Tourette Syndrome: Histamine May Play a Role

Researchers under  Dr. Matthew State, an associate professor of child psychiatry, psychiatry and genetics at Yale University School of Medicine. have been studying the genome of  a family in which the father and all eight of his children have Tourette Syndrome  and have identified a mutation on the HDC gene that encodes the enzyme L-histidine decarboxylase, which is involved in regulating levels of the neurotransmitter histamine in the central nervous system.

This research provides clues to treating Tourettes Disorder, a neurological disorder that can cause debilitating, involuntary motor and verbal tics.

While the variant itself is likely very rare — meaning most people with Tourette syndrome don’t have the precise mutation — what’s known about the gene’s function in the body hints at new treatments, researchers explained.

Previous research in mice has shown that manipulating brain levels of histamine by decreasing activity of HDC makes mice more likely to have repetitive behaviors, such as biting, rearing and chewing, which may be similar to tics in humans.

Drugs that increase the release of histamine in the brain, but don’t affect histamine levels in other parts of the body, are in the latter stages of development. Previous research has shown that when given to mice, these drugs decrease the repetitive behaviors. It’s possible those drugs could also help people with Tourette syndrome.

Genetics may point to the function of the gene, which points to what kind of mechanisms might be involved in the disorder.

The study is published in the New England Journal of Medicine.

Tourette syndrome tends to run in families. The disorder usually emerges in childhood and, for some, improves in adulthood. Although the causes of the syndrome are unknown, previous research suggests abnormalities in certain brain regions and in the neurotransmitters dopamine, serotonin and norepinephrine may play a role.

Children who see doctors for Tourette syndrome often have other disorders as well, including depression, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder or learning disabilities.

Many cases of Tourette syndrome are mild and improve over time. But severe cases can be debilitating — socially and physically — and current treatment options are limited.

In addition to behavioral intervention, first-line medications include antidepressants and anti-anxiety medication. More severe symptoms of the syndrome can be treated with antipsychotic medications such as risperidone (Risperdal) or neuroleptic medications, such as haloperidol (Haldol), but long-term side effects can be serious.

The mutation identified in this family may be unique to them, but suggests the likelihood that functional differences in the  HDC gene or in the histamine biochemical pathway would play a role in other families affected by Tourettes.

SOURCES: Matthew State, M.D., Ph.D., associate professor, child psychiatry, psychiatry and genetics, Yale University School of Medicine, New Haven, Conn.; Francis J. McMahon, M.D., chief, Genetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, Bethesda, Md.; May 5, 2010, New England Journal of Medicine, online

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