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
[google_news title=”” keyword=”obsessive-compulsive disorder” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Obsessive-compulsive disorder
- Care Plan Your Doctor Would Usually Recommend For Obsessive Compulsive Disorderon May 9, 2024 at 2:28 pm
Overview A mental health disorder characterized by repetitive actions that seem impossible to stop. Symptoms Symptoms are either obsession or compulsion, or both. → Common treatment options → ...
- Deep brain stimulation didn’t work for a young OCD patient until new brain maps changed everythingon May 9, 2024 at 11:01 am
Five years ago, in a wheelchair, Julia Hum was admitted to a state mental hospital in Massachusetts. After treatment with targeted deep brain stimulation, she hopes to walk out soon and, for the first ...
- What Max’s Turtles All the Way Down Gets Right (& Wrong) About Latina Teens With OCDon May 9, 2024 at 9:23 am
Aza Holmes (Isabela Merced) can’t stand her own thoughts about bacteria and germs anymore. Despite doing therapy for her diagnosis of obsessive-compulsive disorder (OCD), the 16-year-old high schooler ...
- What Turtles All the Way Down Gets Right About OCDon May 8, 2024 at 9:35 pm
The book “Turtles All the Way Down” helped me feel seen during my early battles with OCD. Does the movie represent the mental health condition as well?
- Obsessive compulsive disorder and psychodynamic psychotherapyon May 8, 2024 at 1:13 am
Obsessive compulsive disorder (OCD) is a mental health condition consisting of obsessions and compulsions that have a significant impact on a person's life. Obsessions are unwanted and intrusive ...
- OCD, existentialism drive ‘Turtles All the Way Down’ adaptationon May 7, 2024 at 11:34 pm
The newest John Green adaptation follows a unique protagonist with a severe case of obsessive-compulsive disorder.
- Optimizing deep brain stimulation for obsessive-compulsive disorder - a free webinar from the Brain & Behavior Research Foundationon May 7, 2024 at 5:00 pm
The Brain & Behavior Research Foundation (BBRF) is hosting a free webinar, “Optimizing Deep Brain Stimulation for Obsessive-Compulsive Disorder” on Tuesday, May 14, 2024, at 2:00 pm ET. The presenter ...
- EXCLUSIVE: John Green recalls how OCD struggles as a teen inspired ‘Turtles All the Way Down’on May 3, 2024 at 4:01 am
John Green wants to change the perception of OCD and hopes the movie version of his novel creates a more nuanced look at people living with the mental health condition.
- I have OCD. Some cognitive behavioral therapy techniques were totally wrong for meon April 30, 2024 at 4:00 am
Many practitioners consider CBT the gold standard of therapy, but does it work for everyone?
- Type A Personality vs. Obsessive-Compulsive Personality Disorder vs. OCDon April 29, 2024 at 11:45 am
In addition, Type A personalities are defined by their impatience and need for speed; in contrast, those with OCPD are not concerned with time and efficiency as long as everything is “right.” In fact, ...
via Bing News