Immediate effects of risperidone on cerebral activity in healthy subjects: a comparison with subjects with first-episode schizophrenia.

OBJECTIVE To test the hypothesis that administration of risperidone to healthy subjects produces reductions in metabolism in the frontal cortex similar to those produced by administration of risperidone to patients experiencing a first episode of schizophrenia. METHODS Positron emission tomography was used to measure the changes in regional metabolism produced by a single 2-mg dose of risperidone and by placebo, administered under randomized, double-blind conditions, in 9 healthy subjects. Conjunction analysis was used to identify those cerebral sites where changes in metabolism in the healthy subjects coincided with similar changes in metabolism observed in patients with schizophrenia. RESULTS Compared with placebo, risperidone produced reductions in metabolism in the left lateral frontal cortex and right medial frontal cortex in healthy subjects. Conjunction analysis revealed that these changes occurred at locations similar to the loci of change produced by risperidone in patients with schizophrenia. CONCLUSION Because the reduction in metabolism in the medial frontal cortex produced by risperidone is associated with alleviation of positive symptoms in patients with schizophrenia, the observation of a reduction in metabolism at a similar site in healthy subjects supports the hypothesis that the antipsychotic effect of risperidone arises, at least in part, from a physiologic effect that occurs in both patients with schizophrenia and healthy subjects.