feeling, the dog continued to lick a granuloma lesion on the same foreleg, even though the nerve supply to that leg had been demolished. Local pain and discomfort do not cause compulsive licking. Bitter-lemon sprays, cone collars, snake venom aimed to treat the symptom, when we needed to find a way to treat the cause.
In the midst of our studies on stereotypies, Dr. Judith Rapoport, a child psychiatrist at the National Institutes of Health, published a book, The Boy Who Couldn’t Stop Washing, about childhood obsessive-compulsive disorder. When she returned to her office after her national book tour, she found a slew of messages saying, “My dog does that compulsive self-washing, too.” Some psychiatrists might have dismissed these messages out of hand, but Dr. Rapoport took them seriously. What if these dog owners were right?
An expert at designing mental health studies, Dr. Rapoport planned an experiment in which dogs with acral lick would be enrolled in clinical drug trials for three known anti-obsessional medications: Prozac, Zoloft, and clomipramine. She found that the dogs responded to human anti-obsessional medication just as human subjects did, and so Dr. Rapoport concluded that dogs could indeed suffer from a canine form of OCD. In addition, and just as importantly, their compulsion responded to the same medications that help human sufferers.
Following Dr. Rapoport’s initial publication on canine OCD in the Archives of General Psychiatry in 1992, stereotypies were reclassified as compulsive disorders in veterinary medicine. Her publication was a game changer for all of us vets interested in repetitive behavior disorders. Vets now had a new understanding of what was going on and could develop more logical and successful ways of treating these conditions. These behaviors weren’t simply mindless and pointless after all, but were an animal’s way of dealing with underlying anxiety and stress.
Dr. Rapoport’s insights led me to take what I call an ethological approach to understanding compulsive behaviors in all animals. Ethology refers to the behaviors of animals while in the wild. Ethology might be a somewhat confusing term, lost, as it can be, among the welter of “ethnology,” “etiology,” and the myriad other “-ology” words. But it is a simple concept to grasp. When looking at pet behavior, we recognize the natural conditions that influence how the animals act, and we consider the evolutionary processes that might have led to their adaptive traits.
With Poker’s Queen Bee and Mobey, for instance, their cribbing was a response to being denied their natural activity of free-range grazing. Confinement prevented a normal activity (grazing), which led to an abnormal activity (cribbing). Ethology provides a link between a creature’s natural and unnatural behavior.
Dogs are by nature a predatory species. Hunting is how their ancient untamed canine ancestors stayed alive. Hunting has two basic components, the chase and the meal. The two phases of canine predatory behavior are the “appetitive” phase, in which dogs search for, track, and home in on prey—and includes delivering the final killing coup de grace. What follows is the “consummatory” phase. After that, the behavior resets, and the phases repeat.
A common version of canine compulsive disorder involves visually focusing on and chasing elusive prey, whether lights, shadows, objects, insects real or otherwise, or even the dog’s own tail. This is the appetitive phase gone wrong. One owner of an English sheepdog described her dog’s behavior as “chasing imaginary rabbits around the kitchen until they disappeared down imaginary rabbit holes.” A German shepherd I knew of spent a good deal of her day snapping at imaginary flies. The behavior had started with real flies but continued in their absence.
I once encountered a junkyard dog who spent his days looking for something that wasn’t there. Amid his vast territory of trashed-out automobiles, the junkyard dog would search and search without ever coming up with anything. It was nonstop and pitiful. This dog was displaying appetitive behavior gone awry, a naturally occurring activity with the brakes off. His behavior recalled the old Hughes Mearns poem:
Yesterday, upon the stair,
I met a man who wasn’t there.
He wasn’t there again today
I wish, I wish he’d go away . . .
In these out-of-control appetitive behaviors, what once was natural becomes unnatural.
Consummatory phase compulsions in dogs include flank and blanket sucking. Dobermans, in particular, are at risk for this condition. Dobermans in the grips of this condition can suck their flanks raw. The ingestion of inedible objects can be another expression of consummatory behavior gone awry. Rock chewing, perhaps more annoying to owners than hurtful to dogs, is one example. Normally the affected pooches don’t swallow the rocks, but the habit can wear down teeth. In the rare instances where the objects are ingested, they can cause intestinal blockage, a potentially dangerous situation.
