Study finds cellular differences in Tourette patients’ brain tissue

The biological roots of Tourette disorder occur in the basal ganglia, structures deep in the brain involved in the control of movement—particularly learned motor routines and habits. However, the role of individual cells in triggering the involuntary body and vocal tics that characterize the disorder have not been well understood.

A new single-cell analysis led by researchers at Yale School of Medicine and the Mayo Clinic, and published in the journal Biological Psychiatry, has implicated several potential culprits associated with the disabling disorder, which affects as many as 1 in every 150 children.

The team led by corresponding author Flora Vaccarino, the Harris Professor at the Yale Child Study Center and professor of neuroscience at Yale School of Medicine, analyzed basal ganglia tissue from six individuals who had severe cases of Tourette disorder and compared those cells with tissue from six individuals without the disorder.

They found 50% fewer interneurons in the group with Tourette disorder. These interneurons are brain cells that suppress electrical activity within the basal ganglia to precisely modulate movements, which may explain motor hyperactivity in Tourette patients.

The researchers also found that medium spiny neurons—brain cells that make up 90% of cells in the basal ganglia—showed signs of metabolic stress in individuals with Tourette disorder. And finally, they observed that a type of immune system cell known as microglia showed increased inflammatory activity in basal ganglia tissue of those with the disorder; this inflammatory response, they found, was directly correlated with the metabolic stress in the medium spiny neurons.

“These factors create a pattern that may explain why individuals with Tourette disorder experience involuntary movements and vocalizations,” Vaccarino said.

Vaccarino also noted these cellular differences in Tourette patients appeared to be caused by changes in the expression of genes, not in alterations to the genes themselves.

“This insight opens up new directions for future research,” she said.