Dog Genome Studies Hold Promise for Human OCD Therapy

Veterinary and human medicine researchers have discovered genetic pathways that influence the severity of canine compulsive disorder, a finding that one day may lead to better therapies for obsessive compulsive disorder in humans.

“Dogs naturally suffer complex diseases, including mental disorders that are similar to those in humans. Among those is canine compulsive disorder (CCD), the counterpart to human obsessive compulsive disorder (OCD),” said the study’s first author, Dr. Nicholas Dodman, an animal behavior specialist and professor at Cummings School of Veterinary Medicine at Tufts University.

The finding appears online ahead of print in the International Journal of Applied Research in Veterinary Medicine.

OCD is one of the world’s most common neuropsychiatric disorders, affecting an estimated one to three percent of people and listed by the World Health Organization as among the 20 most disabling diseases.

OCD is often characterized by distressing thoughts and time-consuming, repetitive behaviors, while canine compulsions may include repetitive tail chasing, excessive grooming, and flank and blanket sucking.

Researchers note that current OCD therapies are not as effective as they could be; drug treatment benefits only about half of all human patients. No previously recorded study in humans or dogs has addressed the factors that drive severity in OCD and CCD.

“Genomic research on human neuropsychiatric disorders can be challenging due to the genetic heterogeneity of disease in humans,” said neurologist Edward Ginns, M.D., Ph.D., a professor at the University of Massachusetts Medical School and a co-author on the new study.

“Canine compulsive disorder shares behavioral hallmarks, pharmacological responsiveness, and brain structural homology with human OCD, and thus is expected to be an important animal model.”

The research team compared whole genome sequencing of 70 Doberman pinschers to search for inherited factors that exacerbate CCD. Researchers identified two loci on chromosomes that were strongly correlated with severe CCD, as well as a third locus that showed evidence of association.

The locus most strongly associated with severe CCD was found on chromosome 34, a region containing three serotonin receptor genes.

“This is particularly significant because drugs that work on the serotonin system are the mainstay treatment for OCD in humans, which demonstrates further correlation between the human and animal models,” said Dodman.

The second locus significantly correlated with severe CCD was on chromosome 11, the same chromosome that contains a gene thought to increase the risk of schizophrenia in humans.

This discovery, along with suggestive evidence found on chromosome 16 linking CCD to stress tolerance, may also be relevant to the pathophysiology of OCD, according to the study authors.

“Comparative genomics is a particularly attractive approach to reveal the molecular underpinnings of disease in inbred animals with the hope of gaining new insights into these diseases in dogs and humans,” Ginns said.

The study builds on more than a decade of research from Cummings School of Veterinary Medicine and the University of Massachusetts Medical School that in 2010 initially found the neural cadherin (CDH2) gene on canine chromosome 7 that appeared to coincide with an increased risk of OCD.

Additionally, 2013 MRI research from Cummings School of Veterinary Medicine at Tufts University and McLean Imaging Center at McLean Hospital showed that the structural brain abnormalities of Doberman pinschers afflicted with canine compulsive disorder (CCD) were similar to those of humans with OCD.

Use of canines to study OCD is a new approach that offers significant potential.

“If the canine construct is fully accepted by other OCD researchers, this spontaneously occurring model of the condition in humans, right down to the biological pathways involved, could help point the way to novel and more effective treatments for such a debilitating condition,” Dodman says.

Source: Tufts University
Genetics and brain photo by shutterstock.