4.0 Article

Impact of hormonal contraceptives on sex differences in fear conditioning and fear extinction in PTSD

Journal

LEARNING & MEMORY
Volume 29, Issue 9, Pages 332-339

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/lm.053597.122

Keywords

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Funding

  1. Department of Veteran Affairs Clinical Science Research and Development [1I01CX000720-01A2]
  2. Department of Defense [PR192475]
  3. Heart and Armor Foundation
  4. Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration, Veterans Administration Medical Center, San Francisco, California
  5. National Center for Research Resources
  6. National Center for Advancing Translational Sciences
  7. Office of the Director, National Institutes of Health through University of California at San Francisco-Clinical and Translational Science Institute [KL2 RR024130]
  8. University of California at San Francisco-Clinical and Translational Science Institute

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Sex differences in fear conditioning and extinction, as well as the effects of hormones, may contribute to the development of PTSD. Hormonal contraceptives may enhance fear conditioning and extinction. Understanding the impact of sex and hormones on fear processes can provide insights into the pathophysiology of PTSD and potentially lead to sex-specific advancements in treatment.
Sex differences in the neurobiological mechanisms involved in fear conditioning and extinction have been suggested to contribute to differential vulnerability for the development of posttraumatic stress disorder (PTSD) in women compared with men. Reproductive hormones, such as estradiol, have been shown to facilitate fear conditioning and extinction learning and may explain some of these differences. However, the effect of commonly used hormonal contraceptives on the neurobiological mechanisms of fear conditioning and extinction is poorly understood. A laboratory study was conducted in trauma-exposed men and women with and without full or partial PTSD to examine effects of sex and use of hormonal birth control on fear conditioning, fear extinction learning, and extinction retention. Participants underwent fear conditioning with stimuli that were paired (CS+) or unpaired (CS-) with shock. Extinction learning occurred 72 h later, and extinction retention was tested 1 wk after extinction. Women on hormonal contraceptives (HCs) demonstrated enhanced acquisition of fear conditioning and enhanced extinction of fear as compared with women off hormonal birth control and men. While clinical implications have yet to be determined, these results suggest that hormonal contraceptives may facilitate learning during both fear acquisition and extinction. Understanding the impact of sex and hormones on fear conditioning and extinction processes may lead to new insights into the pathophysiology of PTSD and result in advancements in treatment that may vary by sex.

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