RESUMO
BACKGROUND AND HYPOTHESIS: The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia. STUDY DESIGN: Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29). STUDY RESULTS: A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (râ =â 0.54, Pâ =â .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (râ =â 0.58, Pâ =â .02), general (râ =â 0.53, Pâ =â .04), and total symptom scores (râ =â 0.063, Pâ =â .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (râ =â 0.51, Pâ =â .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (râ =â 0.66, Pâ =â .005) and throughout all follow-up visits. CONCLUSIONS: These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.