Recognition, Management and Genetic Findings in Canine and Feline Obsessive Compulsive Disorders
Nicholas H. Dodman, BVMS, DACVA, DACVB
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA
In humans, obsessions are constantly recurring thoughts which intrude into a person's mind and cause anxiety unless acted upon. Compulsions are those actions that result from the obsession, and the act of performing them brings temporary relief. Unfortunately, the obsessions all too frequently reappear, and the cycle is propagated. A diagrammatic representation of this obsessive-compulsive disorder (OCD) cycle may be found on the website www.ocdhelp.org/ocdfacts.html (VIN editor: The webpage was unavailable as of 9/1/15). The discovery that dogs may suffer from an equivalent condition was first pointed out by Goldberger & Rappaport (1991) and Rappaport et al. (1992). Their studies focused on the canine compulsion known as "canine acral lick," which they regarded as having face validity and predictive validity as an animal model of obsessive-compulsive disorder (compulsive handwashing) in humans. Specifically, they noted similar development and expression and found an almost identical response of affected dogs to medications used to treat human OCD. Compulsive disorders are now well recognized in the veterinary community as having multiple expressions and affecting many species, though there is reluctance to apply a prefix "obsessive" because animal obsessions are impossible to prove.
Canine Compulsive Disorder
Between 2–5% of dogs seen by veterinary behaviorists are diagnosed with canine compulsive disorder (CCD). In comparison, between 1–3% of the human population suffers from what could be termed "classical" OCDs. Factors involved in the development of CCD are analogous to those involved in the development of OCD, specifically a) that there appear to be genetic underpinnings (breed and familial), b) affected individuals tend to have an anxious personality, c) seem to be responding to environmental stress, d) may start with a displacement behavior in response to stress, e) the behavior becomes fixed and displayed in the absence of the original stressor. Ethologically speaking, compulsive disorders in animals and humans derive from normal species-typical, hard-wired behavior patterns that are necessary for survival. In dogs, these include grooming, predatory behavior, ingestion, and locomotion. Humans, as a hunter/gatherer species, tend to develop compulsions derived from concerns for personal safety and the gathering or collecting of things, including sometimes the collection of animals. Acral lick in dogs derives from grooming, while compulsive tail-chasing, light/shadow chasing and fly snapping appear to derive from predatory roots. Flank or blanket sucking is an ingestive compulsion, while running in geometric patterns is a compulsion stemming from a hard-wired locomotor behavior.
Specific Canine Compulsions
Acral Lick Dermatitis (ALD)
This compulsion involves overgrooming of the lower extremities of the four or hind legs, resulting in excoriation and deep ulcer formation. Granulation tissue formation ("lick granuloma") and secondary infection are sequels. Acral lick dermatitis is often confused with medical conditions - and there are a few medical conditions that have a similar appearance and must be ruled out, but true ALD is primarily a mental condition, not a physical one. Acral lick dermatitis is most common in large, active breeds of dog, such as Dobermans, Labradors and Golden Retrievers, Great Danes, and German Shepherds. The condition appears to have a significant genetic component.
Flank Sucking & Blanket Sucking
This condition involves repetitive mouthing and sucking of the flank region of the dog or sucking on and sometimes ingesting parts of blankets. It appears to derive from suckling behavior of the young dog and thus falls into the category of an ingestive compulsion. It is most common in Dobermans and in this breed, up to 70% of a single litter can be affected. Dachshunds and Weimaraners, two other German breeds, are sometimes affected, suggesting that the mutation responsible for conferring susceptibility to this condition originally occurred in this region of Europe. Although Doberman owners often regard this compulsion as benign, physical injuries can result, including oral issues and intestinal obstruction from ingested material (Moon-Fanelli et al. 2007). Ogata et al. (2013) showed that brain structural abnormalities in Dobermans were closely similar to those in human OCD, including higher total brain and gray matter volumes and lower dorsal anterior cingulate cortex and right anterior insular gray matter densities found on MRI. Affected dogs also had higher fractional and isotropy in the splenium of the corpus callosum, the degree of which correlated with the severity of the behavior phenotype. A genome-wide association study (GWAS) of 92 affected and 68 control Dobermans found a highly significant association of a locus on CFA 7 in the affected dogs (Dodman et al. 2010). That region contains only one large gene - neural cadherin (CDH2) which expresses itself in the brain (hippocampus and cerebellum) and is responsible for proper synaptic development and the formation of NMDA receptors (receptors for the excitatory neurotransmitter glutamate).
