Studies in the last four years have yielded empirical observations that have added substantially to the body of literature on EEG sleep characteristics in affective states. A data base now exists which demonstrates changes in the sleep of patients receiving different tricyclic antidepressants, the relationship of such changes to clinical response, and the characteristics of an eight-hour window combined sleep/neuroendocrine observations. The continued development and application of automated and computerized techniques for """"""""microanalysis"""""""" of sleep variables, the availability of antidepressant plasma levels and accurate assays for selected neuroendocrine measures, recent advances in the neuropeptide field, and the expanding capability of conducting both intensive investigations and field studies now make it possible to take the next logical steps of continuing our inquiries on EEG sleep in relation to affective illness. In the coming grant period, we would like to expand our inquiries by: (1) examining the immediate effects of antidepressants that appear to act specifically on neuronal serotonergic uptake (fluvoxamine versus amitriptyline) on the sleep of nondelusional depressed patients; (2) conducting a similar type of investigation comparing intravenous chlorimipramine (specific action on serotonergic uptake) to oral chlorimipramine (greater action on adrenergic reuptake systems); (3) extending our investigations of neuroendocrine regulation by studying the effects of growth hormone releasing factor (GRF) and somatostatin (SRIF) on the sleep of depressed patients, normals and animals; (4) using these strategies to focus intensively on the first 100 minutes following sleep onset--especially the first NREM-REM sleep cycle--by instituting a pharmacologic tricyclic probe and assessing changes that occur with respect to sleep, neuroendocrine, and temperature rhythms; (5) examining the hypothesized """"""""specificity"""""""" of psychobiological measures in delusional depression with automated sleep analyses; (6) examining with automated analyses the extent of the sleep changes that accompany aging in both normal individuals and depressed patients of both genders between ages 18-80 in a total sample of 360 individuals; and (7) conducting neurophysiological investigations of pregnant women with a history of depression and of their offspring during early development.
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