Increased Dopamine Receptor Occupancy in People with Tourette Syndrome, Obsessive-Compulsive Disorder, and Neuroleptic Exposure (P4.067)

OBJECTIVE: To compare and contrast the response to dopamine receptor blocking drugs in participants with and without Gilles de la Tourette syndrome (TS) and obsessive-compulsive disorder (OCD). BACKGROUND: Chronic pharmacological doses of dopamine D2/D3 receptor blocking drugs upregulate dopamine D2/D3 receptors. We hypothesized that dopamine D2/D3 receptor blocking drugs upregulate striatal dopamine D2/D3 receptors in patients with TS to a greater degree than patients with OCD and normal controls (Brasic, et al., 2013). To test this hypothesis, we sought to determine if dopamine D2/D3 receptor occupancy differentiates participants with TS and OCD from healthy controls. DESIGN/METHODS: Twenty-one adults (6 controls, 2 TS, 2 OCD, and 11 TS+OCD) underwent positron emission tomography (PET) for 90 minutes (A) after the intravenous injection of 740 MBq (20 mCi) high-specific-activity (HSA) ( 11 C]raclopride and (B) again four or more days later after the intravenous injection of 740 MBq (20 mCi) low-specific-activity (LSA) ( 11 C]raclopride. We defined dopamine receptor occupancy = BP HSA - BP LSA ---------------------------- BP HSA where BP = binding potential, HSA = high specific activity, and LSA = low specific activity, in the five subdivisions of the striatum: anterior and posterior caudate nucleus, anterior and posterior putamen, and ventral striatum. RESULTS: The dopamine receptor occupancy was significantly (P < 0.05) greater in patients with TS+OCD than in controls for all brain regions except the posterior caudate nucleus. CONCLUSIONS: Patients with TS+OCD experience a greater occupancy of striatal dopamine D2/D3 receptors after a pharmacological dose of a dopamine receptor blocking drug than normal controls. This finding may explain the limited efficacy of neuroleptics alone in many patients with TS+OCD. Study Supported by: National Institutes of Health (NIH): MH078175, NS38927, K24 DA00412, RO1 AA12839; National Center for Advancing Translational Science (NCATS): UL1RR025005; Tourette Syndrome Association, Inc.; Brain & Behavior Research Foundation (NARSAD); and the Essel Foundation. Disclosure: Dr. Brasic has nothing to disclose. Dr. Singer has received personal compensation in an editorial capacity for The Neurologist. Dr. Singer has received research support from Psyadon Pharmaceuticals. Dr. Zaidi has nothing to disclose. Dr. Gean has nothing to disclose. Dr. Kumar has nothing to disclose. Dr. Mathur has nothing to disclose. Dr. Mellinger-Pilgrim has nothing to disclose. Dr. Raymont has nothing to disclose. Dr. Dogan has nothing to disclose. Dr. Alexander has nothing to disclose. Dr. Maris has nothing to disclose. Dr. Nestadt has nothing to disclose. Dr. Gjedde has nothing to disclose. Dr. Wong has nothing to disclose.