TY - JOUR
T1 - Comparison of in vivo and in vitro glucocorticoid sensitivity in depression
T2 - Relationship to the dexamethasone suppression test
AU - Lowy, Martin T.
AU - Reder, Anthony T.
AU - Gormley, Glenn J.
AU - Meltzer, Herbert Y.
N1 - Funding Information:
From the Department of Psychiatry, Case Western Reserve University, Cleveland, OH (M.T.L., H.Y.M.); the Department of Neurology, University of Chicago, ChiCagO, IL (A.T.R.); and the Department of Pediatrics. UCLA School of Medicine, Los Angeles, CA (G.J.G.). Supported in pat by NIMH Grants MH41683-01 and MH41684, National Institute on Aging Grant AGO1798, and the Kmc Foundation. M.T.L. ~8s supported by Training Grant T32 MH14651, and H.Y.M. is a recipient of Research C-r Scientist Award MH47808. A.T.R. is a Hmy Weaver Neuroscience Scholar (JI??027-A-1) and is support& NIH-CIDA 1 K08 NS01068-01. G.J.G. is a P&w Postdoctoral Fellow and is sqported by the MacArthur Poundedon. Address reprint reqUeStS to Dr. M. T. Logy, Department of Psychiatry, Case Western Reserve University, 2040 Abington Road. Cleveland, OH 44106. Received August 19, 1987; revised December 14, 1987.
PY - 1988/10
Y1 - 1988/10
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-3223(88)90136-9
DO - 10.1016/0006-3223(88)90136-9
M3 - Article
C2 - 3262379
AN - SCOPUS:0023766021
SN - 0006-3223
VL - 24
SP - 619
EP - 630
JO - Biological psychiatry
JF - Biological psychiatry
IS - 6
ER -