Modulation of limbic circuitry predicts treatment response to antipsychotic medication: a functional imaging study in schizophrenia

The regional neuronal changes taking place in the early and late stages of antipsychotic treatment are still not well characterized in humans. In addition, it is not known whether these regional changes are predictive or correlated with treatment response. Using PET with (15)O, we evaluated the time course of regional cerebral blood flow (rCBF) patterns generated by a first (haloperidol) and a second (olanzapine) generation antipsychotic drug (APD) in patients with schizophrenia during a 6 week treatment trial. Patients were initially scanned after withdrawal of all psychotropic medication (two weeks), and then blindly randomized to treatment with haloperidol (n=12) or olanzapine (n=17) for a period of 6 weeks. Patients were scanned again after 1 and 6 weeks of treatment. All assessments, including scanning sessions, were obtained in a double-blind manner. As hypothesized, we observed rCBF changes that were common to both drugs, implicating cortico-subcortical and limbic neuronal networks in antipsychotic action. In addition, in these regions, some patterns seen at week 1 and 6 were distinctive, indexing neuronal changes related to an early (ventral striatum, hippocampus) and consolidated [anterior cingulate/medial frontal cortex (ACC/MFC)] stage of drug response. Finally, both after 1 and 6 weeks of treatment, we observe differential patterns of rCBF activation between good and poor responders. After one week of treatment, greater rCBF increase in ventral striatum and greater decrease in hippocampus were associated with good response.