Mayo Clinic Identifies Key Brain Cell Deficiency Linked to Tourette Syndrome

Researchers at the Mayo Clinic have discovered a significant difference in the brains of individuals with Tourette syndrome, potentially unlocking the mystery behind the involuntary tics that characterize the neurodevelopmental disorder. The study, published in Biological Psychiatry, reveals that people with Tourette syndrome have approximately 50% fewer interneurons—a type of brain cell responsible for calming excessive movement signals—compared to individuals without the condition.

Led by Dr. Alexej Abyzov, a genomic scientist at the Mayo Clinic's Center for Individualized Medicine, this research marks the first time individual brain cells from people with Tourette syndrome have been analyzed at such a detailed level. “If we can understand how these brain cells are altered and how they interact, we may be able to intervene earlier and more precisely,” said Dr. Abyzov.

Tourette syndrome typically begins in childhood and manifests through repetitive, involuntary movements and vocalizations, such as facial grimacing or throat clearing. Although previous genetic studies have identified risk genes, the biological mechanisms behind the disorder have remained elusive.

Dr. Abyzov's team analyzed over 43,000 individual cells from postmortem brain tissue of individuals with and without Tourette syndrome, focusing on the basal ganglia—a region critical for controlling movement. Their investigation revealed not only a sharp decrease in interneurons but also other cellular responses indicating broader dysfunction.

Key findings include:

• Interneurons were significantly reduced, limiting the brain’s ability to suppress overactive motor signals.

• Medium spiny neurons, which are crucial for transmitting movement signals, showed signs of reduced energy production.

• Microglia, the brain’s immune cells, exhibited signs of inflammation—a response potentially tied to cellular stress.

The study suggests that interactions between these stressed cells could be contributing to the symptoms of Tourette syndrome. “We’re seeing different types of brain cells reacting to stress and possibly communicating with each other in ways that could be driving symptoms,” explained co-author Dr. Yifan Wang.

Notably, the researchers also identified that the root cause of these changes may lie not in the structure of the genes themselves, but in the regulatory elements—the regions of DNA that control when genes are activated or deactivated. “Tourette patients seem to have the same functional genes as everyone else, but the coordination between them is broken,” Dr. Abyzov noted.

Looking ahead, the team plans to explore how these brain cell changes evolve over time and to investigate genetic and epigenetic factors that could provide further insight into the condition. Their work may pave the way for more targeted and early-stage interventions for those affected by Tourette syndrome.