Applications of neuroreceptor imaging to psychiatry research

Over the past two decades, there have been significant advances in the ability to study the neurochemistry of the living brain using neuroreceptor radiotracers with Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging modalities. The greater availability of radiotracers for neurotransmitter synthesis/metabolism, enzymes, transporters and receptors, as well as neuromodulators and second messengers has enabled the evaluation of hypotheses regarding neurotransmitter function and regulation that are generated from basic neuroscience studies in animals, and the investigation of the neurochemical substrates of psychiatric disorders and the mechanism of action of psychotropic medications. This review will focus on the status of radiotracer development, on the clinical and methodological considerations regarding neurochemical brain imaging study design and data interpretation. The applications of neurochemical brain imaging methods to the study of specific psychiatric disorders, including schizophrenia, anxiety disorders, depression and Alzheimer's Disease, will be reviewed and potential future directions of research in these areas identified. Finally, the studies of the neurochemical substrates of personality traits will be reviewed. Thus far, fundamental observations have been made with respect to 1). detecting abnormalities in the availability of neurotransmitter transporter and receptor sites in psychiatric patients; 2). evaluating the relationship of these neurochemical measures to symptomatology; and 3). assessing the magnitude of occupancy of the initial target sites of action of psychotropic medication relative to treatment response and drug concentrations. Further advances in instrumentation and radiotracer chemistry will enable investigators to conduct pre-clinical and clinical mechanistic studies focused on other neurotransmitters and neuromodulators. These data will provide important insights into the neurochemical substrates of treatment response variability in psychiatric disorders that will have important implications for the refinement of pharmacotherapy.