Immediate effects of risperidone on cortico-striato-thalamic loops and the hippocampus.

Abstract

Functional imaging studies indicate that delusions and hallucinations in schizophrenia are associated with overactivity of the left hippocampus and ventral striatum. Hippocampal neuronal firing modulates feedback to cortex via cortico-striato-thalamic loops. To test the hypothesis that recovery from psychosis is associated with decrease in activity in cortico-striato-thalamic circuits, and, furthermore, that reduction in hippocampal activity predicts the degree of alleviation of delusions and hallucinations. Positron emission tomography (PET) was used to measure the effects of the atypical antipsychotic, risperidone, on glucose metabolism in eight first-episode schizophrenia patients. A single dose of risperidone produced decreases in metabolism in ventral striatum, thalamus and frontal cortex. The magnitude of decreases in left hippocampus predicted subsequent reduction in delusions and hallucinations. After six weeks' treatment with risperidone, the decreases in frontal metabolism were more extensive. The mechanism of antipsychotic action of risperidone entails reduction of hippocampal activity together with reduced feedback via cortico-striato-thalamic loops.