1630 Objectives To characterize the effects of amphetamine on dopaminergic neurotransmission in schizophrenia. Methods Participants with schizophrenia (N=17) (5F, 12M) and [healthy participants (N=21) (8F, 13M)], aged in years, mean = 32.94 [31.33], range = (18, 48) [(18,53)], underwent two 90-min PET scans after intravenous (IV) injections of 740 Mbq (20 mCi) high-specific-activity [11C]raclopride. Five min before the first scan, they received 10 mL 0.9% NaCl intravenously (IV) (inert), and five min before the second scan, they received 0.3 mg/kg amphetamine IV (challenge). Dopamine release was calculated by means of true equilibrium bolus estimation (TREMBLE) (Wong, et al, 1998) utilizing regions of interest (ROIs) manually drawn on coregistered images of PET and MRI as follows: caudate nucleus (CN), putamen (P), and ventral striatum (VS). Dopamine release (DAR) = [BPsaline - BPamphetamine]/[BPsaline] where BP = binding potential Results DAR in CN, P, and VS did not differentiate people with established schizophrenia (N=9) (1F, 8M) from [healthy participants (N=9) (5F, 4M)]. In contrast, a never-medicated subject suffering a first psychotic episode (a 29-year-old man, see Table) demonstrated substantial dopamine release of 0.29 CN, 0.31 P, and 0.32 VS, values far exceeding those for participants with the syndrome of Gilles de la Tourette and healthy participants (Wong, et al, 2008). Conclusions People with initial psychotic symptoms of schizophrenia without medication may exhibit marked phasic elevations of both psychotic symptoms and striatal DAR. Research Support PHS Grants RO1 MH078175, NS38927, K24 DA00412, RO1 AA12839, the Johns Hopkins Institute for Clinical and Translational Research (ICTR) Grant Number UL1 TR 001079 from the Center for Advancing Translational Sciences (NCATS), a component of NIH and NIH roadmap for Medical Research, and the Brain and Behavior Research Foundation (NARSAD)

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) (< 3 micrograms) [11C]raclopride and (B) again four or more days later after the intravenous injection of 740 MBq (20 mCi) low-specific-activity (LSA) (< 600 micrograms) [11C]raclopride. We defined dopamine receptor occupancy = BPHSA - BPLSA ---------------------------- 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.

Two radioligands specific for the dopamine system were used to study the influence of correction for partial volume effects on quantitative binding data obtained from positron emission tomography from various brain regions. [11C]Raclopride binds to the dopamine D2 and D3 receptors, and [11C]WIN 35,428 binds to the dopamine transporter. Both are highly concentrated in the basal ganglia but not in the cerebellum. Normal subjects and patients with Lesch-Nyhan syndrome, a disease in which brain atrophy occurs, were studied before and after correction for the partial volume effect. A dramatic elevation in rate constants, especially the k3/k4 ratio, was observed after correction in both normal subjects and patients. The patients, who initially had a decrease in [11C]WIN 35,428 binding at the dopamine transporter site compared to normal subjects, retained this separation after the correction algorithm was applied.