Department of Pediatrics, Child & Family Research Institute, University of British Columbia, Vancouver, Canada.
PLoS One. 2010 Aug 16;5(8):e12201. doi: 10.1371/journal.pone.0012201.
Prenatal and early postnatal exposure to maternal depression may "program" childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.
METHODS/PRINCIPAL FINDINGS: Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2(nd) and 3(rd) trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2(nd) trimester depressed mood (p<0.05). Increased 2(nd) trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation.
These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.
产前和产后早期母亲抑郁暴露可能通过表观遗传过程（如 DNA 甲基化）“编程”儿童行为。亚甲基四氢叶酸还原酶（MTHFR）是用于 DNA 甲基化的甲基供体生成的重要酶。常见的 MTHFR C677T 变体与男性和非孕妇的抑郁有关，与 DNA 甲基化的整体变化有关。本研究调查了母亲 MTHFR C677T 基因型对产前母亲情绪的影响，以及它们对孕妇及其新生儿基因特异性甲基化的影响。由于其在行为中的潜在作用，评估了编码跨膜 5-羟色胺转运体的 SLC6A4 和编码脑源性神经营养因子的 BDNF 的基因特异性甲基化状态。
方法/主要发现：在妊娠第 2 和第 3 个三个月期间，通过爱丁堡产后抑郁量表（EPDS）和汉密尔顿抑郁量表（HAM-D）评估女性（n = 82，均服用叶酸）的抑郁情绪。在第 3 个三个月时，评估了 SLC6A4 和 BDNF 的甲基化状态母亲外周血白细胞和婴儿出生时脐带白细胞。MTHFR 677TT 基因型的女性在第 2 个三个月时有更大的抑郁情绪（p<0.05）。第 2 个三个月时增加的母亲抑郁情绪（EPDS 评分）与母亲和婴儿 SLC6A4 启动子甲基化减少有关（p<0.05），但对 BDNF 启动子甲基化没有影响。
这些发现表明，MTHFR C677T 变体与妊娠期间更大的抑郁情绪有关。我们进一步表明，产前暴露于母亲的抑郁情绪会影响基因特异性 DNA 甲基化模式。这些发现支持这样一种概念，即表观遗传过程的改变可能导致母亲抑郁对行为的发育编程。