Dogs are also a grooming species. Grooming is necessary for a dog in the wild, because it helps remove traces of the last meal. Even a slight scent of decomposing food could be a giveaway when hunting upwind of some flighty prey. In addition, grooming helps keep a dog’s fur in tip-top condition. A dog that did not self-groom would be more likely to succumb to infections. Evolution selected out careful groomers for survival. But as we’ve seen, overgrooming leads to acral licking, the prototypical canine compulsion.
Other survival-linked behaviors include digging, an activity that is quite useful in the wild and harmless in pets—until it goes off the rails and becomes compulsive. Swimming is obviously natural, especially in water breeds, such as Chesapeake Bay retrievers, Newfoundlands, and Portuguese fishing dogs—President Obama’s favorite breed. But obsessive swimming, which can occur in these breeds, can lead to exhaustion and disruption of the so-called human-animal bond.
Lief, a young German shepherd, was driven to distraction chasing his own tail. I’m not talking about a few desultory backward lunges from time to time. I’m talking about frenetic spinning in tight circles for hours on end. Lief was totally fixated on his tail. And he was becoming gaunt from his continuous, frantic spinning and barking.
Anxiety appeared to be at the root of his problem. Hypervigilant by day and by night, Lief would whine and chase his tail at the slightest provocation. A common trigger was the sound of passing cars at night as well as their headlights making fast-moving shadows on the ceiling. Some anxious German shepherds will bite and bloody their own tails, to the point that the tails have to be amputated. Lief’s problem was close to being that severe. He had become so anxious that he barely ever made eye contact with his devoted owner. His behavior was not in any way natural or functional. It was pointless, repetitive, and verging on self-mutilation.
Attempting to retrain Lief so that he did not chase his tail would not have made any difference. He had a psychological problem, not merely a behavioral one. His tail chasing was likely the misdirection of pent-up, predatory urges. I diagnosed him with canine compulsive disorder.
But tail chasing in German shepherds is sometimes complicated by a localized kind of canine epilepsy. In people, OCD has long been linked with epilepsy.
We were able to control Lief’s problem using an anti-obsessional medication. Once he calmed down somewhat, we adjusted his lifestyle and ensured that his owner changed his own behavior in order to create a more entertaining environment for Lief, which would make him less anxious. He gave the dog more exercise, more attention, and more fun activities. We also added an anticonvulsant to the medication regimen, to address the suspected underlying seizure activity. Lief improved—“a night-and-day difference,” according to his owner. He lived to a good old age and died with a healthy, well-furred tail still attached to his body.
Whether tail chasing in German shepherds is a purely compulsive behavior or is driven by underlying seizure-like activity in the brain remains unclear. In fact, it’s a bit of a chicken-and-egg problem: Does the compulsion cause seizure-like activity, or do partial seizures, localized to a particular region of the brain, sometimes manifest as compulsive behavior? But at least we now have a better handle on managing compulsive behaviors in animals.
Cats also display compulsive traits. Two common feeding-related compulsions in cats are wool sucking and pica, which involve sucking on or eating nonnutritive substances. Wool sucking is similar to the blanket-sucking problem of Dobermans and may be akin to thumb sucking in children. These all represent displaced suckling behaviors. Affected cats will typically target woolen materials, plastic shower curtains, shoelaces, and the like. The behavior can wreak havoc on an owner’s belongings, and it is dangerous for the cat, who may wind up with an intestinal obstruction.
Besides cribbing, which has its roots in a pressing need to constantly chomp on something, horses can develop other compulsions related to their free-ranging impulses. They may pace, stall-walk, or fence-walk. Weaving represents an abbreviated form of walking to and fro, in which the horse swings his head from side to side as he walks in place.
Zoo animals exhibit compulsions that are typical to their species. Elephants who roam large distances in the wild will weave when tethered by leg chains. They might walk in place while swinging their heads from side to side. Giraffes do the same. Captive bears pace aimlessly in their cages. Big cats can wear out pathways around the periphery of their enclosure as they stride away their captive lives.
