Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.

中文翻译：

---

重度抑郁症 (MDD) 的性别差异和用于抑郁症研究的临床前动物模型


抑郁症和相关的情绪障碍对健康、生活质量和全球经济构成了巨大的负担，女性一生中患抑郁症的风险大约是男性的两倍。在这里，我们回顾了人类大脑生理学中的性别差异，这些差异可能与女性对重度抑郁症（MDD）的易感性增加有关。此外，我们总结了数十年使用动物模型研究情绪功能障碍的临床前研究，揭示了可能构成性别差异和疾病病因学的一些潜在分子、细胞和回路水平机制。我们特别强调最近的一系列研究，这些研究证明了从腹侧海马到伏核的回路的核心贡献，以及该回路兴奋性的固有性别差异如何预测和驱动抑郁相关行为。本综述涵盖的研究结果强调，仍然需要使用临床前模型和特定回路策略进行研究，以揭示可能导致 MDD 和其他情绪障碍的潜在性别特异性诊断、预后、预防和/或治疗的分子和生理机制。 。