Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations, as shown by a novel positron emission tomography (PET) method. This study used nonhuman primates and patients with schizophrenia to examine the relationship between amphetamine-induced changes in striatal extracellular dopamine levels and changes in [¹¹C]raclopride binding, a radioligand that binds to dopamine D2/D3 receptors. In nonhuman primates, doubling the amphetamine dose resulted in a doubling of [¹¹C]raclopride specific binding reductions, indicating a strong correlation between dopamine levels and binding changes. The ratio of percent mean dopamine increase to percent mean striatal binding reduction was 44:1 for 0.2 mg/kg amphetamine, showing that small binding changes reflect large dopamine outflow changes. In the clinical study, patients with schizophrenia showed significantly greater amphetamine-related reductions in [¹¹C]raclopride specific binding compared to healthy controls (mean -22.3% vs. -15.5%). This suggests that schizophrenia patients have substantially higher synaptic dopamine concentrations than controls. These findings support the hypothesis that schizophrenia is associated with increased psychostimulant-induced synaptic dopamine concentrations. The study also found that amphetamine-induced changes in dopamine levels were correlated with changes in behavioral symptoms, as measured by the Brief Psychiatric Rating Scale (BPRS). Patients with schizophrenia showed greater increases in BPRS total scores and psychosis subfactor scores compared to controls, indicating a relationship between dopamine levels and symptom severity. The study used a novel brain imaging technique to measure in vivo synaptic dopamine concentrations by quantifying changes in [¹¹C]raclopride binding. This method provides an indirect measure of dopamine levels by assessing the competition between synaptic dopamine and the radiotracer for receptor binding. The results suggest that schizophrenia patients have greater dopamine outflow than controls, which may contribute to the symptoms of the disorder. The study also found that previous neuroleptic treatment did not significantly affect the binding differences between schizophrenia patients and controls. These findings support the hypothesis that schizophrenia is associated with increased dopamine activity, which may be a key factor in the pathophysiology of the disorder.Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations, as shown by a novel positron emission tomography (PET) method. This study used nonhuman primates and patients with schizophrenia to examine the relationship between amphetamine-induced changes in striatal extracellular dopamine levels and changes in [¹¹C]raclopride binding, a radioligand that binds to dopamine D2/D3 receptors. In nonhuman primates, doubling the amphetamine dose resulted in a doubling of [¹¹C]raclopride specific binding reductions, indicating a strong correlation between dopamine levels and binding changes. The ratio of percent mean dopamine increase to percent mean striatal binding reduction was 44:1 for 0.2 mg/kg amphetamine, showing that small binding changes reflect large dopamine outflow changes. In the clinical study, patients with schizophrenia showed significantly greater amphetamine-related reductions in [¹¹C]raclopride specific binding compared to healthy controls (mean -22.3% vs. -15.5%). This suggests that schizophrenia patients have substantially higher synaptic dopamine concentrations than controls. These findings support the hypothesis that schizophrenia is associated with increased psychostimulant-induced synaptic dopamine concentrations. The study also found that amphetamine-induced changes in dopamine levels were correlated with changes in behavioral symptoms, as measured by the Brief Psychiatric Rating Scale (BPRS). Patients with schizophrenia showed greater increases in BPRS total scores and psychosis subfactor scores compared to controls, indicating a relationship between dopamine levels and symptom severity. The study used a novel brain imaging technique to measure in vivo synaptic dopamine concentrations by quantifying changes in [¹¹C]raclopride binding. This method provides an indirect measure of dopamine levels by assessing the competition between synaptic dopamine and the radiotracer for receptor binding. The results suggest that schizophrenia patients have greater dopamine outflow than controls, which may contribute to the symptoms of the disorder. The study also found that previous neuroleptic treatment did not significantly affect the binding differences between schizophrenia patients and controls. These findings support the hypothesis that schizophrenia is associated with increased dopamine activity, which may be a key factor in the pathophysiology of the disorder.