Palma-Gudiel Helena, Córdova-Palomera Aldo, Leza Juan Carlos, Fañanás Lourdes
Unity of Anthropology, Departament of Animal Biology, Faculty of Biology, Instituto de Biomedicina (IBUB), Universidad de Barcelona (UB), Av. Diagonal, 643, 08028 Barcelona, Spain.
Unity of Anthropology, Departament of Animal Biology, Faculty of Biology, Instituto de Biomedicina (IBUB), Universidad de Barcelona (UB), Av. Diagonal, 643, 08028 Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), C/ Doctor Esquerdo, 46, 28007 Madrid, Spain.
Neurosci Biobehav Rev. 2015 Aug;55:520-35. doi: 10.1016/j.neubiorev.2015.05.016. Epub 2015 Jun 11.
Early life stress (ELS) is a known risk factor for suffering psychopathology in adulthood. The hypothalamic-pituitary-adrenal (HPA) axis has been described to be deregulated in both individuals who experienced early psychosocial stress and in patients with a wide range of psychiatric disorders. The NR3C1 gene codes for the glucocorticoid receptor, a key element involved in several steps of HPA axis modulation. In this review, we gather existing evidence linking NR3C1 methylation pattern with either ELS or psychopathology. We summarize that several types of ELS have been frequently associated with NR3C1 hypermethylation whereas hypomethylation has been continuously found to be associated with post-traumatic stress disorder. In light of the reported findings, the main concerns of ongoing research in this field are the lack of methodological consensus and selection of CpG sites. Further studies should target individual CpG site methylation assessment focusing in biologically relevant areas such as transcription factor binding regions whereas widening the examined sequence in order to include all non-coding first exons of the NR3C1 gene in the analysis.
早年生活应激（ELS）是成年后患精神病理学的已知风险因素。下丘脑-垂体-肾上腺（HPA）轴在经历过早期心理社会应激的个体以及患有多种精神疾病的患者中均被描述为调节异常。NR3C1基因编码糖皮质激素受体，这是参与HPA轴调节多个步骤的关键要素。在本综述中，我们收集了将NR3C1甲基化模式与ELS或精神病理学联系起来的现有证据。我们总结发现，几种类型的ELS经常与NR3C1高甲基化相关，而低甲基化一直被发现与创伤后应激障碍相关。鉴于已报道的研究结果，该领域正在进行的研究的主要关注点是缺乏方法学共识以及CpG位点的选择。进一步的研究应针对个体CpG位点甲基化评估，重点关注生物学相关区域，如转录因子结合区域，同时拓宽检测序列，以便在分析中纳入NR3C1基因的所有非编码第一外显子。