Over the years, I have consulted with zoos about numerous strange animal behaviors, including compulsive pacing behavior in polar bears. In nature, polar bears roam for miles in search of food on the ice shelves. When constrained in the zoo environment, mounting frustration at the monotony of their small environments can cause a polar bear to constantly pace to and fro along the same route.
At the Calgary Zoo, I helped placate a compulsively pacing polar bear named Snowball. The treatment was relatively simple. We gave Snowball Prozac. It worked so well that the zoo staff aired the results proudly in a letter to the AVMA journal.
Gus, a popular polar bear in New York City’s Central Park Zoo, like Snowball, exhibited compulsive behavior by a repetitive daily swimming schedule. Visitors to the zoo became upset witnessing Gus’s unerring to and fro. News reports made the “bipolar polar bear” into something of a cause célèbre. Zookeepers treated Gus with Prozac, too, although I was not the one to prescribe it. Additionally, his keepers worked to provide him with distractions. They scattered beach balls and other toys around his tightly limited environment—which was, as the press delighted in pointing out, the size of an average New York studio apartment. Gus’s repetitive behavior diminished. He died in 2013 at the ripe old age of twenty-seven.
Nearer to my home, at the Franklin Park Zoo in Boston, I came across an unusual OCD-like condition in a gorilla. The vets there described their charge as bulimic. He would eat a hearty meal and then promptly throw it back up. All medical causes of vomiting had been ruled out. But the gorilla was described as anxious, bordering on neurotic, a description used not just by tabloid journalists but by professional primatologists.
Bulimia is thought to be a condition in the obsessive-compulsive spectrum of diseases. The gorilla displayed an obsession that involved the feeling of being overly full after eating, followed by a subsequent compulsion to purge. I recommended treatment with an anti-obsessional drug, clomipramine, and an antianxiety drug, Valium. Some weeks later the gorilla had ceased vomiting and seemed more composed. His condition may have been simple anxiety/stress-related vomiting. It was tempting to place it somewhere along the OC spectrum, perhaps in a new category, the gorilla version of the disorder. GOCD?
In the wild, birds are natural preeners. When stressed by confinement, birds overgroom and pluck out their feathers. Alex, the celebrated African gray parrot trained by the psychologist Irene Pepperberg, was a confirmed feather plucker. Recognized as an Einstein among birds, Alex led something of a high-pressure existence. Between intense training sessions by Irene or her students, Alex had to endure long hours in his cage. Effectively in school every day, he was caged when not being taught to recognize objects, understand concepts, and communicate. Irene also traveled a lot, doing presentations about her prize pupil’s accomplishments.
Alex’s life was unnatural for a parrot. It’s not hard to see why Alex displaced his frustrations as feather plucking, which then became ingrained as a true compulsion. Even Einstein might have become a bit of a nutty professor in response to such limiting conditions. Alex died prematurely from arteriosclerosis, or hardening of the arteries, a condition which in humans is often exacerbated by stress.
Feather-plucking parrots perform a set of ritualized actions that would be fascinating if they weren’t so painful to watch. The birds search for new-growth feathers, pull them out by roots with their beaks, transfer them to their claws, and inspect them carefully. They then shred the feather shaft, creating a miniature fan appearance, before discarding it and starting the whole sequence over again.
This behavior is similar to the human disorder, trichotillomania, a compulsive need to pull out one’s own hair. Trichotillomaniacs sometimes chew on, or even eat their own hair, a condition called trichophagia. People with trichotillomania often search for new-growth hairs, pluck them out, and inspect them. They might chew the hair bulb. They then discard the hair. The behavior repeats ad infinitum, or in some cases, ad nauseam. The two conditions, occurring in parrots and people, are uncannily similar.
Cats are also “obligate groomers,” an easy term to remember if you consider their inveterate need to self-groom. Such natural behavior can develop into an overgrooming compulsion called psychogenic alopecia, which is basically a feline form of trichotillomania. Highly strung, anxious, genetically susceptible cats are particularly prone to developing the disorder when the pressures of feline life become too much to tolerate.
