Epidemiologic and genetic studies suggest common environmental and genetic risk factors for a number of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Genetic and environmental factors, especially adverse life events, not only have main effects on disease development but also may interact to shape risk and resilience. Such gene by adversity interactions have been described for FKBP5, an endogenous regulator of the stress-neuroendocrine system, conferring risk for a number of psychiatric disorders. In this review, we present a molecular and cellular model of the consequences of FKBP5 by early adversity interactions. We illustrate how altered genetic and epigenetic regulation of FKBP5 may contribute to disease risk by covering evidence from clinical and preclinical studies of FKBP5 dysregulation, known cell-type and tissue-type expression patterns of FKBP5 in humans and animals, and the role of FKBP5 as a stress-responsive molecular hub modulating many cellular pathways. FKBP5 presents the possibility to better understand the molecular and cellular factors contributing to a disease-relevant gene by environment interaction, with implications for the development of biomarkers and interventions for psychiatric disorders.

中文翻译：

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通过精神疾病的环境相互作用了解支持基因的分子机制：FKBP5 模型

流行病学和遗传学研究表明，许多精神疾病存在常见的环境和遗传风险因素，包括抑郁症、双相情感障碍和精神分裂症。遗传和环境因素，尤其是不良生活事件，不仅对疾病的发展有主要影响，而且可能相互作用以形成风险和恢复力。这种通过逆境相互作用产生的基因已被描述为 FKBP5，一种压力-神经内分泌系统的内源性调节剂，赋予许多精神疾病的风险。在这篇综述中，我们通过早期逆境相互作用提出了 FKBP5 后果的分子和细胞模型。我们通过涵盖 FKBP5 失调的临床和临床前研究的证据来说明 FKBP5 的遗传和表观遗传调控的改变如何导致疾病风险，FKBP5 在人类和动物中的已知细胞类型和组织类型表达模式，以及 FKBP5 作为调节许多细胞通路的应激反应分子中枢的作用。FKBP5 提供了通过环境相互作用更好地了解导致疾病相关基因的分子和细胞因素的可能性，这对开发生物标志物和精神疾病干预措施具有重要意义。