Brain changes linked to Tourette syndrome symptoms

[WORLD] A recent American study has revealed that individuals with Tourette syndrome possess roughly half the number of a particular brain cell type that helps suppress excessive motor activity, compared to those without the condition.

Researchers believe this shortfall could be a crucial factor in the unchecked motor signals that result in the involuntary tics characteristic of the disorder.

Published in the journal Biological Psychiatry, the study is the first to examine individual brain cells from people diagnosed with Tourette syndrome. The research offers new insights into how various brain cell types may interact in ways that give rise to the disorder’s symptoms.

Enabled by cutting-edge single-cell sequencing technology, the study allowed scientists to analyze gene activity with unprecedented precision. Previous investigations relied on broader imaging or tissue-level analysis, which lacked the resolution to isolate specific cellular differences. The findings underscore the growing impact of precision medicine in deepening our understanding of neurological conditions.

“This research may help lay the foundation for a new generation of treatments,” said Dr. Alexej Abyzov, a genomic scientist at the Mayo Clinic’s Center for Individualized Medicine and study co-author. “If we can understand how these brain cells are altered and how they interact, we may be able to intervene earlier and more precisely.”

Tourette syndrome is a neurodevelopmental disorder that typically emerges during childhood, marked by involuntary movements and vocalizations such as eye blinking, facial twitching, or throat clearing.

Although genetic studies have identified several associated genes, the biological underpinnings of the condition have remained largely elusive. Scientists have long theorized that Tourette syndrome stems from an imbalance between excitatory and inhibitory brain signals. The latest findings lend weight to that hypothesis, pointing to a lack of inhibitory interneurons as a possible driver of overactive motor circuits. This could explain why tics often intensify under stress, when the brain’s ability to regulate signals is compromised.

To probe the cellular mechanics behind Tourette syndrome, Dr. Abyzov and his team examined over 43,000 individual cells from postmortem brain tissue of both affected and unaffected individuals. Their focus was the basal ganglia, a brain region involved in movement and behavioral control. The team evaluated gene expression in each cell and assessed changes in the genetic regulatory systems tied to stress and inflammation.

While the basal ganglia have long been implicated in Tourette syndrome, previous studies could not determine whether observed changes were causal or secondary. By isolating single cells, the researchers provide more compelling evidence that these abnormalities are likely central to the disorder’s development.

Their analysis found a roughly 50% reduction in interneurons—cells responsible for dampening excessive signaling in the brain’s motor pathways—in people with Tourette syndrome. They also detected stress responses in two additional cell types.

Medium spiny neurons, which form the bulk of cells in the basal ganglia and play a key role in transmitting movement signals, showed signs of reduced energy metabolism. Meanwhile, microglia—the brain’s immune cells—exhibited inflammatory activity. These two responses appeared to be interconnected, suggesting potential communication between cell types in the manifestation of symptoms.

“We’re seeing different types of brain cells reacting to stress and possibly communicating with each other in ways that could be driving symptoms,” said co-author Dr. Wang Yifan.

The study also indicates that disruptions in regulatory regions of DNA—known as enhancers and suppressors—may underlie these cellular changes. These segments act as switches, controlling when and how genes are expressed. If they malfunction, critical genes may activate improperly, which could help explain why Tourette symptoms vary significantly among individuals.

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

The research team now plans to explore how these cellular and genetic changes develop over time, as they search for specific genetic factors that could further illuminate the roots of the disorder.