A new model of obsessive-compulsive disorder (OCD) that mirrors both symptoms of the disease and the timing of its treatment in humans has been created by University of Chicago researchers, according to a new study.
Using the model, researchers isolated a single neurotransmitter receptor in a specific brain region responsible for their model's OCD-like symptoms, offering new insight into the cause of the disorder. Further research with the model may point the way to new treatments for both OCD and autism, said Nancy Shanahan, PhD, lead author of the paper in Biological Psychiatry.
"Treatment for these people is greatly needed, and there really are very few highly valid animal models of the disorder," said Shanahan, a postdoctoral researcher at the University of Chicago. "Having one that seems to mimic the disorder so well, especially in terms of the time course of treatments that work in humans, is potentially very useful for researching novel therapeutics."
Stephanie Dulawa, PhD, assistant professor in the Department of Psychiatry and Behavioral Neuroscience at the University of Chicago Medical Center and senior author of the study, said, "Our model can make accurate predictions about what you see in OCD, and that gives us confidence that the underlying neurobiology is likely to be similar between the model and the actual disorder."
About 2.2 million people in the United States have been diagnosed with OCD, according to the National Institute of Mental Health. OCD patients struggle with repetitive rituals (such as hand-washing, counting and cleaning) and unwanted thoughts that can cause severe anxiety.
Psychiatrists have found some success treating patients with a class of drugs called serotonin reuptake inhibitors (SRIs) initially developed for depression. However, these drugs fail to reduce symptoms in as many as 60 percent of OCD patients and require four to eight weeks of treatment for therapeutic effects to begin.
"OCD is very mysterious and very prevalent," Shanahan said. "The development of OCD-specific treatments will be an extremely important step toward helping these people and preventing the disorder's cost to society."
With an animal model that replicates at least some aspects of OCD, researchers can dig deeper into the specific neurotransmitters and systems involved in the disorder. In Dulawa's laboratory, a team led by Shanahan found inspiration in a drug that activates the 1b class of receptors for the neurotransmitter serotonin. Clinically, the drug is used to treat migraines, but it is also known to have the unintended effect of increasing anxiety and compulsions in people with OCD.
When the drug was given to mice, they showed highly repetitive patterns of locomotion when placed into an open arena. The drug-treated mice also exhibited deficits in prepulse inhibition, a form of startle plasticity thought to measure the brain's ability to filter out intrusive thoughts, which plague OCD patients.
To determine whether these drug-induced behaviors reflected the neurobiology of OCD, the researchers tested the same drugs used to treat the disorder in humans. After four weeks of pre-treatment with SRIs — the same duration required to see therapeutic effects in humans — drug-induced OCD behaviors were reduced in the mice. Shorter SRI treatment or treatment with other antidepressant drugs that do not work in humans with OCD were unsuccessful in reducing the behaviors caused by the drug.
"We have this time course that nicely parallels or mimics the human therapeutic response," Shanahan said. "In order to study how these drugs are working and the pathophysiology of the disorder, we need a model where this delayed onset exists. So we are really excited about that."
The researchers then looked for a specific brain region where activation of 1b serotonin receptors creates OCD-like symptoms. In humans, scientists have identified a region called the orbitofrontal cortex that is more active in OCD subjects. Again matching the human data, selectively activating 1b receptors in the orbitofrontal cortex with the drug was sufficient to produce the OCD-like symptoms in the mice.
"We found that the 1b receptors in the orbitofrontal cortex were really the critical receptors," Dulawa said. "It was very affirming to our research because it is the brain region most heavily implicated in OCD throughout all of the human literature."
The results offer promising ideas about developing new treatments for OCD. A drug that blocks the serotonin 1b receptors may be effective in reducing OCD symptoms; however, no such chemical is currently available, Dulawa said. Alternatively, treating OCD patients with an activator of these receptors may exacerbate symptoms initially, but have long-term benefits as the number of serotonin 1b receptors decreases from over-stimulation.
"These treatments could potentially be much more specific and work much faster," Dulawa said. "Now that we have this model, we actually could pursue these ideas for better treatments in a disease where there is only one successful therapy."
The paper, "Essential role for orbitofrontal 5-HT1B receptors in OCD-like behavior and SRI response in mice," was published online September 15, 2011 by Biological Psychiatry (doi:10.1016/j.biopsych.2011.07.032). In addition to Shanahan and Dulawa, authors include Lady P. Velez of the University of Chicago and Virginia Masten of University of California, San Diego.
Funding for this work was provided by the National Institute of Mental Health.
For more news from the University of Chicago Medical Center, follow us on Twitter at @UChicagoMed, or visit our Facebook page at http://www.facebook.com/UChicagoMed, our research blog at http://sciencelife.uchospitals.edu, or our newsroom at http://www.uchospitals.edu/news/.
Robert Mitcum | EurekAlert!
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
25.04.2017 | Physics and Astronomy
25.04.2017 | Materials Sciences
25.04.2017 | Life Sciences