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Dexamethasone, Glucocorticoid receptor, Major depression, Gene expression, DST, Dex-CRH test
Abstract:
Glucocorticoid challenge tests such as the dexamethasone suppression
test (DST) and the combined dexamethasone/corticotropin-releasing
hormone (dex-CRH) test are considered to be able to sensitively measure
hypothalamic-pituitary-adrenal (HPA) axis activity in stress-related
psychiatric and endocrine disorders. We used mass-spectrometry to assess
the relationship of plasma dexamethasone concentrations and the outcome
of these tests in two independent cohorts.
Dexamethasone concentrations were measured after oral ingestion of 1.5
mg dexamethasone in two cohorts that underwent a standard (dexamethasone
at 23:00 h) as well as modified (18:00 h) DST and dex-CRH test. The
first study population was a case/control cohort of 105 depressed
patients and 133 controls in which peripheral blood mRNA expression was
also measured. The second was a cohort of 261 depressed patients that
underwent a standard dex-CRH test at baseline and after 12 weeks'
treatment with cognitive-behavioral therapy or antidepressants.
Dexamethasone concentrations explained significant proportions of the
variance in the DST in both the first (24.6%) and the second (5.2%)
cohort. Dexamethasone concentrations explained a higher proportion of
the variance in the dex-CRH test readouts, with 41.9% of the cortisol
area under the curve (AUC) in the first sample and 24.7% in the second
sample. In contrast to these strong effects at later time points,
dexamethasone concentrations did not impact cortisol or ACTH
concentrations or mRNA expression 3 hours after ingestion. In the second
sample, dexamethasone concentrations at baseline and week 12 were highly
correlated, independent of treatment type and response status.
Importantly, a case/control effect in the Dex-CRH test was only apparent
when controlling for dexamethasone concentrations.
Our results suggest that the incorporation of plasma dexamethasone
concentration or measures of earlier endocrine read-outs may help to
improve the assessment of endocrine dysfunction in depression. (C) 2016
Elsevier Ltd. All rights reserved.
