Immediate effects of risperidone on cortico-striato-thalamic loops and thehippocampus

Background Functional imaging studies indicate that delusions and hallucina tions in schizophrenia are associated with overactivity of the left hippoca mpus and ventral striatum. Hippocampal neuronal firing modulates feedback t o cortex via cortico - striato - thalamic loops. Aims To test the hypothesis that recovery from psychosis is associated with decrease in activity in cortico-striato-thalamic circuits, and. furthermor e, that reduction in hippocampal activity predicts the degree of alleviatio n of delusions and hallucinations. Method Positron emission tomography (PET) was used to measure the effects o f the atypical antipsychotic, risperidone, on glucose metabolism in eight f irst-episode schizophrenia patients. Results A single dose of risperidone produced decreases in metabolism in ve ntral striatum, thalamus and frontal cortex. The magnitude of decreases in left hippocampus predicted subsequent reduction in delusions and hallucinat ions. After six weeks' treatment with risperidone, the decreases in frontal metabolism were more extensive. Conclusions The mechanism of antipsychotic action of risperidone entails re duction of hippocampal activity together with reduced feedback via cortico- striato-thalamic loops. Declaration of interest Supported in part by the Norma Calder Foundation.