A preliminary report of an in vivo investigation of amphetamine-induced dopamine release in schizophrenia.

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) = [BP_saline - BP_amphetamine]/[BP_saline] 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)