Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia

Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using 18FN-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of 18FN-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS.