title: Effect of sertraline on glucocorticoid sensitivity of mononuclear leukocytes in post-traumatic stress disorder.
abstract: This study examined the effects of sertraline (SER) on glucocorticoid sensitivity in mononuclear leukocytes (MNL) from eight subjects with current post-traumatic stress disorder (PTSD) and nine comparison subjects. In all, 60 ml of blood was withdrawn by venipuncture at 0800, and MNL were isolated from blood and divided into two portions: the first contained live cells incubated with a series of concentrations of dexamethasone (DEX); the second contained cells incubated with similar concentrations of DEX+2 muM SER. Group difference in the concentrations of DEX required to inhibit lysozyme activity by 50% were evaluated under conditions of DEX-only and DEX+SER using analysis of covariance (ANCOVA). A significant Group x Condition interaction reflected that SER altered the lysozyme IC(50-DEX) in the direction of decreasing sensitivity to glucocorticoids in PTSD while having no uniform effect in cells from comparison subjects. The data provide support for the idea that glucocorticoid receptors might be more responsive to antidepressants in PTSD than in persons without PTSD. Insofar as increased sensitivity to glucocorticoids has been linked with PTSD, the actions of SER on the lysozyme IC(50-DEX) suggest that this medication may target a biologic alteration associated with PTSD pathophysiology.
authors.affiliation: The Traumatic Stress Studies Program, Department of Psychiatry, Mount Sinai School of Medicine and the Bronx Veterans Affairs Medical Center, Bronx, NY, USA. Rachel.Yehuda@med.va.gov
authors.forename: Rachel
authors.initials: R
authors.lastname: Yehuda
authors.forename: Ren-Kui
authors.initials: RK
authors.lastname: Yang
authors.forename: Julia A
authors.initials: JA
authors.lastname: Golier
authors.forename: Robert A
authors.initials: RA
authors.lastname: Grossman
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bierer
authors.forename: Lisa
authors.initials: L
authors.lastname: Tischler
mesh_terms: D000328:Adult; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009113:Muramidase / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood*
chemical_list: D003907:Dexamethasone; D005938:Glucocorticoids; D006854:Hydrocortisone; D009113:Muramidase; D011965:Receptors, Glucocorticoid; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline