More than two-thirds of patients suffering from stress-related disorders are women but over two-thirds of suicide completers are men. These are just some examples of the many sex differences in the prevalence and manifestations of stress-related disorders, such as major depressive disorder, post-traumatic stress disorder, and anxiety disorders, which have been extensively documented in clinical research. Nonetheless, the molecular origins of this sex dimorphism are still quite obscure. In response to this lack of knowledge, the NIH recently advocated implementing sex as biological variable in the design of preclinical studies across disciplines. As a result, a newly emerging field within psychiatry is trying to elucidate the molecular causes underlying the clinically described sex dimorphism. Several studies in rodents and humans have already identified many stress-related genes that are regulated by acute and chronic stress in a sex-specific fashion. Furthermore, current transcriptomic studies have shown that pathways and networks in male and female individuals are not equally affected by stress exposure. In this review, we give an overview of transcriptional studies designed to understand how sex influences stress-specific transcriptomic changes in rodent models, as well as human psychiatric patients, highlighting the use of different methodological techniques. Understanding which mechanisms are more affected in males, and which in females, may lead to the identification of sex-specific mechanisms, their selective contribution to stress susceptibility, and their role in the development of stress-related psychiatric disorders.

中文翻译：

---

性别差异：男性和女性大脑中压力暴露的转录特征。

患有与压力有关的疾病的患者中，三分之二以上是女性，而自杀完成者中有三分之二以上是男性。这些只是应激相关疾病患病率和表现中许多性别差异的一些例子，例如重大抑郁症，创伤后应激障碍和焦虑症，这些已在临床研究中广泛记录。但是，这种性别二态性的分子起源仍然很模糊。由于缺乏知识，美国国立卫生研究院最近提倡在跨学科的临床前研究设计中将性别作为生物变量。结果，精神病学领域的一个新兴领域正在试图阐明临床描述的性别二态性背后的分子原因。在啮齿动物和人类中进行的一些研究已经确定了许多与压力有关的基因，这些基因受性别特定的急性和慢性压力调节。此外，当前的转录组学研究表明，男性和女性个体的途径和网络不受压力暴露的同等影响。在这篇综述中，我们提供了转录研究的概述，旨在了解性别如何影响啮齿动物模型以及人类精神病患者的应激特异性转录组变化，重点介绍了不同方法学方法的使用。了解哪些机制在男性中受影响最大，在女性中哪些机制可能导致识别性别特异性机制，其对压力易感性的选择性贡献以及它们在与压力有关的精神疾病中的作用。