Effects of dexamethasone on declarative memory function in posttraumatic stress disorder J. Douglas Bremner a,b, * , Meena Vythilingam c , Eric Vermetten d , Nadeem Afzal a,b , Ahsan Nazeer a,b , John W. Newcomer e , Dennis S. Charney c a Departments of Psychiatry and Behavioral Sciences and Radiology, Emory Center for Positron Emission Tomography, Emory University School of Medicine, Atlanta 30306 GA, USA b Atlanta VAMC, Decatur, GA, USA c Program for Mood and Anxiety Disorders, National Institute of Mental Health, Bethesda, MD, USA d Department of Psychiatry, Central Military Hospital and University Medical Center, Utrecht, The Netherlands e Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Received 13 February 2004; received in revised form 4 August 2004; accepted 14 August 2004 Abstract Alterations in the hypothalamic–pituitary–adrenal (HPA) axis and hippocampal-based memory have been associated with posttraumatic stress disorder (PTSD), and the administration of exogenous glucocorticoids has been shown to result in a transient verbal declarative memory impairment in healthy human subjects. The purpose of this study was to assess the effects of the glucocorticoid dexamethasone on verbal declarative memory function in patients with PTSD. Forty-two men and women with (n =14) and without (n =28) PTSD received placebo or dexamethasone (1 and 2 mg on two successive days) in a double- blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall related to a relative detrimental effect of dexamethasone on memory function in healthy subjects, but not those with PTSD. These findings are consistent with an altered sensitivity of declarative memory function in PTSD to regulation by glucocorticoids, possibly explainable by alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: PTSD; Memory; Dexamethasone; Cortisol; Glucocorticoids; Hippocampus 1. Introduction Alterations in cognition and memory are an important aspect of the clinical presentation of posttraumatic stress disorder (PTSD). Empirical stud- 0165-1781/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2004.08.004 * Corresponding author. Department of Psychiatry and Behav- ioral Sciences, Emory University, 1256 Briarcliff Road, Atlanta, GA 30306, USA. Tel.: +1 404 727-4193; fax: +1 404 712 8442. E-mail address: jdbremn@emory.edu (J.D. Bremner). Psychiatry Research 129 (2004) 1 – 10 www.elsevier.com/locate/psychres