¹The Traumatic Stress Studies Program, Department of Psychiatry, Mount Sinai School of Medicine and the Bronx Veterans Affairs Medical Center, Bronx, NY, USA

Correspondence: Dr R Yehuda, Psychiatry 116A, Bronx Veterans Affairs, 130 West Kingsbridge Road, Bronx, NY 10468, USA, Tel: +1 718 584 9000 ext. 6964; Fax: +1 718 741 4775; E-mail: Rachel.Yehuda@med.va.gov

Received 12 January 2005; Revised 18 May 2005; Accepted 6 June 2005; Published online 10 August 2005.

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 In all, 60 ml of blood was withdrawn by venipuncture at 0800, and MNL were isolated from blood and divided into two portions: the first contained live cells incubated with a series of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 M 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 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.