One such cat I encountered began overgrooming while her surgeon-owner was away for five weeks at an international conference. When the owner finally returned home, she found her living room covered with what looked like snow, but was her cat’s white fur, pulled out in clumps. Oddly, the cat had begun to bite its nails during her absence, too. The surgeon, feeling guilty that her overseas trip had caused such distress to her beloved animal, brought the pet in to see me. The cat’s normal grooming pattern had been exacerbated by stress. I treated the cat with an anti-obsessional medication designed to stabilize its mood. I’m happy to report that it recovered beautifully. The surgeon was grateful. I’m sure the cat was mightily relieved, too.
Another cat—a cute-looking calico called Kalie—developed psychogenic alopecia when her kindly owner, the late Dr. Bob Fleishman, principal of a local veterinary clinic, brought home another cat that had been dropped off at his practice. But here’s the rub: cats do not automatically appreciate new acquaintances, let alone permanent housemates, and the arrival of the new cat—well, put the cat among the pigeons (so to speak). Neither do we appreciate everyone we meet, come to think of it. If I was to take someone off the street and drop them off in your home, your reaction would not be, “Oh good, just what I wanted—a fellow human. A person with whom to share my house, bathroom, and dining room.” Poor Kalie hid as soon as she clapped eyes on the newcomer; in fact, from that day forth she became a recluse—and started to overgroom and strip her fur out all along her underside and inside her fore- and hind legs. Bob consulted me and asked what he could do. At that time, I was big on the opioid antagonists, so I prescribed one of these medications to be administered once daily by mouth. The good news: it worked! The bad news: the medication was so bitter to taste that Bob could not catch the cat to medicate it after a month or so. It seems the bad taste was worse to the cat than its nemesis, so Bob eventually quit giving it. Poor Kalie had to live out her days privately and somewhat hairless underneath.
Psychogenic alopecia in cats, acral lick dermatitis in dogs, feather plucking in birds, and trichotillomania in people are basically all forms of compulsive overgrooming—this constant repetition of survival-necessary behaviors is thought to be caused by anxiety. Anxiety leads to a “loosening of the brakes” on natural behaviors so that they run amok.
Animals that exhibit compulsive behavior are generally more anxious than their normal, non-compulsive counterparts. To invoke a popular psychological concept, they seem to be worriers with type A personalities. Back when I first began working with anxious, obsessive-compulsive animals, the DSM of mental disorders did not place OCD among anxiety-linked conditions. But the sorting of mental disorders is an ongoing endeavor. A subsequent version of the DSM—“Version IV (Revised)”—changed the classification, grouping OCD with other anxiety-type disorders. OCD was moved again in Version V, and now has a category all its own. I’d argue that this might not be the best placement, given that many people with OCD often do seem to be worrywarts, so the link to anxiety should have been maintained. In my experience, animals with equivalent disorders certainly display increased anxiety.
Anxiety triggers an over-the-top release of survival-necessary behaviors in what develops into an unvarying cycle. Here’s how I believe it works: Worry, or indecisive signaling from the decision-making region in the brain, activates nervous pathways “downstream.” The performance of a particular behavior pattern lessens the anxiety. In other words, the compulsion serves to relieve the anxiety. But this relief is only temporary. In people with OCD, it’s not long before the anxiety and drive to perform the compulsion return. The cycle continues.
No animal in the wild has ever been found to engage in a compulsive behavior. I doubt that humans living in a natural environment, fending for themselves and beset with real worries—let’s say, for example, the Korowai tribe in deepest Papua New Guinea—exhibit OCD, either. Cannibalism, yes. Compulsive hand washing, no.
I conducted research in a psychiatric clinic that treated people with trichotillomania, seeking to ascertain when their conditions first started, if they’d ever had any remission, and if they were aware of any triggers. The first patient I spoke with was a man who was a habitual beard plucker (a form of “trich”). The condition had abated once, he told me, for a few weeks when he was hitchhiking across Canada.
