title: Vasoconstrictor response to topical beclomethasone in major depression.
abstract: Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been frequently described in depression. Due to the closed-loop nature of the HPA axis, one possible cause of this overactivity may be a defect in negative feedback regulation, in particular an abnormality of the glucocorticoid receptor (GR). In the present study, the vasoconstrictor response to the topical glucocorticoid, beclomethasone, was used to examine GR function in depression. Topical beclomethasone was applied in four concentrations (10 microl each of 3, 10, 30 and 100 microg/ml) to the forearms of 22 subjects with major depression and their age- and sex-matched controls. Skin blanching responses were compared between the depressed and control groups and, within the depressed group, on the basis of the modified dexamethasone suppression test (DST), between cortisol suppressors and non-suppressors. Depressed subjects demonstrated a significantly reduced vasoconstrictor response compared to controls (P=0.0001). No difference was detected between cortisol suppressors and non-suppressors in their skin blanching responses. These findings suggest that peripheral GR function is abnormal in depression but that the reduced vasoconstrictor response to beclomethasone is not necessarily a secondary effect of hypercortisolaemia or HPA axis overactivity.
authors.affiliation: Section of Metabolic Studies, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. paul.cotter@dhh.n-i.nhs.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Cotter
authors.forename: Owen F
authors.initials: OF
authors.lastname: Mulligan
authors.forename: Sabine
authors.initials: S
authors.lastname: Landau
authors.forename: Andrew
authors.initials: A
authors.lastname: Papadopoulos
authors.forename: Stafford L
authors.initials: SL
authors.lastname: Lightman
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Checkley
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D001507:Beclomethasone; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005246:Feedback / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D011965:Receptors, Glucocorticoid; D001507:Beclomethasone; D006854:Hydrocortisone