Women and men differ in disease prevalence, symptoms, and progression rates for many psychiatric and neurological disorders. As more preclinical studies include both sexes in experimental design, an increasing number of sex differences in physiology and behavior have been reported. In the brain, sex‐typical behaviors are thought to result from sex‐specific patterns of neural activity in response to the same sensory stimulus or context. These differential firing patterns likely arise as a consequence of underlying anatomic or molecular sex differences. Accordingly, gene expression in the brains of females and males has been extensively investigated, with the goal of identifying biological pathways that specify or modulate sex differences in brain function. However, there is surprisingly little consensus on sex‐biased genes across studies and only a handful of robust candidates have been pursued in the follow‐up experiments. Furthermore, it is not known how or when sex‐biased gene expression originates, as few studies have been performed in the developing brain. Here we integrate molecular genetic and neural circuit perspectives to provide a conceptual framework of how sex differences in gene expression can arise in the brain. We detail mechanisms of gene regulation by steroid hormones, highlight landmark studies in rodents and humans, identify emerging themes, and offer recommendations for future research.

中文翻译：

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性别特征：脊椎动物大脑中基因表达的性别差异。

女性和男性在许多精神和神经疾病的患病率、症状和进展率方面存在差异。随着越来越多的临床前研究将男女纳入实验设计，越来越多的生理和行为方面的性别差异被报道。在大脑中，典型的性别行为被认为是由于对相同的感官刺激或环境做出反应的性别特异性神经活动模式造成的。这些不同的放电模式可能是由于潜在的解剖或分子性别差异而产生的。因此，人们对女性和男性大脑中的基因表达进行了广泛的研究，目的是确定指定或调节大脑功能性别差异的生物途径。然而，令人惊讶的是，跨研究对性别偏见基因几乎没有达成共识，并且在后续实验中只寻找了少数可靠的候选基因。此外，目前尚不清楚性别偏见基因表达是如何或何时起源的，因为在发育中的大脑中进行的研究很少。在这里，我们整合了分子遗传学和神经回路的观点，为大脑中基因表达的性别差异如何产生提供了一个概念框架。我们详细介绍了类固醇激素的基因调控机制，重点介绍了啮齿动物和人类的里程碑式研究，确定了新兴主题，并为未来的研究提供了建议。