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What Makes Tics Tick?
Clues Found in Tourette Twins' Caudates

August 1996

For the first time, scientists have a neurobiological explanation for the variation in severity of tics in Tourette Syndrome. Researchers at the National Institute of Mental Health have traced such symptom differences to "supersensitivity" of certain neurotransmitter receptors in the brain structure responsible for carrying out automatic behaviors. They suggest that this dysfunction may underlie the compulsion to act out the sudden movements and vocalizations that characterize Tourette Syndrome, which affects about 100,000 Americans with its full-blown form and up to 0.5% of the population with milder symptoms. The researchers report on their findings in the August 30th issue of Science.

In a brain imaging study of identical twins differently affected by the disorder, Daniel Weinberger, M.D., Steven Wolf, M.D., and colleagues in the NIMH Clinical Brain Disorders Branch found that binding to D2 dopamine receptors in the caudate nucleus was higher in the sibling with the more severe symptoms.

"Strikingly, the degree to which the twins differed in this caudate D-2 binding predicted almost absolutely their differences in tic severity," said Weinberger. "This also likely explains the ebb and flow of tics experienced over the course of Tourette Syndrome and its overlap with obsessive compulsive disorder.

"While we know that genetics plays an important role in transmission of Tourette Syndrome, the fact that identical twins show differences in symptom severity suggests that environmental influences modify the clinical expression of the disorder," he explained. "We studied identical twins discordant for such symptom severity to control for normal genetic variation in brain function."

Although previous studies comparing unrelated Tourette patients with unaffected persons had failed to show differences in dopamine system function, the NIMH investigators were spurred by the fact that Tourette symptoms respond to drugs like haloperidol that block D2 dopamine receptors. They used a radioactive tracer drug, IBZM (iodobenzamide), that similarly blocks D2 receptors, and a SPECT* (single-photon emission computed tomography) scanner to image dopamine binding in five identical twin pairs with the disorder.

In each case, the differences were observed in the head of the caudate nucleus, but not in the adjacent putamen, suggesting that D2 caudate binding accounted for almost all of the symptomatic variance within each twin pair. Previously, preoccupation with the motoric aspects of Tourette Syndrome had led researchers to search for clues in the putamen, according to Weinberger. Subtle changes in receptor availability in one small area appear to explain rather large differences in clinical presentation, say the researchers.

Functional brain imaging studies of OCD (obsessive compulsive disorder), which often occurs along with Tourette Syndrome, also implicate a brain circuit that includes the head of the caudate nucleus, along with areas in the frontal and cingulate cortex. Thus, the new NIMH finding adds to evidence that the disorders are "overlapping neurobehavioral conditions," suggest the researchers. They speculate that the caudate nucleus may be related to the compulsive component of tics, whereas the dopamine dysfunction there may be the "common link between the ideational and motor components of Tourette Syndrome."

Other NIMH researchers participating in the study included: Drs. Douglas Jones, Michael Knable, Thomas Hyde, Richard Coppola, Kan Sam Lee, and Julia Gorey.

Twin subjects were recruited by the Tourette Syndrome Association, Inc., which also provided partial funding for the study. Additional information and b-roll are available from the association (718-224-2999).

Information provided by the NIMH.

*The SPECT scanner employs radiation detectors to get a fix on the location in the brain of a tracer drug. Unlike other similar techniques, such as PET (positron emission tomography), SPECT uses a tracer with a long half-life, making possible studies such as this one, which involved a prolonged series of scans over a 4-hour period.