The study of neurotransmitter interactions using positron emission tomography and functional coupling

Functional brain imaging with positron emission tomography (PET) has opened up new avenues for the investigation of possible functional disturbances related to psychiatric disease as well as pharmacodynamic assessment of drug treatment in vivo. Different strategies to study pharmacologic 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 metabolism. Each of these can be performed either in a resting state or after perturbation with a pharmacologic challenge. Our group has developed a general strategy for investigating pharmacologic effects on brain function: (a) determining indirect drug-induced metabolic changes with fluorodeoxyglucose PET and (b) characterizing functional interactions of neurotransmitter systems by assaying drug-induced displacement of specific receptor ligands. These study designs reflect a paradigm shift where functional coupling of brain regions and interaction of different neurotransmitter systems are seen as the basis for a multitransmitter hypothesis of schizophrenia. In this view, any disturbance in the self-regulatory process is reflected in the loss of functional interaction between systems. An overview of recent studies and their possible clinical importance will be presented.