Mendonça Mariana S, Mangiavacchi Paula M, Mendes Ana V, Loureiro Sonia R, Martín-Santos Rocio, Glória Leonardo S, Marques Wilson, De Marco Silmara P G, Kanashiro Milton M, Hallak Jaime E C, Crippa José A S, Rios Álvaro F L
Laboratory of Biotechnology, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil.
Laboratory of Reproduction and Animal Breeding, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro 28013-602, Brazil.
J Affect Disord. 2023 Jun 15;331:287-299. doi: 10.1016/j.jad.2023.03.031. Epub 2023 Mar 16.
The FKBP5 and NR3C1 genes play an important role in stress response, thus impacting mental health. Stress factor exposure in early life, such as maternal depression, may contribute to epigenetic modifications in stress response genes, increasing the susceptibility to different psychopathologies. The present study aimed to evaluate the DNA methylation profile in maternal-infant depression in regulatory regions of the FKBP5 gene and the alternative promoter of the NR3C1 gene.
We evaluated 60 mother-infant pairs. The levels of DNA methylation were analyzed by the MSRED-qPCR technique.
We observed an increased DNA methylation profile in the NR3C1 gene promoter in children with depression and children exposed to maternal depression (p < 0.05). In addition, we observed a correlation of DNA methylation between mothers and offspring exposed to maternal depression. This correlation shows a possible intergenerational effect of maternal MDD exposure on the offspring. For FKBP5, we found a decrease in DNA methylation at intron 7 in children exposed to maternal MDD during pregnancy and a correlation of DNA methylation between mothers and children exposed to maternal MDD (p < 0.05).
Although the individuals of this study are a rare group, the sample size of the study was small, and we evaluated the DNA methylation of only one CpG site for each region.
These results indicate changes in DNA methylation levels in regulatory regions of FKBP5 and NR3C1 in the mother-child MDD context and represent a potential target of studies to understand the depression etiology and how it occurs between generations.
FKBP5和NR3C1基因在应激反应中起重要作用，从而影响心理健康。早年生活中的应激因素暴露，如母亲抑郁，可能导致应激反应基因的表观遗传修饰，增加患不同精神疾病的易感性。本研究旨在评估FKBP5基因调控区和NR3C1基因替代启动子在母婴抑郁中的DNA甲基化谱。
我们评估了60对母婴。通过MSRED-qPCR技术分析DNA甲基化水平。
我们观察到抑郁儿童和暴露于母亲抑郁的儿童中，NR3C1基因启动子的DNA甲基化谱增加（p < 0.05）。此外，我们观察到暴露于母亲抑郁的母亲和后代之间的DNA甲基化存在相关性。这种相关性表明母亲患重度抑郁症对后代可能存在代际效应。对于FKBP5，我们发现孕期暴露于母亲重度抑郁症的儿童中，内含子7的DNA甲基化减少，且暴露于母亲重度抑郁症的母亲和儿童之间存在DNA甲基化相关性（p < 0.05）。
尽管本研究的个体是一个罕见群体，但研究样本量较小，且我们仅评估了每个区域的一个CpG位点的DNA甲基化。
这些结果表明在母婴重度抑郁症背景下，FKBP5和NR3C1调控区的DNA甲基化水平发生了变化，这代表了理解抑郁症病因及其代际发生机制的研究的潜在靶点。
