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See Inside June 2011

Treating Tourette's: Histamine Gene May Be Behind Some Tic Disorders

A genetic mutation causes low histamine levels to be produced



Illustration by Thomas Fuchs

Tourette’s syndrome is most pronounced in children. The physical and vocal tics, which can alienate kids from peers, are difficult to treat. First-line drugs are limited in their efficacy, whereas more effective antipsychotics have many potential long-term side effects, including weight gain and movement disorders. Investigators may be moving closer to a new treatment option involving drugs that already exist.

Last year researchers identified a new gene mutation associated with the disorder. Known mutations have only explained a small number of Tourette’s cases, so the investigators, led by Matthew State, co-director of the Yale Neurogenetics Program, studied a rare family in which the father and his eight children all had Tourette’s. In these family members, the gene involved in the production of histamine in the brain was shorter than normal, generating lower levels of the compound, which is involved in inflammatory response. State believes these lower levels can cause tics, and he is looking for this and further histamine-related mutations in other people with Tourette’s.

Now scientists have found parallels between this family and histamine-deficient mice, which furthers the connection to Tourette’s. Most individuals with Tour­ette’s have low prepulse inhibition, meaning that they are more easily startled or distracted than the average person, says Christopher Pittenger, director of the Yale OCD Research Clinic. In May he was to pre­sent new data to the Society of Biological Psychiatry that both this family and mice missing the histamine gene had low prepulse inhibition and tics. Other experiments have shown that histamine-boosting drugs decrease ticlike behaviors in mice.

Histamine is known for contributing to allergic reactions and keeping us awake at night, which is why antihistamines are available over the counter. But it is also a neurotransmitter found throughout the brain, including in a region associated with Tourette’s.

The findings suggest an alternative to antipsychotics, which reduce tics by blocking dopamine. As dopamine levels drop, histamine levels rise. Increasing histamine directly, without blocking dopamine, may work as well and avoid many of the side effects of antipsychotics. “Other people with Tourette’s may have other changes in their histamine system, so it’s quite possible that a histamine-boosting drug may have benefits, but it’s still very early,” says Kevin McNaught, vice president for medical and scientific programs at the New York–based Tourette Syndrome Association.

Drugs that increase histamine are already being tested to treat other neurological conditions, as well as attention-deficit hyperactivity disorder, which is often found in people with Tourette’s.

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