Prior studies identified DNA methylation (DNA_M) changes in a regulatory region within the FK506 binding protein 5 (FKBP5) gene as a crucial mediator of long-term negative health outcomes following early adversity. A critical mechanism underlying this link, in turn, has been suggested to be epigenetically induced dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. The purpose of this study was thus to investigate associations of FKBP5 DNA_M with both acute and chronic cortisol output. Two hundred adults with differential exposure to childhood trauma (CT) were underwent a laboratory stressor (Trier Social Stress Test) and provided salivary samples for the analysis of acute cortisol stress responses. In addition, hair cortisol concentrations were determined as a valid measure of integrated long-term cortisol levels. Whole blood samples were drawn for DNA_M analyses of FKBP5 intron 7 via bisulfite pyrosequencing. In contrast to most prior work, only healthy participants were included in order to disentangle the effects of trauma exposure per se from those related to mental disorders. First, our findings did not reveal strong evidence for a robust effect of CT on FKBP5 intron 7 DNA_M status, even if genetic predisposition (rs1360780 genotype) was taken into account. Second, FKBP5 DNA_M levels were found to be unrelated to acute cortisol stress reactivity and long-term cortisol concentration in hair. The failure to demonstrate a significant association between CT and FKBP5 DNA_M in an exclusively healthy sample could be interpreted as suggesting that individuals’ mental health status may be a critical modulator of previously observed effects.

先前的研究确定了FK506 结合蛋白 5 ( FKBP5 ) 基因内调节区域的DNA 甲基化 (DNA _M ) 变化是早期逆境后长期负面健康结果的关键介质。反过来，这种联系背后的一个关键机制被认为是表观遗传诱导的下丘脑-垂体-肾上腺 (HPA) 轴的失调。因此，本研究的目的是调查FKBP5 DNA _{M的关联。}具有急性和慢性皮质醇输出。200 名儿童期创伤 (CT) 暴露不同的成年人接受了实验室压力源（特里尔社会压力测试），并提供了唾液样本用于分析急性皮质醇应激反应。此外，头发皮质醇浓度被确定为综合长期皮质醇水平的有效衡量标准。通过亚硫酸氢盐焦磷酸测序提取全血样本用于FKBP5内含子 7的 DNA _M分析。与大多数先前的工作相比，只包括健康的参与者，以便将创伤暴露本身的影响与与精神障碍相关的影响区分开来。首先，我们的研究结果并未揭示 CT 对FKBP5内含子 7 DNA _{M的强烈影响的有力证据。}即使考虑到遗传易感性（rs1360780基因型）也是如此。其次，发现FKBP5 DNA _M水平与急性皮质醇应激反应和头发中的长期皮质醇浓度无关。在完全健康的样本中未能证明 CT 和FKBP5 DNA _M之间存在显着关联可以解释为表明个人的心理健康状况可能是先前观察到的影响的关键调节剂。