Best known for triggering symptoms of hay fever, histamine also acts as a neurotransmitter in the brain. A new genetic study led by Matthew W. State, M.D., Ph.D., the Donald J. Cohen Associate Professor of Child Psychiatry, suggests that histamine plays a role in Tourette’s syndrome.
As reported in the May 20 issue of The New England Journal of Medicine, in a rare family in which the father and all eight children, but not the mother, have Tourette’s, affected family members all carried the same mutation in HDC, a gene involved in histamine synthesis.
Normally, HDC molecules pair up in a symmetrical complex to synthesize histamine. The mutation, which truncates the HDC protein, is found on only one of two chromosomes, and inhibits the enzymatic activity of the normal copy by forming an abnormal complex.
Histamine-boosting drugs reduce Tourette’s-like behaviors in mice lackingHDC, and several are in human clinical trials for neuropsychiatric conditions, says State, also co-director of the Yale Neurogenetics Program. “This may mean that we have the opportunity to go directly from a rare genetic finding to a trial of a new approach to treatment. In our field, that would be very unusual, and very exciting,” he says.