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Years ago I was introduced to a white 1-year old neutered male bull terrier who was relentlessly chasing his tail. I had just read a case report of just such a dog published in the Journal of the American Veterinary Medical Association. In fact the dog referred to in the article was cookie cutter similar in all respects; same problem, same breed, same age, same color, same sex and neuter status.
This “coincidence” confirmed for me that the problem was genetic and started what became a 30 year study of this problem in the breed. To start with we all thought the problem was a stereotypy – a pointless, mindless, repetitive behavior – but as time went by, tail chasing in this breed and other breeds was labeled a compulsive disorder. I was never totally at ease with this diagnosis as some other issues also affected these dogs. For example, many affected dogs, especially males, also exhibited explosive aggression and the behavior seemed to run in lines prone to seizures. Others would “trance” – staring at walls or into space and would freeze under bushes or walk in slow motion (I called it moon walking).
A CAT scan of affected dogs showed hydrocephalus (“water on the brain”) and EEG recordings showed abnormal brain waves with an “epileptiform” pattern. Was it really a compulsive disorder or were things more complicated? For this reason we delayed looking at the genetics of affected dogs as we researched OCD in other breeds.
It turns out that the genetic glitch on other breeds with OCD – which pointed to a gene called neural cadherin (or CDH2) – was not involved in the bull terrier problem. So what was causing their issues? A large controlled phenotypic study of 333 bull terriers provided the answer. The tail chasing problem in bull terriers, as it turns out, was more common in males, and was associated with explosive aggression and trancing. There was also a loose association with fears and phobias and partial seizure-like behavior. Could the condition be a canine form of autism, we thought, because all these features are shared by children on the autistic spectrum?
A post-hoc study of a large cohort of these dogs showed that they we regarded by their owners as asocial – affected dogs significantly more so that their unaffected peers – and that they had a profound fixation with ojects (an obsession, if you will). Again, both features of autism. When we tried to publish the canine autism look-alike version of autism, we were rebuffed by the first journal. “Just because it looks like autism doesn’t mean that it is,” was the gist of their rebuttal.
We needed biomarkers to convince the doubting Thomases of the world. Linking up with a medical researcher specializing in autism, he told us that a peptide called neurotensin (NT) was elevated in autism. That and corticotrophin releasing hormone (CRH). So we blood sampled a number of tail chasing bull terriers and control and found, sure enough, that levels of NT and CRH were elevated in affected dogs. Now we were able to publish our results in a journal called Translational Psychiatry.
Furthermore, the canine version of autism responded to similar medications, specifically serotonin-reuptake inhibitors, like Prozac, and anticonvulsant therapies. Many affected dogs also had significant skin issues and gastrointestinal disturbances were often reported. Symptomatic treatment of these conditions was often employed. Luteolin, a flavonoid found helpful for such issues, common in children with autism, because its use for this purpose is not well known in veterinary circles.
Back to genetics. If CDH2 was not involved, what was? The answer to that question is not in at the time of writing, but we did find 2 suspicious peaks in the DNA of affected dogs by means of a genome wide association study (GWAS). One peak was on chromosome 4, encompassing a cadherin gene and the other was on the X chromosome. Cadherin genes have been implicated in autism. In people, a neurological issue called Fragile X syndrome, is known to be caused by a faulty gene on the X chromosome. Fragile X often manifests as autism and is regarded by some as the only known genetic cause of autism, accounting for some 10 percent of cases. Right now, we are sequencing a few affected bull terriers to compare with controls and hope to have the answer to the nagging question within 6 months (the statistical analysis takes ages).
A more thorough account of our experiences and findings in the quest to study bull terriers can be found in my forthcoming book, Pets On The Couch. But remember, we only studied the one breed because it presented itself to us with unanswered questions. It is always helpful to study one breed in detail because dog breeds are closed populations making genetic analysis more likely to come up with the goods. It is quite possible that other breeds with a similar syndrome are also affected – that remains to be seen. At least we seem have found the first canine model of autism and top psychiatrists and neurologists agree that our finding are real.
