Brain receptor acts as switch for OCD symptoms in mice
A single chemical receptor in the brain is responsible for a range of symptoms in mice that are reminiscent of obsessive-compulsive disorder (OCD), according to a Duke University study that appears online in the journal Biological Psychiatry.
The findings provide a new mechanistic understanding of OCD and other psychiatric disorders and suggest that they are highly amenable to treatment using a class of drugs that has already been investigated in clinical trials.
“These new findings are enormously hopeful for considering how to approach neurodevelopmental diseases and behavioral and thought disorders,” said the study’s senior investigator Nicole Calakos, M.D., Ph.D., an associate professor of neurology and neurobiology at the Duke University Medical Center.
OCD, which affects 3.3 million people in the United States, is an anxiety disorder that is characterized by intrusive, obsessivethoughts and repeated compulsive behaviors that collectively interfere with a person’s ability to function in daily life.
In 2007, Duke researchers (led by Guoping Feng, who is now at the Massachusetts Institute of Technology) created a new mouse model of OCD by deleting a gene that codes for Sapap3, a protein that helps organize the connections between neurons so that the cells can communicate.
Similar to the way some people with OCD wash their hands excessively, the Sapap3-lacking mouse grooms itself excessively and shows signs of anxiety. Although researchers praised the new model for its remarkable similarity to a human psychiatric disorder, and have begun using it to study OCD, questions remain about how the loss of the Sapap3 gene leads to the grooming behaviors.
In the new study, Calakos’s team found that overactivity of a single type of receptor for neurotransmitters — mGluR5, found in a brain region involved in compulsive behaviors — was the major driver for the abnormal behaviors. When researchers gave Sapap3-lacking mice a chemical that blocks mGluR5, the grooming and anxiety behaviors abated.
“The reversibility of the symptoms was immediate — on a minute time frame,” Calakos said. In contrast, the original study describing Sapap3-lacking mice found that antidepressants could help treat symptoms but on the time scale of weeks, as is typical with these drugs in patients.
The immediate effects seen in the new study were also surprising, given that the brains of these mice appear developmentally immature and neurodevelopmental diseases are not typically thought of as being easily reversible, Calakos said.
Intriguingly, by taking normal laboratory mice and giving them a drug that boosted mGluR5 activity, Calakos’s team could instantaneously recreate the same excessive grooming and anxiety behaviors they saw in the Sapap3-lacking mice.
The researchers found that without a functioning Sapap3 protein, the mGluR5 receptor is always on. That, in turn, makes the brain regions involved in compulsion overactive. In particular, a group of neurons that give the “green light” for an action, like face-washing, is working overtime. (These same neurons can promote a habit, such as eating sweets, according to a study published by Calakos’s team earlier this year.)
Calakos said that mGluR5 should be considered for the treatment of compulsive behaviors. “But which people and which compulsive behaviors? We don’t know yet,” she added.
Other lines of research have explored targeting mGluR5 with drugs to move its activity up or down in the brain. For example, mGluR5-blockers are being considered for the treatment of Parkinson’s disease. But because mGluR5 inhibitors have not always panned out in clinical trials, it may make sense to target different parts of the mGluR5 pathway or identify specific patient subsets, Calakos said. New non-invasive imaging technologies now make it possible to measure mGluR5 activity in humans.
Learn more: Study Points to Fast-Acting Drug for OCD
The Latest on: Obsessive-compulsive disorder
via Google News
The Latest on: Obsessive-compulsive disorder
- We must prioritize our mental healthon October 10, 2020 at 10:08 am
I attended an event hosted by the National Alliance on Mental Illness (NAMI) called “Hear Our Voices: Personal Stories of Mental Health.” The event was part of NAMI’s campaign, #IWillListen, for ...
- Nickel: This new mental health campaign is what we need right now, in sports and in Wisconsinon October 9, 2020 at 9:23 pm
For many, mental health equates to shame, humiliation and vulnerability, when really it could be an opportunity to ask for help and find joy again.
- UAE mums' COVID mental health crisis - and where to turn for helpon October 9, 2020 at 9:00 pm
They include postpartum depression, postpartum anxiety, postpartum obsessive compulsive disorder, postpartum bipolar, and postpartum psychosis. During self-isolation in the pandemic, it’s never been ...
- World Mental Health Day 2020: 70% hike in number of patients suffering from depression, obsessive-compulsive disorder amid corona crisison October 9, 2020 at 4:30 pm
On World Mental Health Day, we discuss various issues and bring in expert suggestions. This year’s World Mental Health Day, on October 10, comes at a time when our daily lives have changed ...
- What Psychedelic Mushrooms Are Teaching Us About Human Consciousnesson October 9, 2020 at 10:47 am
Psychedelic drugs like psilocybin are being tested to treat mental illness. They're also expanding our understanding about human consciousness.
- COVID-19 and mental health in UAE: Do you suffer from Obsessive Compulsive Disorder?on October 9, 2020 at 9:02 am
Dubai: With this year’s World Mental Health Day (October 10) coming amid the pandemic, the debilitating mental impact that COVID-19 has had on some people has become a subject of much discussion.
- Digital Health Startup Raises $12 Million To Provide Virtual OCD Treatmenton October 8, 2020 at 5:12 am
To fulfill that mission, the Chicago-based digital health company announced it had raised a $12 million Series A round on Thursday. “We're telling the OCD community, no matter where you live or how ...
- Living with severe obsessive-compulsive disorderon October 8, 2020 at 3:01 am
Awareness month, and I share my story now with the hope of raising consciousness about OCD in the Middlebury community.
- Depression is major growing mental disorderon October 7, 2020 at 1:31 am
Depression is becoming the commonest mental health disorder affecting more than 400 million of 1.3 billion (31 per cent) people in Africa in all age groups. An estimated one in six people in Uganda ...
- Yle survey: More than 70 top Finnish athletes report mental health disorderson October 3, 2020 at 6:05 am
More than 70 top Finnish athletes reported that they suffered from mental health issues during the course of their careers, according to an extensive survey conducted by Yle Sport. A total of 111 ...
via Bing News