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-GABA 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.

经前烦躁症 (PMDD) 是一种严重的情绪障碍，具有核心症状（情绪不稳、易怒、情绪低落、焦虑）和对月经周期黄体期发生的压力的敏感性增加。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 的病理生理学中的作用。我们审查了 ALLO 和 GABA _A之间相互作用受损的证据-Rs 在情感症状表达方面，来自啮齿动物和人类研究的证据。我们讨论了由于对 HPA 轴的 ALLO-GABA 控制不佳导致黄体期应力敏感性增加的证据。最后，我们描述了选择性 5-羟色胺再摄取抑制剂 (SSRIs) 和靶向 GABA _A- Rs 的新药等治疗方法如何为PMDD 中 ALLO-GABA 功能受损提供证据。总之，文献支持以下假设：PMDD 病理生理学源于 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。