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D2-Like Dopamine Receptor Density in Tourette Syndrome Measured by PET

Department of Radiology, Division of Nuclear Medicine, Department of Neurology, Division of Pediatrie Neurology and Department of Psychiatry, The Johns Hopkins University School of Medicine, and Department of Environmental Health Sciences, Division of Radiation Health Sciences, and Department of Biostatistics, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland
Aarhus University PET Center, Aarhus, Denmark
Department of Epidemiology Aarhus,and Preventive Medicine, University of Maryland School of Medicine, Baltimore, Maryland

Correspondence: For correspondence or reprints: Dean F. Wong, MD, PhD, Department of Radiology, Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Johns Hopkins Outpatient Center, Research Wing, Room 3245, 601 N. Caroline St., Baltimore, MD 21287-0807.

ABSTRACT

Tourette syndrome (TS) is a chronic neurologic disorder characterized by the presence of involuntary motor and phonic tics. There is evidence that TS is associated with an abnormality of the dopami-nergic system, involving postsynaptic D2 receptors. We tested the hypothesis that D2-like dopamine receptors are elevated in TS. Methods: Twenty-nine adult patients with TS were studied by PET imaging with [¹¹C]3-N-methylspiperone ([¹¹C]NMSP). Two methods of data analysis were used. The first was a caudate-to-cerebellar ratio, measured at 45 min. The second method, applied in 20 subjects, was a two-PET scan procedure. Both used high specific activity [¹¹C]NMSP, but the second scan was preceded by a dose of unlabeled haloperidol, which partially occupied the D2-like dopamine receptors. This was done to provide an absolute measure of receptor density (B_max). All patients were compared to age-and sex-matched controls. Results: Neither group showed significant differences from their control group in caudate-to-cerebellar ratio. However, the two-PET scan B_max measurement demonstrated that 4 of the 20 patients had significantly elevated D2-like receptors. In this group of 20 patients, multiple linear regression analysis revealed a trend between the severity of vocal tics and B_max values. This B_max measure also revealed a significant (p <0.05) association with performance on the Wisconsin Card Sorting Test. Conclusion: These findings suggest that not all patients with TS have an abnormality of D2-like receptors, but a subgroup of TS subjects has a significant D2-like dopamine receptor elevation. These findings also support the importance of applying a more quantitative method for B_max determination to PET imaging analysis. The B_max findings in the subgroup do not exclude an effect of intrasynaptic dopamine competition, but this effect may be less likely due to the high affinity of [¹¹C]NMSP.

Key Words: PET • D2-like dopamine receptor density • Tourette syndrome • neuropsychology

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