Thus, a young woman describes her ex-boyfriend who had Tourette syndrome (TS), the impact of which caused their breakup. TS affects approximately 1 in 100 Americans and is marked by a fluctuating course of multiple motor and phonic tics,1,2 which can have devastating social, physical, and psychological consequences for the patient.
TS commonly first appears as tics between the ages of 7 and 15 years and is more common in boys, explained Shubhangi Chitnis, MD, assistant professor of pediatric neurology at West Virginia University School of Medicine in Morgantown. Typically, TS intensifies during adolescence and subsides by adulthood, but a small group of persons—fewer than 20%—remain afflicted into their adult years.1,2
DOPAMINE MAY BE CAUSAL
Evidence collected by Harvey Singer, MD, of the Division of Pediatric Neurology at Johns Hopkins University School of Medicine in Baltimore, suggests that TS is caused by a defect involving the dopamine system and its effect on the corticostriatothalamocortical circuits.3,4
"Dopaminergic neurons directly influence cortical and striatal neurons as well as presynaptic glutamatergic corticostriatal terminals that synapse in the striatum. Whether dopamine's influence is inhibitory or excitatory depends on the type of receptors it interacts with," Singer explained.4 Dopamine can either depress or potentiate corticostriatal transmissions.5 Its effect on the resting potentials of striatal neurons could account for the waxing and waning pattern of tics noted in persons with TS.6
Most dopamine innervation to the cortex is in the frontal region, especially the striatum.7,8 Gilbert and colleagues9 report that the brain of adults with TS is structured differently from that of others in that it has fewer D2 receptors in extrastriatal regions. The TS-affected brain also has reduced distribution volume ratio values in the orbitofrontal and motor cortex, hippocampus, anterior cingulate gyrus, and mediodorsal thalamus, suggesting reduced D2 or D3 receptor density. In his view, the thalamus may play a crucial role in sensory, cognitive, limbic, and behavioral difficulties in TS.
Singer and his group also are studying the brain structure of patients with TS. In 1 study, the team performed a postmortem analysis of brain tissue to determine whether the defect might be located in the frontal lobe.10 "The frontal lobe is integral to the circuits that connect cortical regions to basal ganglia, and it is a site where tics and associated comorbidities could originate," explained Dustin Yoon, a teaching assistant at Johns Hopkins and the study's lead author.
The investigators analyzed tissue samples for several neurochemical markers: dopamine (D1, D2), serotonin (5HT-1A), a-adrenergic (a2A) receptors, dopamine transporter (DAT), and vesicular docking and release proteins.10 While the sample size was small—3 patients with TS and 3 matched controls—DAT and D2 receptor densities were consistently increased in 5 of 6 frontal regions in all the patients with TS. Density values for persons with TS versus controls ranged from 133% to 276% for DAT, and from 132% to 182% for the D2 receptor.10
"We found that the actual density of DAT and D2 exceeded 150% of control values. A lot of things can contribute to this. It may be that patients with TS have an intrinsic regulatory defect that causes receptor density to increase, or there may be frontal dopaminergic hyperinnervation from the ventral tegmental area," explained Yoon. But he and his colleagues cautioned that their findings must be considered within the context of the effect of medications on the brain. "Treatment with neuroleptics— including dopamine antagonists—increases D2 dopamine receptors in the striatum. It's entirely possible that our findings were the result of patients being treated chronically with neuroleptics," Yoon said.
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18. Tourette Syndrome Medical Advisory Board. Coffey B, Berlin C, Naarden A. Medications and Tourette's disorder: combined pharmacotherapy and drug interactions. Available at: www.tsa-usa.org/Medical/images/medications_and_
tourettes_berlin.pdf. Accessed July 13, 2007.
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