Postpartum depression (PPD) is a common major depressive episode surrounding childbirth, with estimated rates ranging from 5.5% to 23.5% of all live births across Europe and the USA based on the presence of key symptoms. PPD has been associated with significant impairments in both maternal functioning and mother-infant attachment, and these impairments can have lasting effects on the emotional and cognitive development of children. Although the precise pathophysiology of PPD is unknown, preclinical findings suggest that large fluctuations in neurosteroid hormone levels can induce physiological plasticity in the expression of functional GABA_A receptors during pregnancy and the postpartum period, and that deficits in this plasticity may underpin a biological mechanism that contributes to the manifestation of depressive symptoms. Here, we review the controlled clinical trials to date that have assessed the efficacy of pharmacological treatments for PPD, including oestradiol, selective serotonin reuptake inhibitors, brexanolone (an iv formulation of allopregnanolone) and an investigational neuroactive steroid and GABA_A positive allosteric modulator, zuranolone. Coupled with the GABAergic deficits implicated in major depressive disorder, these findings highlight not only the potential role of GABA_A receptor plasticity in the pathophysiology of PPD, but also the novel therapeutic approach of using positive allosteric modulators targeting GABAergic transmission to treat women affected by PPD.

中文翻译：

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开发用于治疗产后抑郁症的神经活性类固醇

产后抑郁症 (PPD) 是一种常见的与分娩有关的重度抑郁症，根据关键症状的存在，估计在欧洲和美国所有活产中的发生率从 5.5% 到 23.5% 不等。PPD 与母亲功能和母婴依恋的严重损害有关，这些损害会对儿童的情绪和认知发展产生持久影响。虽然 PPD 的确切病理生理学尚不清楚，但临床前研究结果表明，神经类固醇激素水平的大幅波动可诱导功能性 GABA _{A表达的生理可塑性。}怀孕和产后期间的受体，并且这种可塑性的缺陷可能是导致抑郁症状表现的生物学机制的基础。在这里，我们回顾了迄今为止评估 PPD 药物治疗效果的对照临床试验，包括雌二醇、选择性 5-羟色胺再摄取抑制剂、brexanolone（一种异孕酮的静脉内制剂）和研究中的神经活性类固醇和 GABA _A正变构调节剂 zuranolone . 再加上与重度抑郁症有关的 GABA 能缺陷，这些发现不仅突出了 GABA _{A的潜在作用}PPD 病理生理学中的受体可塑性，也是使用靶向 GABA 能传递的正变构调节剂治疗受 PPD 影响的女性的新治疗方法。