It has been suggested that biogenic amine dysfunction in affective illness and schizophrenia may be the result of alterations in the monoamine receptor sensitivity in the central nervous system of these patients. Although some evidence to support this suggestion is provided by animal studies, evidence from human studies has been lacking. Recently two preliminary studies of beta-adrenergic receptor sensitivity conclude that such alterations in monoamine receptor function exist in the leukocytes of depressed patients. This project examines the role of monoamine receptors in the etiology of psychiatric illness and the relationship between therapeutic response to psychotropic drugs and alterations in monoamine receptor sensitivity. The monoamine receptors studied in peripheral tissue of these schizophrenic, depressed, and manic patients and normal controls are (1) alpha-adrenergic (Alpha-2) and serotonin 1 & 2 receptors and (2) beta adrenergic and histamine-2 receptors in leukocytes. The receptor sensitivity will be examined (1) by determining alterations in 3H-cyclic AMP accumulation as a result of stimulation of these receptors and/or (2) by determining the kinetic characteristics of these receptors with radio labelled ligand binding techniques (maximum number of binding sites, disassociation constant). The first part of the project will compare characteristics of these receptors among different diagnostic (e.g., subgroups DSM III schizophrenics, schizophreniform psychosis cluster, unipolar depression, bipolar-depression, bipolar mania), and normal controls to determine if alterations in one or more of the monoamine receptor sensitivity are associated with one or several of these diagnostic subgroups. The second part of the project will examine if treatment with psychotropic drugs causes changes in monoamine receptor sensitivity and whether or not such changes are related to clinical response to these drugs. The project is intended to examine the proposed hypothesis that alterations in monoamine receptor sensitivity may be associated with at least some forms of affective illness and schizophrenia.
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