Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Biol Psychiatry. 2018 May 15;83(10):821-830. doi: 10.1016/j.biopsych.2018.01.021. Epub 2018 Mar 21.
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.
流行病学和遗传学研究表明，许多精神疾病，包括抑郁症、双相情感障碍和精神分裂症，都存在共同的环境和遗传风险因素。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，影响风险和适应能力。FKBP5 是应激-神经内分泌系统的内源性调节剂，其基因与逆境的相互作用已被描述为多种精神疾病的风险因素。在这篇综述中，我们提出了一个 FKBP5 早期逆境相互作用的分子和细胞模型。我们通过覆盖 FKBP5 失调的临床和临床前研究、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 作为应激反应分子枢纽调节许多细胞途径的作用的证据，说明了 FKBP5 基因的遗传和表观遗传调节的改变如何导致疾病风险。FKBP5 为更好地理解导致疾病相关基因与环境相互作用的分子和细胞因素提供了可能性，这对精神疾病的生物标志物和干预措施的发展具有重要意义。