This makes sense. On the trip, the beard plucker was looking out for himself, trying to stay safe, sleeping under the stars, making fires, battling the elements, and wondering whence his next meal would come. There was no time to obsess about plucking out his beard as he lived a genuinely natural hominid lifestyle. The behavior resumed as soon as he got home. It took over in force once more in front of a flickering computer screen at his place of work.
The second patient I quizzed was a woman who was a compulsive eyebrow plucker, another form of trich. She had started this odd behavior right after she got married. Her behavior had abated once when she took a cruise without her husband, a round-trip from Boston to the Caribbean. But it had resumed on the way home, four miles out of Boston harbor. Couples therapy might cure her compulsion, but I didn’t feel it was my place to make that recommendation.
Animal compulsions that are triggered by stressful events or thwarted natural inclinations may sometimes be relieved by changes in environment. Most compulsions initially arise around puberty or in early adult life, always a stressful time for animals and people alike. For example, around 80 percent of blanket-sucking Doberman pinschers engage in this compulsion for the first time before they are one year old. Sexual maturity in such dogs occurs at around six to eight months, while they are technically still in late puppyhood. Think of adolescent teenagers, and consider their stresses at this stage of life.
Caged mice can exhibit compulsive behaviors, too, though the behaviors they show—jumping, climbing, sniffing, and rearing—are more often referred to as stereotypies. These behaviors can be induced by stimulants and blocked by treating them with an opioid antagonist, such as naloxone. In one experiment, researchers gave compulsively jumping mice two different forms of the drug. One form of the drug was active—effective in blocking the effects morphine and internal morphine-like substances, the endorphins. The other similar drug, because of its mirror-image structure, was supposedly ineffective as a morphine or endorphin blocker and so was used as a control. But to the researchers’ surprise, both drugs stopped the compulsive jumping behavior. What on earth was going on? What should have happened, according to our work with Mobey, is that the form binding to opioid receptors would stop the mice from jumping. The other would not.
When Lou Shuster and I looked into this experiment, we discovered that the supposedly inert form of the drug actually did accomplish something. It blocked a set of brain receptors called NMDA receptors and limited the effect of a neurotransmitter called glutamate, which stimulates nerve cells.
Suddenly Lou and I found ourselves playing in a whole new ball game. We were forced to take a new look at our old work. Given what was happening to the mice, the fact that the cribbing horses stopped cribbing could have been due to blocking so-called NMDA receptors for glutamate and for endorphins.
To put our new theory to the test, we obtained various glutamate blockers, some with and some without the reverse opioid structure. We gave one of our horse subjects a very small dose of ketamine, which acts as an anesthetic when used in sufficient quantities. Lou and I settled on ketamine because it, too, is a powerful NMDA blocker. It’s also well-known and deadly as a street drug of choice, under the slang name of Special K. One Medicine, indeed.
The first horse to whom we gave ketamine was a champion cribber, just like Poker’s Queen Bee had been. When we monitored her before giving her the drug, she chomped at the wooden stall door almost incessantly. She seemed unaware of her environment or us lab-coated observers. After we injected her with a tiny dose of ketamine, the mare reacted with a momentary startle, as if she had just thrown back a double shot of Scotch. Then she relaxed, stopped cribbing completely, and began to show interest in her surroundings.
The drug’s effects lasted for around twenty minutes. I offered her a ripe apple that time and she readily took it. Highly palatable foods such as sweet-feed grain and apples can trigger bouts of cribbing in horses, so this was really putting the treatment to the test. But she didn’t crib at all. She was just a happy horse munching on a Granny Smith.
To replicate our success, we tried out another, more readily available glutamate-blocking drug, dextromethorphan, on several other cribbing horses, who once again stopped their compulsive behavior. An active ingredient in many cough suppressants, dextromethorphan is known to be safe. We found similar results in dogs who had been self-licking, self-chewing, and self-scratching. We also found that mice with induced compulsive scratching stopped doing it when given NMDA-blocking drugs.
It was a short leap from these findings to concluding that an NMDA blocker might work as a treatment for people with OCD. Realizing the possible value of this discovery, Tufts University took out a patent for the use of NMDA receptor blockers in treatment of compulsive disorders in animals and people.
