Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: relationship to the dexamethasone suppression test.
The effect of in vivo (1 mg) and in vitro (10(-7)-10(-10) M) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 AM and 4:00 PM. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10(-9)-10(-10) M), nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 PM cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.
Lowy
M T
MT
Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106.
Reder
A T
AT
Gormley
G J
GJ
Meltzer
H Y
HY
D000328:Adult; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003208:Concanavalin A / Q000276:immunology; D003866:Depressive Disorder / Q000175:diagnosis* / Q000276:immunology; D003907:Dexamethasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000276:immunology; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects
D010835:Phytohemagglutinins; D011965:Receptors, Glucocorticoid; D003208:Concanavalin A; D003907:Dexamethasone; D006854:Hydrocortisone