This compulsion, which presents as dogs spinning in circles and chasing their tails, presumably derives from hard-wired predatory behavior. Dogs may vocalize and injure themselves in the process of tail chasing if they catch and bite their tail. Bull Terriers and German Shepherds - and their crosses - appear to be particularly susceptible to this troubling condition. In a large study of compulsive tail-chasing Bull Terriers, the tail chasing phenotype was associated with concurrent trance-like behavior, presumed partial seizures, aggression, and phobias (Moon-Fanelli et al. 2011). In addition, males were at a significantly greater risk of developing this condition. Post-hoc analysis of a subset of these dogs showed that affected dogs were significantly more withdrawn around people and were significantly more preoccupied with objects (data on file, Tufts University 2014). All things considered, these significant findings pointed toward a canine form of autism rather than CCD, with the tail chasing itself merely a type of motor-tick or stereotypy resulting from the underlying condition (Children with autism are also known to spin in circles). To support our contention, we looked at biomarkers, neurotensin and corticotropin-releasing hormone (CRH), and found that serum levels were elevated in affected dogs, as they are known to be in autistic children (Tsilioni et al. 2014). A genome-wide association study of affected versus control dogs showed peaks on Chromosome 4 and the X chromosome (10-5 and 10-6, respectively). These findings are evocative but require to be investigated more thoroughly. To this end we are poised to conduct whole genome sequencing in six severely affected Bull Terriers versus a previously sequenced control and/or a large database of non-tail chasing dogs and hope to have results within 6 months. It has always been my contention that the Bull Terrier tail-chasing syndrome is more neurological than compulsive, and our own unpublished results as well as the published work of Dr. Hannes Lohi in Helsinki, Finland, has shown that the CDH2 gene is not involved in the Bull Terrier tail-chasing syndrome. But Lohi, like us, did also find a statistically significant locus on CFA 4 in tail-chasing Bull Terriers.
German Shepherds, on the other hand, though affected dogs also chase their tails, do not show any of the signs of autism that we see in the Bull Terriers. We have a large number of German Shepherd samples awaiting GWAS but have yet to begin that study. We would hope to confirm CDH2 involvement in this breed. DNA from a similar breed, the Belgian Malinois (Belgian herding dog), which express a different locomotor compulsion of circling, has indicated that CDH2 gene is associated with their behavioral compulsion (Cao et al. 2015). It was suggested by these authors that selecting Belgian Malinois for optimal work performance predisposed them to the circling compulsion as circling dogs performed better at when "at work." Note the European origin of these sheep herding dogs, even though the compulsion expressed is different from that of the Dobermans.
The behavior manifested by dogs with this compulsion is self-explanatory. Breeds affected include Border Collies, Old English Sheepdogs, Rottweilers, and Wire-Haired Fox Terriers, all breeds with high prey drive. Although this compulsion tends not to result in serious injuries, it is nevertheless distressing for owners and has sometimes led to the surrender of affected dogs. We have collected hundreds of samples of DNA from light- and shadow-chasing Border Collies and controls. Again, these samples are awaiting analysis.
Dogs affected with this condition snap in the air as if biting at flies, though there are none there. It affects mainly Cavalier King Charles Spaniels, Bernese Mountain Dogs, Miniature Schnauzers, Norfolk and Norwich Terriers, Springer Spaniels, Labrador Retrievers, and German Shepherds. If fly snapping is indeed a compulsive behavior, it is probably derived from predatory roots. However, there is some doubt as to the purity of this supposed CCD, as dogs with complex partial seizures also manifest an identical disorder. These latter dogs respond to treatment with anticonvulsants. Partial seizures can be a complicating factor in the diagnosis of many CCDs, as the expression of the various repetitive disorders can be overlapping. Some compulsive behaviors may have a partial seizure component and, in fact, it is known that 10–20% of humans with OCD have partial seizure involvement. We have attempted to differentiate seizure disorders from CCD in some cases by means of EEG and have shown that tail-chasing Bull Terriers, for example, manifest an abnormal epileptiform pattern (another strike against the condition being purely a CCD).
Treatment of CCD
Behavioral treatment of CCD involves identifying and addressing underlying stressors and tackling them as far as possible. We also advise no reinforcement or punishment of the behavior, establishment of a set daily routine, increased exercise, and environmental enrichment. That said, the majority of dogs will not improve with such treatment alone, and pharmacotherapy is often necessary - as it is in humans. Selective serotonin reuptake inhibitors, such as fluoxetine (Prozac), are the main stay of treatment, but other options include using NMDA antagonists, which block the neurotransmitter glutamate or, for reasons mentioned, adjunctive treatment with anticonvulsants.
