van der Knaap L J, Riese H, Hudziak J J, Verbiest M M P J, Verhulst F C, Oldehinkel A J, van Oort F V A
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
1] Interdisciplinary Center Psychopathology and Emotion regulation, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands [2] Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Transl Psychiatry. 2014 Apr 8;4(4):e381. doi: 10.1038/tp.2014.22.
Stress early in life is a known risk factor for the development of affective disorders later in life. Epigenetic mechanisms, such as DNA methylation, may have an important role in mediating that risk. Recent epigenetic research reported on the long-term relationship between traumatic stress in childhood and DNA methylation in adulthood. In this study, we examined the impact of various types of stress (perinatal stress, stressful life events (SLEs) and traumatic youth experiences) on methylation of the glucocorticoid receptor gene (NR3C1) in the blood of a population sample of 468 adolescents (50.4% female, mean age 16.1 years). Second, we determined whether stress at different ages was associated with higher NR3C1 methylation. NR3C1 methylation rates were higher after exposure to SLEs and after exposure to traumatic youth experiences. NR3C1 methylation in adolescence was not higher after exposure to perinatal stress. Experience of SLEs in adolescence was associated with a higher NR3C1 methylation, independently of childhood SLEs. We demonstrate that not only traumatic youth experiences but also (more common) SLEs are associated with higher NR3C1 methylation. In addition, our findings underline the relevance of adolescent stress for epigenetic changes in the NR3C1 gene.
早年的压力是已知的日后患情感障碍的风险因素。表观遗传机制，如DNA甲基化，可能在介导这种风险中起重要作用。最近的表观遗传学研究报道了童年创伤性压力与成年期DNA甲基化之间的长期关系。在本研究中，我们调查了468名青少年（50.4%为女性，平均年龄16.1岁）的人群样本血液中，各种类型的压力（围产期压力、应激性生活事件（SLE）和创伤性青少年经历）对糖皮质激素受体基因（NR3C1）甲基化的影响。其次，我们确定了不同年龄的压力是否与更高的NR3C1甲基化有关。暴露于SLE和创伤性青少年经历后，NR3C1甲基化率更高。暴露于围产期压力后，青少年期的NR3C1甲基化并不更高。青少年期的SLE经历与更高的NR3C1甲基化有关，与童年期的SLE无关。我们证明，不仅创伤性青少年经历，而且（更常见的）SLE都与更高的NR3C1甲基化有关。此外，我们的研究结果强调了青少年压力与NR3C1基因表观遗传变化的相关性。
