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By On September 17th, 2018

Study claims to have found key to identifying and treating OCD behaviors

Obsessive-compulsive disorder may be a widely recognized mental illness, but it is surprisingly poorly understood by much of the medical world. While we can identify the symptoms that arise from the disorder, the actual underlying mechanisms have largely been a mystery – until now.

New research from UCLA claims to have discovered some of the basic brain mechanisms that drive repetitive behavior in people, including those with OCD. The team, led by professor Baljit Khakh, believes the findings could pave the way toward better treatments for OCD and potentially other mental health issues.

The team uncovered this by focusing on a type of brain cell known as astrocytes. There is some belief that astrocytes act as “support cells” for the brain, but little is known about how this is done. The researchers were hoping that by exploring how astrocytes use calcium signaling to communicate with other cells.

“What we didn’t understand from earlier work was what those calcium signals actually did. We wondered, were they regulating neurons nearby, and if so, how,” said Khakh.

As a part of the study, the team intentionally reduced the output of astrocyte calcium signals in an area of the brain called the striatum. This area is largely related with movement and is commonly a problem area related to brain disorders.

By reducing the calcium signaling in healthy mice, the team was able to immediately alter their behavior. Specifically, the team says the mice began spending significantly more time in the corners of their cage.

Initially, the researchers believed this was a sign of anxiety or motor control issues, but tests of motor control and anxiety showed no change in the treated mice compared to untreated mice.

After further observation, Khakh and colleagues discovered the mice were actually participating in excessive compulsive cleaning. The mice were exhibiting self-grooming behaviors more than 450% more than the untreated mice.

“For months, we wondered why they spent so much time in corners. It turned out that they were spending a lot of time self-grooming,” said first-author of the study Xinzhu Yu. “This phenotype resembled very closely repetitive behaviors in humans; for example, the repetitive hand washing that happens with some OCD patients.

Notably, these behaviors were not found when the team reducing the calcium signaling in other areas of the brain.

This led the team to narrow in on the behavior of astrocytes in the striatum and run a number of tests to evaluate how calcium signaling played a role in their function. They found the astrocytes were actually regulating the activity of other nerve cells nearby though controlling levels of the neurotransmitter GABA in the striatum.

GABA is linked to Huntington’s disease, the early stages of which strongly resemble symptoms of OCD.

However, the team didn’t stop there. By giving the mice showing obsessive behaviors a compound to block an essential step in the calcium signaling process, the mice would stop excessive self-grooming.

“The fact that we could observe psychiatric-related phenotypes after astrocyte-specific manipulations was unexpected and hence a very pleasant surprise,” Khakh said. “As far as I know, this is the first demonstration that astrocytes can regulate an innate behavior and it opens the door for exploiting them for therapies aimed at mental illness.”

The findings are an early step towards not only better understanding OCD-related behaviors, but potentially treating those who have not responded to current treatments available.

“Many patients are non-responsive or partially responsive to the current available treatment options,” Khakh said. “Our findings point to a new direction for potential therapy development by revealing an involvement of astrocytes in repetitive behaviors that are related to OCD.”

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