The patent application extended the human application to the “compulsive components” of tobacco smoking and drinking. Smokers and problem drinkers in remission tend to fight their habit for their entire lives, long after the physical addiction to the chemical has faded away. That resembles a form of OCD. The obsession takes the form of daily thoughts about cigarettes or alcohol, while the compulsion is the act of imbibing an alcoholic drink or lighting up a cigarette.
The compulsion can be checked with determination and help from support groups, including retraining that substitutes healthy habits for the unhealthy ones. But the obsessive, constantly recurring thought is difficult to suppress. That is why alcoholics in recovery take things “one day at a time” and former cigarette smokers know that even one cigarette might lead them back to their addiction.
We thought that our approach could help quash the compulsion and make recovery from alcohol addiction or smoking easier. Many of the medical treatments currently available do have NMDA receptor-blocking properties and, although the medications are not always billed as working through this mechanism, we believe it to be instrumental in treating these addictions, at least in part by blocking associated obsessive-compulsive components. Pharmaceutical companies, normally eager to exploit every opportunity, did not recognize that aspect of the drugs and therefore paid no attention to our patent. There is still no approved NMDA blocking drug for treatment of animals or people with compulsive disorders despite an estimated $350 to $500 million market.
Dr. Shuster and I needed to find a way to prove that NMDA blockers work for the treatment of OCD in humans. A Harvard psychiatrist colleague, Dr. Michael Jenike, was interested in our idea, agreed to try the NMDA blocker dextromethorphan in some of his most intractable OCD patients, and noted some modest decreases in anxiety for some patients. We then persuaded him to try a more reliable NMDA blocker, memantine, marketed for treatment of Alzheimer’s disease in humans under the trade name Namenda. Namenda reduced the OCD behaviors so well that Dr. Jenike still uses Namenda off-label today with many tough-to-treat OCD patients.
When we tried Namenda in dogs with a variety of compulsive disorders, it worked very well. One particular Cavalier King Charles spaniel had demonstrated almost nonstop chasing behavior, fixating on a variety of objects, one after another. His normal canine appetitive activity had gone out of control and he indulged in his compulsion to the exclusion of a normal life. He had virtually no relationship with his owners. If there was nothing else to chase, the dog would throw himself at armchairs to make the dust fly out so he could then chase the particles as they danced in rays of sunlight.
Prozac slowed down this dog, but only the addition of Namenda made the troubling behavior cease.
Not only did our theory prove to be a workable solution for people with OCD, but its discovery highlighted something important about One Medicine. Most often, drugs are developed within Big Pharma companies, tested in rodents, and then undergo human clinical trials until they can be marketed for human use under a brand name. Usually, veterinarians then pick up on the idea and try the same drugs in their patients, often with equivalent success. The pharmacological arrow, in fact, almost always points that way.
There are some notable exceptions to this “humans first, animals later” pathway of medical applications. One is the well-known glucosamine-chondroitin combination, which was originally developed for joint repair and relief of joint pain in racehorses, then found its way into human sports medicine.
Our NMDA treatment also reversed the usual order of things. We had developed the NMDA-blocking treatment of compulsive disorder in pet animals first. That treatment then headed for human psychiatric use. We had “reversed the arrow”—using what we’d learned about animals to develop an effective treatment for humans.
While Dr. Jenike still uses off-label Namenda to help hundreds of OCD sufferers, the med is something of an orphan treatment for OCD. The patent we developed at Tufts was never taken up by a major pharmaceutical company. In June 2013, another medical research team discovered that the NMDA blocker, ketamine, was an effective treatment for OCD in people—exactly the same finding in our cribbing horse many years ago. Even though it is not yet used widely, it continues to show promise for treating OCD and various psychiatric disorders. We also discovered in the 1980s, that opioid antagonists caused penile relaxation in male horses and that they led to almost instantaneous evacuation of a horse’s bowels. If we had capitalized on any of these discoveries, we could have hit the jackpot with the first Viagra-type drug and a drug to treat constipation. Now, some thirty years later, these treatments have become a reality.
Oh, well. Maybe in my next life I’ll be a businessman!
