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