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Researchers Publish Studies Of Obsessive-Compulsive Disorder And Tourette …

Two papers that will appear in the journal Molecular Psychiatry, both receiving advance online release, may help identify gene variants that contribute to the risks of developing obsessive-compulsive disorder (OCD) or Tourette syndrome (TS). Both multi-institutional studies were led by Massachusetts General Hospital (MGH) investigators, and both are the first genome-wide association studies (GWAS) in the largest groups of individuals affected by the conditions.

“Previous studies of these disorders have demonstrated that both TS and OCD are strongly heritable and may have shared genetic risk factors, but identification of specific genes has been a huge challenge,” says Jeremiah Scharf, MD, PhD, of the Psychiatric and Neurodevelopmental Genetics Unit (PNGU) in the MGH Departments of Psychiatry and Neurology, a co-lead author of both papers and co-chair of the Tourette Syndrome Association International Consortium for Genetics. “These new studies represent major steps towards understanding the underlying genetic architecture of these disorders.”

An anxiety disorder characterized by obsessions and compulsions that disrupt patients’ lives, obsessive-compulsive disorder (OCD) is the fourth most common psychiatric illness. Tourette syndrome, a chronic disorder characterized by motor and vocal tics, usually begins in childhood and is often accompanied by conditions like OCD or attention-deficit hyperactivity disorder. Both conditions have a high risk of recurrence in close relatives of affected individuals, but previous studies that compared affected and unaffected individuals were not large enough to identify specific genes or areas of the genome that contribute to risk.

Since many gene variants probably contribute to risk for both conditions, the research teams undertook GWAS investigations, which analyze hundreds of thousands of gene variants called SNPs (single-nucleotide polymorphisms) in thousands of individuals with and without the condition of interest. The International OCD Foundation Genetic Collaborative, consisting of more than 20 research groups in nine countries, analyzed almost 480,000 SNPs in 1,465 individuals with OCD, more than 5,500 controls and from 400 trio samples consisting of an OCD patient and both parents. The Tourette Syndrome Association International Consortium for Genetics and the TS GWAS Consortium, representing 22 groups across seven countries, analyzed 484,000 SNPs across almost 1,500 cases and more than 5,200 controls.

The OCD study – led by Evelyn Stewart, MD, of the MGH-PNGU, who is now based at the University of British Columbia, and David Pauls, PhD, MGH-PNGU – identified possible associations close to a gene called BTBD3, which is closely related to a gene that may be involved in Tourette Syndrome, and within DLGAP1, a close relative of a gene that produces OCD-like symptoms in mice if it is deleted. The Tourette study was led by Scharf and Pauls and found evidence of a possible association with a gene called COL27A1, which may be expressed in the cerebellum during development, and with variants that help regulate gene expression in the frontal cortex.

None of these or other identified SNPs reached the high threshold of genome-wide significance, which would indicate that the associations represented true risk factors, and the authors stress that additional, larger studies are required. “Although GWAS analysis allows much more comprehensive examination of the entire genome than do studies focused on particular families or candidate genes, these two studies are still underpowered and should be interpreted with caution,” says Pauls, a co-senior author of both papers. “The current results are interesting and provide us with a starting point for analyzing future studies that must be done to replicate and extend these findings.”

Scharf adds that the next steps should include testing the SNPs identified by these studies in other groups of patients and controls, analyzing both study groups together to identify genes that contribute to the risk of both disorders, and expanding international collaborations to increase the size and power of patient samples for both OCD and TS. “If future studies confirm that some of these variants do contribute to risk – either directly or by altering the function of other risk genes – that would suggest both novel disease mechanisms and might give us new treatment targets,” he says.

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Canine tail chasing resembles human obsessive compulsive disorders


The genetics research group, based at the University of Helsinki and the Folkhälsan Research Center and led by Professor Hannes Lohi, has in collaboration with an international group of researchers investigated the characteristics and environmental factors associated with compulsive tail chasing in dogs. A questionnaire study covering nearly 400 dogs revealed several similarities between compulsive behavior in dogs and humans: early onset, recurrent compulsive behaviors, increased risk for developing different types of compulsions, compulsive freezing, the of , the effects of early and and . The study shows that dogs offer an excellent animal model for studying the genetic background and environmental factors associated with human obsessive compulsive disorders (OCD). The study has been published in the journal PLoS ONE on July 27, 2012.