I have long believed that OCD is fundamentally a single disorder that simply differs from species to species in the way it’s expressed. To look deeper into animal compulsions, I needed to examine the genetics of affected animals, and perhaps also the structural changes in their brains. I believed that anything we found would help establish similarities between compulsive behaviors in animals and human OCD that could eventually shed more light on the human condition.
I contacted Dr. Edward Ginns, a pediatric neurologist and geneticist by trade and a former NIH branch chief. Ed had been hired by UMass to head up the Brudnick Neuropsychiatric Research Institute and is an expert at looking at the genetics of closed populations, such as the Amish demographic in Pennsylvania Dutch country. Pedigree dog breeds are, by definition, closed populations. We planned a study of certain compulsive behavior prone breeds, using the same approach that Ed had employed with human populations. We decided to study flank-sucking Doberman pinschers, tail-chasing bull terriers, cribbing horses, and two separate breeds of wool-sucking cats, Siamese and Birman.
We began by creating a DNA bank from affected and control animals to store for later analysis. I collected samples from dogs, cats, and horses, all of whom exhibited various animal compulsions. As scientists, we always require a control group for comparison, so I also took samples from animals who were not affected. We recorded detailed information about various symptoms the animals were showing, how serious the problem was, and what other problems they suffered from.
We chose to analyze dog DNA samples first because the canine genetic test was the only one then available—full genome maps of horses and cats were at that time still in development. And we processed the DNA from Dobermans first because the breed’s compulsive behavior was manifest in the purest way. Flank sucking in the breed was clearly genetic, with up to 70 percent of some litters being affected. It can also be harmful to the dog, causing severe physical problems including lip calluses, buckteeth, and gastrointestinal issues, as well as intestinal obstructions that can be fatal. We held off analyzing the bull terriers, since that breed had seizure issues and a zinc deficiency problem—in addition to what appeared to be compulsive behavior—which could have clouded our conclusions.
In addition to flank-sucking behavior in Dobermans, we also observed that the affected dogs had a great penchant for collecting and sometimes arranging objects, a behavior Dobie owners called “shopping.” One rescued Doberman was caught on camera arranging his collection of Beanie Baby toys in symmetrical patterns. On one day he would organize them in triangular patterns, the next in straight lines or cruciate designs. Most often the Beanie Babies were all the same type, all stuffed bears, for example. The Dobie usually laid each of his dolls facing the same way, up or down.
After his rescue and placement in his new home, it took this dog several weeks before he felt comfortable enough to allow his owner to give him a hug for the first time. The very next day, the Beanie Babies were arranged in pairs, one facing up and another above facing down as if they, too, were hugging.
After the painstaking process of collecting the DNA samples from the Dobermans, it came time to analyze them to see what was really underlying this clearly compulsive behavior. The results were exciting. We found an obvious glitch on chromosome 7, a clear discrepancy between affected and normal dogs. That particular region of the chromosome contained only one huge gene, known as neural cadherin, or CDH2.
The cadherin family of genes as a whole is interesting. Cadherins are implicated in numerous developmental disorders. This particular gene is expressed in the brain and is necessary for the proper formation of synapses, or the gaps between nerve cells. The nerve cells transmit chemical messages across these synapses, forming a chain of connection along which our thoughts travel, our internal organs are instructed and our actions are initiated. CDH2 is also responsible for the proper formation of NMDA receptors.
It all fit together. We were zeroing in on several factors that disrupted the natural flow of communication in the brain. This occurs on a cellular and even a molecular level. As with our former studies in PTSD research, we were going in deep. A series of minuscule neural miscues seemed to trigger the set of repetitive thoughts and behaviors that could be instrumental in driving OCD.
We took our findings to the National Institute of Mental Health (NIMH), whose scientists were intrigued. They agreed to look at CDH2 in DNA samples from people with OCD, investigating if the same brain glitch we found in Dobermans could be involved in causing OCD in humans. Regions of the CDH2 gene in people with OCD were found to be associated with an extreme form of OCD and provided genetic evidence of a known link between OCD and Tourette’s syndrome. More recently, a South African study has shown that variations within the CDH2 gene are definitively associated with OCD in people.
