Estrogen Levels Are Associated with Extinction Deficits in Women with Posttraumatic Stress Disorder

• Type of Material: Article
• Authors: Ebony M. Glover, Emory University; Tanja Jovanovic, Emory University; Kristina B. Mercer, Emory University; Kimberly Kerley, Emory University; Bekh Bradley-Davino, Emory University; Kerry Ressler, Emory University; Seth Davin Norrholm, Emory University
• Language: English
• Date: 2012-07-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Society of Biological Psychiatry
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biopsych.2012.02.031
• Title of Journal or Parent Work: Biological Psychiatry
• ISSN: 0006-3223
• Volume: 72
• Issue: 1
• Start Page: 19
• End Page: 24
• Grant/Funding Information: This research was supported by National Institute of Mental Health Grant Nos. MH071537 (principal investigator KJR), and MH070129 (principal investigator TJ), the Howard Hughes Medical Institute (KJR), and the Atlanta Clinical Translational Science Institute, the National Institutes of Health National Centers for Research Resources (Grant No. M01 RR00039), and the Burroughs Wellcome Fund. This work was funded in part by Institutional Research and Academic Career Development Awards Grant No. K12–GM000680 (EMG), National Alliance for Research on Schizophrenia and Depression (TJ and SDN), and Department of Defense/Congressionally Directed Medical Research Program(Award No. W81XWH-08-2-0170; principal investigator SDN).
• Keywords: PTSD; Anxiety disorders; estrogen; fear extinction; fear-potentiated startle; trauma
• Research Categories: Psychology, General

Abstract

Background Women are twice as likely to develop posttraumatic stress disorder (PTSD) than men. As shown in our previous work, the inability to suppress fear responses in safe conditions may be a biomarker for PTSD. Low estrogen in naturally cycling women is associated with deficits in fear extinction. On the basis of these findings, we have now examined the influence of estrogen levels on fear extinction in women with and without PTSD. Methods We measured fear-potentiated startle during fear conditioning and extinction in women. The study sample (N = 81) was recruited from an urban, highly traumatized civilian population at Grady Memorial Hospital in Atlanta, Georgia. We assayed serum estrogen levels and used a median split to divide the sample into high and low estradiol (E2) groups. Seventeen of 41 women (41.5%) in the low E2 group and 15 of 40 women (37.5%) met criteria for PTSD in the high E2 group. Results The results showed that all groups had equivalent levels of fear conditioning. However, we found significant interaction effects between high versus low E2 groups and PTSD diagnosis [F(1,71) = 4.55, p < .05] on extinction. Among women with low estrogen levels, fear-potentiated startle was higher during extinction in the PTSD group compared with traumatized control women [F(1,38) = 5.04, p < .05]. This effect was absent in the High E2 group. Conclusion This study suggests that low estrogen may be a vulnerability factor for development of PTSD in women with trauma histories. Research on the role of estrogen in fear regulation may provide insight into novel treatment strategies for PTSD.