Mayo Clinic study reveals brain cell deficit behind Tourette syndrome

A new Mayo Clinic study finds that people with Tourette syndrome have about half as many of a specific type of brain cell that helps calm overactive movement signals as people without the condition. This deficit may be a key reason why their motor signals go unchecked, leading to the involuntary tics that define the disorder.

The study, published in Biological Psychiatry, is the first to analyze individual brain cells from people with Tourette disorder. The findings also shed light on how different types of brain cells may interact in ways that contribute to the syndrome's symptoms.

This research may help lay the foundation for a new generation of treatments. If we can understand how these brain cells are altered and how they interact, we may be able to intervene earlier and more precisely."

Alexej Abyzov, Ph.D., co-author, genomic scientist in Mayo Clinic's Center for Individualized Medicine

Tourette disorder is a neurodevelopmental condition that typically begins in childhood. It causes repeated, involuntary movements and vocalizations such as eye blinking, throat clearing or facial grimacing. While genetic studies have identified some risk genes, the biological mechanisms behind the condition have remained unclear.

To better understand what's happening in the brain with Tourette syndrome, Dr. Abyzov and his team analyzed more than 43,000 individual cells from postmortem brain tissue of people with and without the condition. They focused on the basal ganglia, a region of the brain that helps control movement and behavior. In each cell, they looked at how genes were working. They also analyzed how changes in the brain's gene-control systems might trigger stress and inflammation.

First, they found in people with Tourette syndrome a 50% reduction in interneurons, which are brain cells that help calm excess signals in the brain's movement circuits. They also observed stress responses in two other brain cell types. Medium spiny neurons, which make up most of the cells in basal ganglia and help send movement signals, showed reduced energy production. Microglia, the brain's immune cells, showed inflammation. The two responses were closely linked, suggesting the cells may be interacting in Tourette disorder.

"We're seeing different types of brain cells reacting to stress and possibly communicating with each other in ways that could be driving symptoms," says Yifan Wang, Ph.D., co-author of the study.

The study also provides evidence that the underlying cause of brain cell changes in Tourette disorder may be linked to parts of DNA that control when genes turn on and off.

"Tourette patients seem to have the same functional genes as everyone else but the coordination between them is broken," Dr. Abyzov says.

Next, the researchers plan to study how these brain changes develop over time and look for genetic factors that may help explain the disorder.

The study was conducted in collaboration with the lab of Flora M. Vaccarino, M.D., at Yale University. For a complete list of authors, disclosures and funding, review the study.