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Striatal [¹¹C]dihydrotetrabenazine and [¹¹C]methylphenidate binding in Tourette syndrome

From the Geriatrics Research, Education, and Clinical Center (R.L.A.), Ann Arbor VAMC; Departments of Neurology (R.L.A., K.W., K.A.F.) and Radiology (Division of Nuclear Medicine) (R.A.K., K.W., M.R.K., K.A.F.), University of Michigan Medical School, Ann Arbor; Department of Biostatistics (W.Z., T.N.), School of Public Health, University of Michigan, Ann Arbor; and GlaxoSmithKline Clinical Imaging Centre (T.N.), Imperial College, London, UK.

Address correspondence and reprint requests to Dr. Roger L. Albin, 5023 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 ralbin{at}umich.edu

Objective: Tourette syndrome (TS) is a common neurodevelopmental disorder marked by tics and behavioral comorbidities. Clinical pharmacology suggests that dopaminergic signaling abnormalities are part of the pathophysiology of TS. Prior molecular imaging studies of nigrostriatal dopaminergic terminal markers report conflicting results. Our goal was to characterize the distribution of nigrostriatal dopaminergic terminals in subjects with TS.

Methods: Thirty-three adult subjects with TS were studied with PET using [¹¹C]dihydrotetrabenazine (DTBZ), a ligand for the type 2 vesicular monoamine transporter, and with [¹¹C] methylphenidate (MP), a ligand for the plasmalemmal dopamine transporter. Subjects were characterized with standard rating instruments for tic severity, obsessive-compulsive behaviors, and attentional deficits.

Results: We found no differences between subjects with TS and control subjects in DTBZ and MP binding in any striatal region. There was no correlation between binding measures and clinical variables. Ventral striatal DTBZ and MP binding distributions in subjects with TS were normal.

Conclusions: We found no evidence of increased striatal dopaminergic innervation in Tourette syndrome (TS). Discrepancy between our present results and those of other studies may be explained by heterogeneity of TS.

Abbreviations: BP = binding potential; CAARS-S:S = Conners Adult ADHD Rating Scale-Self Report: Short version; DAT = dopamine transporter; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; DTBZ = [¹¹C]dihydrotetrabenazine; DVR = ratio of volumes of distribution; FDR = false discovery rate; MP = [¹¹C]methylphenidate; OCBs = obsessive-compulsive behaviors; TS = Tourette syndrome; VOI = volume of interest; YBOCS = Yale-Brown Obsessive Compulsive Scale; YGTSS = Yale Global Tic Severity Scale.

Supplemental data at www.neurology.org

Supported by NS15655, UL1RR024986, and a VA Merit Review Grant (R.L.A.).

Disclosure: The authors report no disclosures.

Received September 18, 2008. Accepted in final form January 13, 2009.