Estrogen levels are associated with extinction deficits in women with posttraumatic stress disorder

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 (E(2)) groups. Seventeen of 41 women (41.5%) in the low E(2) group and 15 of 40 women (37.5%) met criteria for PTSD in the high E(2) group.

Results: The results showed that all groups had equivalent levels of fear conditioning. However, we found significant interaction effects between high versus low E(2) 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 E(2) 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.

Conflict of interest statement

The authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Schematic illustration of the experimental paradigm. The previously reinforced conditioned stimulus (CS+) in the extinction session did not include the air blast (aversive stimulus [US]). CA−, nonreinforced conditioned stimulus; NA, noise probe alone.

Figure 2

Mean ± SE fear-potentiated startle during extinction across diagnostic and estrogen groups. *p < .05. E2, estradiol; PTSD, posttraumatic stress disorder.

Figure 3

Mean ± SE fear-potentiated startle across extinction phases comparing diagnostic groups within each estrogen group. Data shown are covaried for trauma exposure. All groups demonstrated a significant linear effect of Phase, p < .001. (A) Low estradiol (E2) groups. (B) High E2 groups. *p < .05; **p < .01. PTSD, posttraumatic stress disorder.