Observations of the disproportionate incidence of depression in women compared with men have long preceded the recent explosion of interest in sex differences. Nonetheless, the source and implications of this epidemiologic sex difference remain unclear, as does the practical significance of the multitude of sex differences that have been reported in brain structure and function. In this article, we attempt to provide a framework for thinking about how sex and reproductive hormones (particularly estradiol as an example) might contribute to affective illness. After briefly reviewing some observed sex differences in depression, we discuss how sex might alter brain function through hormonal effects (both organizational (programmed) and activational (acute)), sex chromosome effects, and the interaction of sex with the environment. We next review sex differences in the brain at the structural, cellular, and network levels. We then focus on how sex and reproductive hormones regulate systems implicated in the pathophysiology of depression, including neuroplasticity, genetic and neural networks, the stress axis, and immune function. Finally, we suggest several models that might explain a sex-dependent differential regulation of affect and susceptibility to affective illness. As a disclaimer, the studies cited in this review are not intended to be comprehensive but rather serve as examples of the multitude of levels at which sex and reproductive hormones regulate brain structure and function. As such and despite our current ignorance regarding both the ontogeny of affective illness and the impact of sex on that ontogeny, sex differences may provide a lens through which we may better view the mechanisms underlying affective regulation and dysfunction.

中文翻译：

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性别差异和情感障碍的神经生物学。

与男性相比，女性抑郁症发病率不成比例的观察早在最近对性别差异的兴趣爆发之前就已经出现了。尽管如此，这种流行病学性别差异的来源和影响仍不清楚，大脑结构和功能中已报道的大量性别差异的实际意义也不清楚。在本文中，我们试图提供一个框架来思考性激素和生殖激素（尤其是雌二醇作为例子）如何导致情感疾病。在简要回顾了一些观察到的抑郁症性别差异之后，我们讨论了性如何通过荷尔蒙效应（包括组织性（程序性）和激活性（急性））、性染色体效应以及性与环境的相互作用来改变大脑功能。我们接下来在结构、细胞和网络水平上回顾大脑中的性别差异。然后，我们关注性激素和生殖激素如何调节与抑郁症的病理生理学有关的系统，包括神经可塑性、遗传和神经网络、压力轴和免疫功能。最后，我们提出了几个模型，这些模型可以解释情感和情感疾病易感性的性别依赖性差异调节。作为免责声明，本综述中引用的研究并非旨在全面，而是作为性激素和生殖激素调节大脑结构和功能的众多水平的示例。因此，尽管我们目前对情感疾病的个体发育和性对个体发育的影响一无所知，