Scientists have identified genes involved in Obsessive Compulsive Disorder (OCD) in dogs. The results, published in the journal Genome Biology, identify four genes strongly linked with canine OCD, and suggests that using dogs as a simplified model of the human condition might open up new avenues for research into the more complex human OCD.
OCD affects 1-3% of humans, but in dogs, particular breeds are more susceptible than others. Similarly to human OCD, the dog version of the condition involves repeating normal behaviours. While typically in humans, these might be hand washing or cleaning, checking or hoarding, canine symptoms include repeated grooming, constantly chasing their own tails or shadows and suckling or blanket sucking.
Existing mouse models of OCD are initiated by genetic manipulation, but the authors of this study thought that the dog version might be a good model of the human condition, because it occurs naturally, and, like in humans, symptoms can be relieved with SSRI or clomipramine antidepressants. The scientists from institutions including the Broad Institute and Uppsala University used a range of techniques to narrow down the regions of the genome involved in OCD to pinpoint four genes which were consistently linked to the disease in a range of dog breeds that are particularly susceptible to OCD – Doberman pinschers, bull terriers, Shetland sheepdogs and German shepherds.
‘It is intriguing that the clinical presentation and treatment strategies for OCD are so similar between dogs and people’ says co-senior author Kerstin Lindblad-Toh, professor at Uppsala University and Broad Institute, ‘We therefore designed our study to take advantage of comparisons between the behaviour in dogs and humans.’
The first step was a genome-wide association study (GWAS) of Doberman pinschers to identify regions of the genome to study. They then sequenced these regions of the genomes of dogs in all four breeds - eight that displayed OCD symptoms and eight that didn’t. This identified specific genetic variations known as ‘case only variants’ - genetic mutations that were present in at least one of the OCD dogs, but in none of the healthy control dogs. They tested these case only variant mutations in 69 more dogs from breeds susceptible to OCD and 19 from unsusceptible breeds for the mutations. Four genes showed a high number of mutations linked with OCD susceptibility, CDH2, PGCP, ATXN1 and CTNNA2, suggesting that these genes might be involved in causing the disorder.
Hyun Ji Noh, an author of the paper from the Broad Institute (USA) says: ‘The top candidate genes with most case-only mutations in our study are all involved in synapse formation and function. This suggests that disruption of synapse formation and function may play a key role in OCD. Other studies have suggested that dysregulation of certain brain regions may be responsible for the repetitive thoughts and behaviors in OCD. Taken together, compulsive dogs with unfavorable mutations in these genes may have disrupted synapse formation in the OCD-implicated brain regions, in turn manifesting uncontrollable repetitive canine behaviors.’
This proof of concept study shows that dogs with OCD can be a good model for human OCD, but more study is needed to elucidate whether these genes are involved in human OCD, and to identify ways that these findings can be used to improve treatments.
Elinor Karlsson, a senior author of the paper says: ‘By finding the genetic variants that cause OCD in dogs, we hope to understand more about the underlying neural pathways. Therapies and drugs used to treat OCD today often don’t work very well in dogs or in humans. If we can figure out precisely which brain circuits are disrupted in OCD patients, this could lead to more effective and targeted treatments.’
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Candidate genes and functional noncoding variants identified in a canine model of obsessive-compulsive disorder
Tang R, Noh H, Wang D, Sigurdsson S, Swofford R, Perloski M, Duxbury M, Pattersson N, Albright J, Castelhano M, Auton A, Boyko A, Feng G, Lindblad-Toh K and Karlsson E
Genome Biology 2014, 15:R25
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