NEW HAVEN >> A cause of Tourette syndrome has been discovered, Yale scientists say, yielding a potential pathway to a cure for the debilitating disorder.
The researchers, studying a family of nine all of whom have Tourette, found a rare mutation in a gene that produces histamine in the brain. “It causes these brain abnormalities that causes Tourette, but only in rare cases,” said Christopher Pittenger, associate professor in psychiatry at Yale and in the Yale Child Study Center, and senior author of the paper, which is being reported Thursday in the journal Neuron.
However, the finding is important, he said. “We’ve shown something that prior to the genetics was completely unexpected … an entirely new system in the brain that we didn’t know was involved before.”
The scientists also studied mice with the same gene mutation and determined that it is a cause of Tourette, Pittenger said.
“It’s not THE cause of Tourette syndrome, just A rare cause,” Pittenger said. There could be other causes as well, he said. However, he said, “Eventually, it’s going to lead us to things that aren’t rare.”
Histamine, a compound in the brain that has several functions, is often associated with allergies. Still, “something is out of balance” in Tourette “but we don’t know exactly what’s going on in the brain,” Pittenger said.
Tourette occurs in 1 percent of children, many of whom grow out of it; its incidence in adults is less. The syndrome causes “little involuntary movements” called tics as well as involuntary speech. Pittenger said the symptoms may include such things as blinking, an inability to sit still or spontaneous yelling. Severe cases can result in self-harm, such as spinal damage from violent movements.
“Less extreme but much more common is, they can be very socially disruptive,” Pittenger said.
Among the connections that are known about Tourette are that it often accompanies attention-deficit disorder or obsessive-compulsive disorder. Its causes are about 50 percent genetic, he said.
“The most direct way that this may lead to treatment … is that drugs that target this may be more generally helpful, not only in this rare cause” but in other causes yet to be found.
“The other thing about Tourette’s is the treatments we have are not very good. … There’s very few people in the country that are successful with behavioral therapies. There’s a real need for new insights.” Drugs such as Haldol are also used to treat Tourette.
Pittenger said the finding of a mutation in the histamine gene, HDC, could be one of many originating causes. Say there are 50 in all. “If we can find the downstream things that all 50 of these causes lead to, then we can find treatments that are helpful for everyone,” he said.
Carol Mathews, who is on the medical advisory board of the Tourette Syndrome Association, cautioned that the study is limited in what it can tell researchers, though it “definitely adds to the knowledge base.”
The study’s usefulness is limited because the nine members of the family that has the mutation are the only subjects found so far. “It’s only going to be a very small proportion of the genetic causes of Tourette … and they say that,” said Mathews, who is professor of psychiatry at the University of California at San Francisco.
However, Mathews said “it’s not a huge piece of the puzzle but it’s a key piece of the puzzle, I would say.” She also called it “a beautifully done study.”
Where it will be helpful to future researchers, she said, is that the discovery of one mutation may lead to finding other mutations in other genes and ultimately a pathway that is implicated in Tourette.
Similar findings — “this approach of finding families with rare mutations” — led to major advances in finding the genetic causes of Alzheimer’s disease and autism, Mathews said.
“It’s led to a huge increase of what we understand about what is happening in the brain in people with autism,” although there are “1,000 genes” that are involved with that disorder.
The Yale study is “a very important tool that now enables us to look at the role of histamine … and how it might be involved in the role of movement disorders.
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