Stereotypical behavior in pets has not been studied extensively, even though several different types of compulsive behavior occur in different species including dogs. A dog may recurrently chase lights or shadows, bite or lick its own flank, pace compulsively or chase its own tail.

Different environmental and genetic factors have been suggested to predispose to compulsive behavior. Many stereotypes are breed-specific, which emphasizes the role of genes. Compulsive tail chasing occurs in several dog breeds, but worldwide it is most common in breeds such as Bull Terriers and German Shepherds.

The aim of this study was to describe the characteristics of tail chasing in dogs, to identify possible environmental risk factors, and to find out whether a previously discovered gene region associated with compulsive behavior is also linked to tail chasing.

Could vitamins have an influence?

Nearly 400 Finnish dogs participated in this study, including Bull Terriers, Miniature Bull Terriers, German Shepherds and Staffordshire Bull Terriers respectively. Blood samples were taken from the dogs participating in the study, and their owners filled out a questionnaire about their dogs’ stereotypic behavior. The questionnaire included questions about different stereotypic behaviors, as well as aspects of each dog’s puppyhood and the routines of the dog’s current daily life. In addition to this the owners evaluated their dogs’ personality based on the questions in the questionnaire.

The study included dogs that chased their tails daily for several hours, dogs that chased their tails a few times a month, and dogs that had observably never chased their tails. With most of the dogs, the tail chasing had begun at the age of 3 to 6 months, before reaching sexual maturity.

One of the most interesting findings of this study is the connection with stereotypic behavior and vitamins and minerals. Dogs that received nutritional supplements, especially vitamins and minerals, with their food, chased their tails less.

“Our study does not prove an actual causal relationship between vitamins and lessened tail chasing, but interestingly similar preliminary results have been observed in human OCD” says researcher, Katriina Tiira, PhD. Follow-up studies will aim to prove whether vitamins could be beneficial in the treatment of tail chasing.

Early separation from the mother and the mother’s poor care of the puppy were also found in the study to predispose dogs to tail chasing. Early separation from the mother has been discovered to predispose also other animals to stereotypic behavior, but this is the first time this connection has been made with dogs.

The amount of exercise the dogs received or the number of activities they engaged in did not, however, seem to have a connection with tail chasing. This could be comforting news to many owners of dogs with compulsive behaviors, since often the owners themselves or the dogs’ living environment may be blamed for these behaviors. Although frustration and stress are likely to be significant causes of the occurrence of stereotypic behavior in for example zoo animals, they may be of lesser significance when it comes to Finnish dogs that are walked regularly.

Tail chasing in dogs can be used as an animal model for studying the genetic background of OCD in humans

Compared to the control dogs, tail chasers suffered more from also other stereotypic behaviors. In addition, tail chasers were more timid and afraid of loud noises.

“Different types of compulsive behavior occur simultaneously in humans suffering from obsessive compulsive disorder or other diseases such as autism” explains the head of the study, Professor Hannes Lohi.

Dogs may turn out to be of significant use in investigating the causes of human psychiatric diseases. “Stereotypic behavior occurs in spontaneously; they share the same environment with humans, and as large animals are physiologically close to humans. Furthermore, their strict breed structure aids the identification of genes.”

The gene region previously associated with compulsive flank licking and biting in Dobermans was not found to be associated with tail chasing in any of the breeds in this study. The next aim of this research project is thus to discover new gene regions connected to tail chasing.

The study is part of a larger DOGPSYCH project, funded by the European Research Council, in which the genetic background of different anxiety disorders, such as timidity, and sound sensitivity are investigated, as well as their similarities with corresponding human diseases.

Journal reference:

PLoS ONE
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University of Helsinki
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