Because it often goes undiagnosed, no one knows for sure how many people in the United States have Tourette Syndrome (TS), but the Tourette Syndrome Association estimates the number at around 200,000. People with TS exhibit a spectrum of tic disorders: They make sounds, sniff, blink or jerk their heads involuntarily — able to control the impulse for a moment or two, but ultimately unable to prevent the tics that characterize the disorder.

More is understood now than when the condition was named for French physician Georges Gilles de la Tourette, based on his 1885 description of the disorder, but what causes TS and how best to treat it remain a mystery.

Washington University researchers Kevin J. Black, MD, and Bradley L. Schlaggar, MD, PhD, would like to change that. They're leading a group of scientists attempting to bring together multiple resources at the School of Medicine to attack the problem. Their new pilot projects represent an early step on the road to making the university a national center of excellence in TS research and treatment.

Bradley L. Schlaggar, MD, PhD, and Kevin J. Black, MD, along with postdoctoral research associates Jessica A. Church, PhD, center, and Meghan C. Campbell, PhD, not shown, dedicate their research efforts to improving the lives of patients with Tourette Syndrome. These WUSTL researchers received more than one-sixth of all 2008–09 research grants made by the Tourette Syndrome Association.

"There are a handful of reasonable theories about what's happening in Tourette's," says Black, associate professor of psychiatry, neurology, neurobiology and radiology. "One is that in people with TS, certain parts of the brain are smaller, and that somehow contributes to tics. There are also one or two genes that may be involved, but how they affect patients isn't clear." Another theory is that a tic is a kind of habit that tends to perpetuate itself, and for whatever reason, it's very hard for some people to suppress it. A related hypothesis is that a tic can relieve discomfort for some people.

That's certainly true for Mark Elliot, a recent Washington University graduate and one of Black's TS patients. He describes his tics as "kind of like having an itch." And like an itch from a bug bite or scratch, it demands "scratching."

"That's how my teeth feel," Elliot says, before chomping his molars together, one of his tics. "I can't control the fact that I have an 'itch,' and I usually can take some control over when to 'scratch' it. But I know, eventually, I'm going to 'scratch.'"

Black says that up to 30 percent of children experience tics, but in TS patients like Elliot, those normally occurring tics persist. The reasons may be genetic or environmental, but tics that go away in most people become a regular, chronic event for a person with TS. To test his theory, Black is going into the community. A new grant from the Tourette Syndrome Association will help him identify kids with tics to figure out why those tics will develop and desist in some but remain in others.

"Almost all Tourette's research in the past has involved looking at a person who has had tics for five years and comparing that individual to someone the same age who never has had a tic," Black explains. This is true of his current NIH-funded study with co-investigator Tamara G. Hershey, PhD, associate professor of psychiatry, neurology and radiology, on how dopamine affects brain function in TS. "What we want to do now is find people whose tics have just started and then follow them."

The differences identified between those whose tics stop and those whose tics continue could allow Black's team to isolate some of the factors that contribute to TS. He is developing a video that features people who exhibit tics to show parents and teachers. "We should then be able to identify kids in the community at risk for TS who wouldn't normally be in treatment," he says.

Meanwhile, Schlaggar, the A. Ernest and Jane G. Stein Professor of Developmental Neurology, and associate professor of neurology, radiology, pediatrics, and of anatomy and neurobiology, is learning that the brain seems to function differently in people with TS, particularly when it should be relaxing. Schlaggar's laboratory uses a technique called resting-state, functional connectivity MRI, a brain imaging method that allows investigators to use spontaneous activity in the resting brain to put together a picture of the basic architecture of networks within that complex organ.

"Networks in the brain involved in attention appear immature or irregular in TS patients," says Schlaggar. "As we move forward, we'll use functional brain imaging to look at these networks as patients perform attention-demanding tasks."

Research like Black's and Schlaggar's may lead to better understanding of what causes TS, making it possible to treat its causes rather than its symptoms. Identifying symptoms earlier to begin treatments sooner also could make therapies more effective. "We need medications that address the root of these problems, rather than just the symptoms of the disease," Schlaggar says. He's currently treating TS patients with available medicines to see how they affect the immature and irregular networks that his functional brain imaging studies have identified. "One of our main hypotheses is that these medications to treat tics may be normalizing the brain networks that appear atypical or immature in TS patients," he explains. "We want to test that idea."

They want to test a lot of other ideas, too. So little is understood about TS that Schlaggar and Black say it's important to travel down many roads. They hope their current pilot projects will represent the first steps on that journey.