As 1.6 percent of the U.S. population is afflicted with a lifetime prevalence of obsessive-compulsive disorder (OCD), which is “characterized by intrusive thoughts that produce anxiety (obsessions), repetitive behaviors that are engaged in to reduce anxiety (compulsions), or a combination of both,” according to the National Institute of Mental Health (NIMH). Researchers at the Cummings School of Veterinary Medicine have linked their studies of the canine compulsive disorder (CCD) genes in dogs to compulsive behavior disorders in humans, furthering understanding of human OCD and helping find a more effective cure for human patients.
Nicholas Dodman, a professor in clinical sciences at the Cummings School, and his team have been studying the genes of CCD — the counterpart to human OCD, and have recently found chromosome locations that correspond to the disorder’s severity, according to a Feb. 26 Tufts Now article. Their findings are published in the paper “Genomic Risk for Severe Canine Compulsive Disorder, a Dog Model of Human OCD.”Moreover, Dodman and his researchers have also tested certain medicines on dogs that have been proven effective.
According to Dodman, this is not his first time working with CCD. In fact, he has been interested in animal disorders before the 1990s.Dodman explained that he came upon this area of animal behavioral care by chance. In the 1980s, soon after he arrived at Tufts, he became involved in trying to eliminate repetitive, undesirable behaviors in horses, which are called stable vices. After giving the horses morphine, which turned out to be ineffective, the team gave the horses opioid blocker medication, which led to a reduction in the unwanted behaviors.Since that study, Dodman noted that he became interested in the genetic and neurochemical bases of animal behavioral disorders, specifically compulsive behavioral disorders. At the same time, he said he wondered how CCD could be related to human OCD.
In the 1990s and early 2000s, along withEdward Ginns of University of Massachusetts Medical School, Dodman collected genetic samples from several species of canines, felines, horses, etc. After several years of collection, Dodman, Ginns and others found the CDH2 gene in dogs of particular interest. When comparing this gene to the human version, it partially clarified the link between canine and human brains in regards to compulsive behavioral disorders, Dodman noted.
In addition to gene study, Dodman also compared the brains of both humans and dogs.In 2013, Dodman worked with Marc Kaufman from the McLean Hospital to image Doberman Pinscher and human brains and compare them with each other. Kaufman detailed what their goals were in an email to the Daily.
“Our general aim in animal studies is to try to identify brain structural and functional abnormalities similar to those reported in humans with compulsive behavior disorders, and then determine with imaging and other methods the underlying mechanisms for those abnormalities,” he wrote.
Kaufman also wrote about how dog models can be useful due to inbreeding and thus a lack of genetic variation makes genes easier to study and compare.
“All of these [canine brain] abnormalities paralleled those previously reported in human studies of patients with compulsive behavior disorders, and are consistent with brain circuit abnormalities thought to underlie compulsive behavior disorders,” Kaufman wrote.
Dodman and his team have also delved further into the neurochemical aspect of compulsive behavioral disorders. Specifically, Dodman said he became interested in selective serotonin reuptake inhibitors (SSRI), or drugs that increase the brain’s serotonin levels.According to him, these drugs (an example of which is Prozac), are frequently used to treat depression and anxiety. Dodman also noted that although these drugs did not help too much, identifying MMDA receptors finally aided in curbing dogs’ obsessive compulsive behaviors. These, along with the similarities between canine and human brains and genes, may open up the possibilities for future treatment options.
According to his most recently published paper, Dodman and his team have found several loci on the genes of canine chromosomes contribute to levels of CCD severity, which speaks more to the similarity between CCD and OCD and helps elucidate both conditions. However, he believes that there is more to be done. For example, according to him, there are abnormal serotonin receptor genes on CCD-afflicted dogs' chromosomes, as opposed to normal genes on dogs without CCD. To further progress this research, he also said there must be more exploration into the genetic pathways of human genes. He believes the same serotonin receptor genes should be analyzed more in humans with and without OCD.
“If you show that the same genes are involved [in both humans and canines], then you can make projections about genetic pathways [of each species],” Dodmansaid. “When you discover the pathway, then you will know more about the physiology of the problem and new methods of treatment."
Both canine and human compulsive behavior disorders are severe conditions that are necessary to treat. For dogs, Dodman noted that CCD can greatly disrupt the pet-owner relationship. He explained that canines can experience a variety of compulsive behaviors, such as object suckling and compulsive circling.
In humans, although the genetics and neurochemistry are similar, the behaviors are different but just as debilitating. Professor of Psychology Alexander Queen discussed the implications of the disorder in humans. According to Queen, although OCD was considered simply an anxiety disorder by the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), the latest version, DSM-5, currently has OCD in its own category along with disorders like hair-pulling and body dysmorphic disorders.
“Most of the time, people realize that [obsessive-compulsive] thoughts are unrealistic or not necessary, but they feel like they have to do them to reduce their anxiety,” he said.
Queen also talked about the various compulsive habits that reduce a person’s quality of life, including excessive hand washing and showering. He mentioned that not only does it take time out of people’s days, it prevents them from going certain places and hinders work and personal relationships.
Queen noted that both psychiatric and psychological treatment options exist.Medicines used to treat human OCD include SSRIs such as Zoloft and Prozac. Behaviorally, there is a type of cognitive behavioral therapy, named “exposure with response prevention," which gradually introduces and then maintains a fearful stimulus in order to habituate the patient.
Still, despite the current treatments at hand, Dodman believes that there is still much more science left undiscovered — science that can pave the way to even better, more effective treatments for both canines and humans. Kaufman agrees.
“Unfortunately, many patients are undertreated, or even worse, undiagnosed for many years after symptoms begin,” Kaufman wrote. “Our research aims to better understand brain developmental mechanisms, including identifying genes that increase vulnerability for developing a compulsive behavior disorder, which may enable earlier diagnosis and better treatment, of these debilitating conditions.”
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| Friday, November 22, 2024
