THE STUDY OF NEUROTRANSMITTER INTERACTIONS USING POSITRON EMISSION TOMOGRAPHY AND FUNCTIONAL COUPLING

Functional brain imaging with positron emission tomography (PET) has o pened up new avenues for the investigation of possible functional dist urbances related to psychiatric disease as well as pharmacodynamic ass essment of drug treatment in vivo, Different strategies to study pharm acologic effects on the brain have been developed in recent years. The basic methods are to measure (a) blood flow or glucose metabolism, (b ) parameters of specific receptor binding, or (c) neurotransmitter met abolism. Each of these can be performed either in a resting state or a fter perturbation with a pharmacologic challenge. Our group has develo ped a general strategy for investigating pharmacologic effects on brai n function: (a) determining indirect drug-induced metabolic changes wi th fluorodeoxyglucose PET and (b) characterizing functional interactio ns of neurotransmitter systems by assaying drug-induced displacement o f specific receptor ligands. These study designs reflect a paradigm sh ift where functional coupling of brain regions and interaction of diff erent neurotransmitter systems are seen as the basis for a multitransm itter hypothesis of schizophrenia. In this view, any disturbance in th e self-regulatory process is reflected in the loss of functional inter action between systems, An overview of recent studies and their possib le clinical importance will be presented.