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In vivo functional brain imaging, including global blood flow, regional cerebral blood flow (rCBF), measured with positron emission tomography (PET) and single photon emission computed tomography (SPECT), and regional cerebral metabolic rate (rCMR) measured with deoxyglucose PET, have been widely used in studies of psychiatric disorders. These studies have found modest differences and required large numbers of patients. Activation studies using rCBF or rCMR as indices of neuronal activity are more sensitive because patients act as their own control; however, findings localize regions of change but provide no data about specific neurotransmitter systems. After a general discussion of the role of neurotransmitter systems in neuropsychiatric disorders, an overview of the methodology of development and selection of radioligands for PET and SPECT is presented. Studies involving PET and SPECT ligand methods are reviewed and their findings summarized, including recent work demonstrating successive mutual modulation of neurotransmitter systems. Kinetic and equilibrium analysis modeling are reviewed. The emerging methodology of measuring neurotransmitter release on activation, both pharmacologically and by task performance, using ligand methods is reviewed and proposed as a promising new approach for studying psychiatric disorders.

In Vivo Imaging of Neurotransmitter Systems Using Radiolabeled Receptor Ligands