Neuropharmacological studies with SPECT in neuropsychiatric disorders

The last decade saw a rapid development of single photon emission computed tomography (SPECT) from a tool to assess cerebral blood flow to the study of specific neurotransmitter systems. Because of the relatively long half-life of SPECT radioisotopes, it is practical to measure the availability of neuroreceptors and transporters in conditions approaching equilibrium. The cost-efficiency of SPECT allowed studies in relatively large samples of patients with various neuropsychiatric disorders. We have applied this approach in studies of dopaminergic, serotonergic, and muscarinergic neurotransmission in patients with dementia, extrapyramidal disorders, schizophrenia, and alcoholism. No simple associations were observed between a single defect in one neurotransmitter system and a certain neuropsychiatric disease. Instead, complex dysfunction of several neurotransmitter systems in multiple, partially connected brain circuits have been implicated. Treatment effects also have been characterized. Microdialysis and neurotransmitter depletion studies showed that most radioligands and endogenous neurotransmitters compete for binding at receptors and transporters. Future research directions include the assessment of endogenous neurotransmitter concentrations measured by depletion studies and of genetic effects on neuroreceptor and transporter expression.