Effects of separate and combined estradiol and progesterone administration on fear extinction in healthy pre-menopausal women.

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-24 DOI:10.1038/s41398-024-03079-4
Michael Kaczmarczyk, Christian Eric Deuter, Hanna Deus, Anna Kallidou, Christian J Merz, Julian Hellmann-Regen, Christian Otte, Katja Wingenfeld
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Abstract

Altered fear conditioning and extinction learning are discussed as key etiological features in anxiety disorders. Women have an increased risk for anxiety disorders and fear conditioning has been shown to be influenced by the menstrual cycle phase and circulating gonadal hormones. The objective of our study was to investigate the effects of separate and combined estradiol and progesterone administration on fear extinction in healthy women. We conducted a placebo-controlled, randomized study in healthy women, who completed a fear conditioning paradigm on three consecutive days: fear acquisition training on day 1, fear extinction training on day 2, and return of fear test on day 3. Skin conductance responses (SCRs) served as main outcome variable. Two hours before testing on day 2, participants received pills containing either placebo, estradiol (2 mg), progesterone (400 mg) or the combination of both. We examined 116 women (mean age 25.7 ± 6.0 years), who showed significantly stronger conditioned SCRs to the CS+ than CS- during fear acquisition training indicating successful fear learning. At the beginning of the fear extinction training, estradiol administration reduced the differentiation between the conditioned stimuli. In the return of fear test, the estradiol groups showed heightened SCR responses to the previously extinguished stimulus, i.e., impaired extinction recall. Administration of progesterone did not have any significant influence on SCRs. There were also no effects on fear potentiated startle response. In our interpretation, exogenous estradiol administration affected the extinction of the conditioned fear response which led subsequently to a stronger return of fear. From a clinical perspective our findings suggest that estradiol levels may have an influence on the success of exposure therapy and could be taken into consideration when planning exposure sessions.

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单独和联合服用雌二醇和黄体酮对绝经前健康妇女恐惧消退的影响。
恐惧条件反射和消退学习的改变是焦虑症的主要病因。女性罹患焦虑症的风险更高,而恐惧条件反射已被证明会受到月经周期阶段和循环中的性腺激素的影响。我们的研究旨在调查单独或联合服用雌二醇和孕酮对健康女性恐惧消退的影响。我们对健康女性进行了一项安慰剂对照随机研究,她们在连续三天内完成了恐惧条件反射范式:第1天进行恐惧获得训练,第2天进行恐惧消退训练,第3天进行恐惧恢复测试。皮肤传导反应(SCR)是主要的结果变量。在第 2 天测试前两小时,参与者服用含有安慰剂、雌二醇(2 毫克)、黄体酮(400 毫克)或两者结合的药片。我们对 116 名女性(平均年龄为 25.7 ± 6.0 岁)进行了研究,在恐惧获得训练期间,她们对 CS+ 的条件 SCR 明显强于 CS-,这表明恐惧学习取得了成功。在恐惧消退训练开始时,雌二醇会降低条件刺激之间的差异。在恐惧回归测试中,雌二醇组对先前熄灭的刺激表现出更高的SCR反应,即熄灭回忆受损。黄体酮对SCR没有显著影响。对恐惧强直性惊吓反应也没有影响。根据我们的解释,外源性雌二醇会影响条件性恐惧反应的消退,从而导致更强的恐惧恢复。从临床角度来看,我们的研究结果表明,雌二醇水平可能会影响暴露疗法的成功与否,因此在计划暴露疗程时应加以考虑。
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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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