Feline Compulsive Disorders
As with dogs, feline compulsions seem to derive from normal behaviors such as ingestion and grooming. They are, in effect, natural behaviors gone awry and seem to have both genetic and environmental factors underlying their expression. The two most common feline compulsive disorders are wool sucking and psychogenic alopecia. Feline hyperesthesia and hoarding are two less common feline OCD-like behaviors.
This behavior, which involves primarily Oriental breeds of cats, involves sucking and chewing on woolen and synthetic substrates. In that sense, it appears to be the feline equivalent of Doberman blanket sucking. Cats with the wool-sucking compulsion may progress to ingesting cloth, hair, plastic, shoelaces, electric cords, paper, and even wood. At this stage the condition is sometimes termed "pica." Wool sucking is detrimental to the cat because it can lead to health issues, notably intestinal obstruction; it is also a considerable nuisance and expense for the cat owner. The fact that Oriental breeds are primarily affected - with Siamese accounting for 50% of affected cats - suggest strongly that genetic features are involved. We have plotted genealogies of affected cats, and there seems to be a dominant mode of inheritance of this disorder, perhaps with incomplete penetrance. In collaboration with Drs. Leslie Lyons and Barbara Gandolfi and our genetic team at UMass, we conducted one genetic study (GWAS) of Siamese and Birman cats (100 of each, half affected, half controls) and came up with some intriguing findings that warrant further study. It was the Birman cohort that pointed the way. As it turns out, cats that owners described as Siamese were not genetically a uniform group (per MDS plot) and were thus not employed in the analysis. In the Birmans, we found two genes of great interest. The first, NCALD, is a gene that encodes for a member of the neuronal calcium sensor family of calcium-binding proteins. Most recently, calcium has been found to be intimately involved in the propagation of OCDs. A second gene, RRM2B, is a gene that encodes the small subunit of a P53-inducible ribonucleotide reductase. The gene itself is linked with depression, migraine, and learning difficulties, and so has central nervous functions. We would like to investigate these two genes further, and are on the cusp of doing that.
This condition is very similar to the human compulsion known as trichotillomania. Basically, it is a displaced grooming behavior that assumes compulsive proportions with the continuous stripping out of the cat's hair coat in a classical ventral pattern. It occurs primarily in cats with an anxious temperament and, in our experience, is always initiated by an acutely stressful experience. Once again, Oriental breeds are overrepresented, and like human OCD, it often arises in early adulthood and is most common in females. Genealogies seem to indicate a dominant mode of inheritance with incomplete penetrance.
There are people who regard feline hyperesthesia syndrome as a grooming compulsion, and certainly it can present that way. Also, it sometimes responds to classical antiobsessional drugs. However, of late, I believe that feline hyperesthesia is a condition resulting from complex partial seizure activity, as some cases progress to overt tonoclonic seizures and many respond well to anticonvulsant therapy. Like psychogenic alopecia, the onset of feline hyperesthesia is associated with an environmental stressor. It affects cats typically in the 2–6 year age range and seems to target Oriental breeds or their crosses. Feline hyperesthesia is another one of those conditions that seems to blur the distinction between a compulsion and a partial seizure.
Feline Compulsive Behavior Treatment
Treatment is along the same lines as it is for dogs, by addressing underlying stresses and enriching the environment. In addition, the same arsenal of drugs is helpful to treat feline compulsive disorder, including antidepressants and anticonvulsants.
Canine and feline compulsive disorders have many factors in common with human OCDs. Some have compelling similarities in terms of face validity (acral lick in dogs versus compulsive hand washing in people; psychogenic alopecia in cats and human trichotillomania). All have predictive validity in terms of their response to medications. More recently, elements of the full construct of homology, ranging from MRI and genetic findings in the Doberman have begun to surface. Two papers have been published about the CDH2 gene in humans with OCD. One found four novel SNPs, one of which was associated with a severe form of OCD and other psychiatric disorders in one patient, and the other seemed to link OCD and Tourette's syndrome. The second more recent paper reported polymorphisms within the neuronal cadherin gene associated with human OCD. Determining the genes involved in compulsive disorders in humans and animals will shed light on the neuronal pathways driving the behavior. This, in turn, opens avenues for new therapeutic interventions as well as permitting the development of tests for genetic susceptibility. For animals, tests for genetic susceptibility would be valuable to breeders and would be helpful for human doctors and patients alike.
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