Ed and I continued to work with our compulsive Dobermans, and joined forces with a canine geneticist, Dr. Mark Neff, of the Van Andel Institute in Michigan, to reanalyze our Doberman DNA samples. This time we used a more advanced genetic tool to flag other suspicious chromosomes.
Comparing seriously affected dogs with mildly affected ones, we made another exciting discovery. We found a region of great interest on chromosome 34, an area on the genetic chain that contained serotonin receptor genes. Recall that OCD responds to treatment with serotonin-enhancing drugs, such as Prozac. At one time, OCD was thought to be a serotonin-deficiency syndrome. Modifying serotonin levels in the brain is still the primary treatment strategy. Dr. Ginns and I reasoned that the anomaly on the CDH2 gene needed to be present for a dog to be susceptible to their compulsion. The severity of the disorder, however, was determined by the serotonin gene anomaly on chromosome 34.
My veterinary behavior resident at the time, Dr. Niwako Ogata, wondered if we could take a completely different approach to finding parallels between compulsive behavior in Dobermans and OCD in humans. She came up with the idea of looking at the detailed brain structure of affected Dobermans using voxel-based morphometry (VBM), a sophisticated version of magnetic resonance imaging (MRI).
The results yielded another eureka moment. The brains of affected Dobermans had structural differences very similar to those identified in humans with OCD, hoarders in particular. That revelation is particularly interesting, given that Dobermans are hoarders, too.
Our OCD work has had wide-ranging practical application. If you know the cause of something, it becomes a lot easier to develop logical solutions. For example, CDH2 interacts with proteins called catenins within the cells. The word catenin comes from the Latin catena, meaning “chain,” and that’s what we are looking at now, a chain or pathway activated by CDH2. We know that CDH2-catenin complex is involved in learning and memory and believe it is involved in propagating OCD. It is no surprise to us that a catenin antagonist has recently been shown to help recovering alcoholics overcome their compulsion to drink. Fixes of this type take the kind of information we are seeking and finding, and though such research to address the mechanisms involves a whole lot of trial and error, the results, when they come, are well worth waiting for.
Ozzy the Oddball was a ten-month-old, 22-pound castrated male schnoodle, a schnauzer-poodle mix with a hangdog look on his large, pretty face. Sadly, ever since he was six months old Ozzy exhibited a number of odd behaviors. He would “stargaze,” disconcertingly staring off into space at nothing, or engage in “fly snapping,” trying to catch imaginary flies with his teeth. When not busy with those endeavors, he might obsessively lick either himself or various objects around the house. When we saw Ozzy at the clinic, he showed clear signs of compulsive behavior, perhaps complicated by a type of partial seizure.
With every animal we treat, we try to address issues with both pet and owner. Owners play a key role in helping their animal get better. We need the partnership of owners in administering medications, and helping with behavior modification. For Ozzy, we recommended that the owner withdraw attention when Ozzy engaged in his abnormal behaviors. That way, Ozzy would not be rewarded for behaviors the owner didn’t want.
Ozzy also needed aerobic exercise, a regimen reinforced by a consistent daily schedule and a more interesting home environment. On the pharmacological side, we prescribed Namenda, our reliable NMDA blocker. Over the next few weeks, the owner rated Ozzy as 50–75 percent better.
But animals, just like human beings, are subject to accidents and reversals. After he started his therapy, Ozzy had a taxing experience in Florida. He became too frightened to cross a boardwalk. Soon afterward, his owners had to board him in a kennel for a time. The resulting stress, combined with a switch to a cheaper drug, dextromethorphan, led to a full-force return of his strange behaviors. He resumed stargazing at near full intensity and began obsessively rubbing his eyes and licking his paws.
What more could we do? We had seemed to help Ozzy briefly with his compulsions, but now we were almost back to square one. It would turn out that Ozzy and dogs like him were suffering from partial seizure activity expressing itself in the form of OCD-like signs. The link between partial seizures and compulsive behavior was a revelation first suggested to me by my earlier bull terrier work and later confirmed by dogs like Ozzy. It is unclear why OCD tends to occur with epilepsy—both in people and animals—and we’ll explore that link further in the next chapter.