Assessment of striatal dopamine function in schizophrenia

The dopamine hypothesis states that schizophrenia is caused by dysregulated dopamine function. Although this hypothesis has stood as the primary pathophysiologic hypothesis for this illness for over two decades, conclusive evidence confirming or refuting it has been lacking. To directly test this hypothesis, we developed a method to quantify synaptic dopamine concentrations in vivo by determining changes in 11-C-raclopride striatal binding with PET after administration of the dopamine agonist amphetamine. Fifty minutes after a bolus/constant infusion of 11-C-raclopride (8 miC) and equilibrium is reached, amphetamine (.2mg/kg) is infused over one minute. Scanning continues for 50 minutes after amphetamine administration. Pre versus post amphetamine striatal binding is determined using V-3 ratios (striatum - cerebellum/cerebellum). To date, 10 healthy controls, 4 neuroleptic-naive and 8 neuroleptic-free patients with schizophrenia or schizoaffective disorder have participated in the study. Preliminary analyses suggest that both groups had significant reductions in post-amphetamine 11-C-raclopride striatal binding concentrations (i.e., increased synaptic dopamine levels) and that the patients had greater range and different patterns of striatal binding compared to controls. The entire data set will be presented.