Since 1976 this project has emphasized dysregulation of the hypothalamo-pituitary-adrenal (HPA) neuroendocrine system in patients with melancholia or biological depression. The main focus was the dexamethasone suppression test (DST) - as a diagnostic aid, its association with other biological markers, its clinical correlates and its implications for a new nosology of clinical depressions. We have now shifted our emphasis to basic studies of HPA physiology and pathophysiology in normal humans and depressed patients. With our new, highly sensitive and specific assay for ACTH, we are studying the dynamic regulation of pituitary ACTH release by corticotropin releasing factor (CRF) and vasopressin under conditions of low glucocorticoid feedback (with RU 486) and high glucocorticoid feedback (with dexamethasone). The experiments are designed to clarify the functional status of ACTH-secreting anterior pituitary cells in depressed patients with abnormal DSTs and disinhibited HPA activity. The pituitary sensitivity to CRF and/or vasopressin under high and low feedback conditions will yield data relevant to the hypothesis of excessive CRF release through hypothalamic-limbic overdrive in depression. Other experiments will use gas chromatographic-mass spectrometric methods to study dexamethasone metabolism, single-dose pharmacokinetics, profile of metabolites, and immuno-cross-reactivity of metabolites in clinical radio- immunoassays for plasma dexamethasone. These studies will advance our understanding of normal HPA regulation and the pathophysiology of this system in depression. The results will lead to improved HPA assessment procedures, will suggest new approaches to the biological classification of depressions, and will likely suggest revisions of current concepts of the psychobiology of stress.
| Cassidy, F; Ritchie, J C; Carroll, B J (1998) Plasma dexamethasone concentration and cortisol response during manic episodes. Biol Psychiatry 43:747-54 |
| Krishnan, K R; Ritchie, J C; Manepalli, A N et al. (1991) Role of serotonin in hypothalamo pituitary adrenal axis escape from dexamethasone suppression. Prog Neuropsychopharmacol Biol Psychiatry 15:637-42 |
| Kayganich, K; Watson, J T; Kilts, C et al. (1990) Determination of plasma dexamethasone by chemical oxidation and electron capture negative ionization mass spectrometry. Biomed Environ Mass Spectrom 19:341-7 |
| Ritchie, J C; Belkin, B M; Krishnan, K R et al. (1990) Plasma dexamethasone concentrations and the dexamethasone suppression test. Biol Psychiatry 27:159-73 |
| Rao, V P; Krishnan, K R; Goli, V et al. (1989) Neuroanatomical changes and hypothalamo-pituitary-adrenal axis abnormalities. Biol Psychiatry 26:729-32 |
| Lee, M A; Flegel, P; Cameron, O G et al. (1988) Chronic caffeine consumption and the dexamethasone suppression test in depression. Psychiatry Res 24:61-5 |
| Lee, M A; Flegel, P; Greden, J F et al. (1988) Anxiogenic effects of caffeine on panic and depressed patients. Am J Psychiatry 145:632-5 |
| Cameron, O G; Thomas, B; Tiongco, D et al. (1987) Hypercortisolism in diabetes mellitus. Diabetes Care 10:662-4 |
| Grunhaus, L; Zelnik, T; Albala, A A et al. (1987) Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy. J Affect Disord 13:233-40 |
| Kumar, A; Shipley, J E; Eiser, A S et al. (1987) Clinical correlates of sleep onset REM periods in depression. Biol Psychiatry 22:1477-81 |
Showing the most recent 10 out of 12 publications
