Inhibition of fear is differentially associated with cycling estrogen levels in women

Ebony M. Glover · Kristina B. Mercer · Seth Davin Norrholm · Erica Duncan · Bekh Bradley · Kerry James Ressler +1 more

93 citations0/0 files storedJournal of Psychiatry and Neuroscience

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Posttraumatic Stress Disorder Research Memory and Neural Mechanisms Stress Responses and Cortisol

Abstract

BACKGROUND: Although the prevalence of posttraumatic stress disorder (PTSD) is twice as high in women as it is in men, the role of estrogen in the risk for PTSD is not well understood. Deficits in fear inhibition and impaired safety signal learning may be biomarkers for PTSD. We examined menstrual cycle phase and serum estradiol levels in naturally cycling women while they were undergoing a novel conditioned inhibition procedure that measured their ability to discriminate between cues representing danger versus safety and to inhibit fear in the presence of safety cues. METHODS: Sample 1 included healthy participants in whom we compared inhibition of fearpotentiated startle during the follicular (lower estrogen) and luteal (higher estrogen) phases of the menstrual cycle. We used the same paradigm in a traumatized clinical population (sample 2) in whom we compared low versus high estradiol levels. RESULTS: In both samples, we found that lower estrogen in cycling women was associated with impaired fear inhibition. LIMITATIONS: In the clinical sample, the low estradiol group was on average older than the high estradiol group owing to the random recruitment approach; we did not exclude participants based on hormonal status or menopause. CONCLUSION: Our results suggest that the lower estrogen state during normal menstrual cycling may contribute to risk for anxiety disorders through dysregulated fear responses.

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References

1995Posttraumatic Stress Disorder in the National Comorbidity Survey 2006Sex differences in trauma and posttraumatic stress disorder: A quantitative review of 25 years of research.2007Gender differences in posttraumatic stress disorder.2008Influence of Child Abuse on Adult Depression 2000Comparison of the PTSD symptom scale–interview version and the clinician‐administered PTSD scale 2009Trauma exposure and stress-related disorders in inner city primary care patients 2011Impaired safety signal learning may be a biomarker of PTSD 2010Impaired fear inhibition is a biomarker of PTSD but not depression

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2018The clinical applications and practical relevance of human conditioning paradigms for posttraumatic stress disorder 2018Estrogen, progesterone, and the menstrual cycle: A systematic review of fear learning, intrusive memories, and PTSD 2016Functional evaluation of a PTSD-associated genetic variant: estradiol regulation and ADCYAP1R1 2016Developmental Contributors to Trauma Response: The Importance of Sensitive Periods, Early Environment, and Sex Differences

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