Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle
Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle
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DOI：
10.1016/j.ynstr.2020.100213
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发表时间：
2020-05-01
影响因子：
5
通讯作者：
Epperson, C. Neill
中科院分区：
文献类型：
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作者：
Hantsoo, Liisa;Epperson, C. Neill
经前烦躁障碍 (PMDD) 是一种严重的情绪障碍，其核心症状是（情感不稳定、易怒、情绪低落、焦虑），并且对月经周期黄体期发生的压力敏感度增加。经前抑郁症 (PMDD) 可以被概念化为一种对神经活性类固醇激素 (NAS) 敏感性欠佳的疾病。在这篇综述中，我们描述了 NAS allopregnanolone (ALLO)，一种 GABA(A) 受体 (GABA(A)-R) 的正变构调节剂，在 PMDD 病理生理学中的作用。我们根据啮齿动物和人类研究的证据，回顾了 ALLO 和 GABA(A)-Rs 在情感症状表达方面相互作用受损的证据。我们讨论了由于 ALLO-GAB(A) 对 HPA 轴控制不良导致黄体期应激敏感性增加的证据。最后，我们描述了选择性血清素再摄取抑制剂 (SSRI) 和靶向 GABA(A)-R 的新药等治疗方法如何为经前抑郁症 (PMDD) 中 ALLO-GABA 功能受损提供证据。总之，文献支持这样的假设：经前抑郁症 (PMDD) 病理生理学根源于 GABA(A)-R 对整个月经周期动态 ALLO 波动的反应受损，表现为情感症状和生理应激反应调节不良。
Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with core symptoms (affective lability, irritability, depressed mood, anxiety) and increased sensitivity to stress occurring in the luteal phase of the menstrual cycle. PMDD can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones (NASs). In this review, we describe the role of the NAS allopregnanolone (ALLO), a positive allosteric modulator of the GABA(A) receptor (GABA(A)-R), in PMDD's pathophysiology. We review evidence of impaired interaction between ALLO and GABA(A)-Rs in terms of affective symptom expression, with evidence from rodent and human studies. We discuss evidence of increased luteal phase stress sensitivity as a result of poor ALLO-GAB(A) control of the HPA axis. Finally, we describe how treatments such as selective serotonin reuptake inhibitors (SSRIs) and new drugs targeting GABA(A)-Rs provide evidence for impaired ALLO-GABA function in PMDD. In sum, the literature supports the hypothesis that PMDD pathophysiology is rooted in impaired GABA(A)-R response to dynamic ALLO fluctuations across the menstrual cycle, manifesting in affective symptoms and poor regulation of physiologic stress response.