Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
BIH Biomedical Innovation Academy, Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, Berlin, Germany.
Transl Psychiatry. 2024 Oct 24;14(1):449. doi: 10.1038/s41398-024-03079-4.
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.
改变的恐惧条件反射和消退学习被认为是焦虑障碍的重要病因特征。女性患焦虑障碍的风险增加，并且已经证明恐惧条件反射受到月经周期阶段和循环性腺激素的影响。我们的研究目的是调查单独和联合使用雌二醇和孕酮对健康女性恐惧消退的影响。我们在健康女性中进行了一项安慰剂对照、随机研究，这些女性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。皮肤电导反应（SCR）作为主要的观察变量。在第 2 天测试前 2 小时，参与者服用含有安慰剂、雌二醇（2 毫克）、孕酮（400 毫克）或两者组合的药丸。我们检查了 116 名女性（平均年龄 25.7±6.0 岁），她们在恐惧获得训练中对 CS+的条件性 SCR 明显强于 CS-，表明成功地进行了恐惧学习。在恐惧消退训练开始时，雌二醇的给药降低了条件刺激之间的分化。在恐惧恢复测试中，雌二醇组对先前已消退的刺激表现出更高的 SCR 反应，即消退记忆受损。孕酮的给药对 SCR 没有任何显著影响。对恐惧增强的惊跳反应也没有影响。在我们的解释中，外源性雌二醇的给药影响了条件恐惧反应的消退，从而导致更强的恐惧恢复。从临床的角度来看，我们的发现表明雌二醇水平可能对暴露疗法的成功有影响，在计划暴露治疗时可以考虑这一点。
