Increased Striatal Dopamine Transmission in Schizophrenia: Confirmation in a Second Cohort

OBJECTIVE: The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects. METHOD: Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D₂ receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D₂ receptor availability was measured with single photon emission computed tomography and the D₂ receptor radiotracer [¹²³I]IBZM. RESULTS: No differences were observed between patients with schizophrenia and the comparison group in D₂ receptor availability at baseline. Patients with schizophrenia exhibited a significantly larger reduction in D₂ receptor availability following acute amphetamine challenge than the comparison group. In this study, the effect size was smaller than in the first study. Excess dopamine release following amphetamine was associated with transient emergence or worsening of positive symptoms. CONCLUSIONS: In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia.