Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychology and Human Development, Peabody College of Vanderbilt University, Nashville, TN, USA.
Mol Psychiatry. 2022 Aug;27(8):3306-3315. doi: 10.1038/s41380-022-01592-w. Epub 2022 May 16.
The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers' attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood. We recruited 156 women oversampled for histories of depression, who completed psychiatric interviews and depression screening during pregnancy, then provided follow-up behavioral data on their children at 18 months. Buccal cell DNA was obtained from 32 of their infants for a large-scale analysis of methylation patterns across 5 × 10 individual CpG dinucleotides, using clustering-based significance criteria to control for multiple comparisons. We found that tens of thousands of individual infant CpGs were alternatively methylated in association with maternal attachment insecurity, maltreatment in childhood, and antenatal and postpartum depressive symptoms, including genes implicated in developmental patterning, cell-cell communication, hormonal regulation, immune function/inflammatory response, and neurotransmission. Density of DNA methylation at selected genes from the result set was also significantly associated with toddler socioemotional and behavioral problems. This is the first report to identify novel regions of the human infant genome at which DNA methylation patterns are associated longitudinally both with maternal characteristics and with offspring socioemotional and behavioral problems in toddlerhood.
早期环境，包括母体特征，为幼体提供了许多线索，从而影响其长期的身心健康。识别发生在可观察到的发育结果之前的最早的分子事件，可能有助于在身体和心理健康问题出现之前，识别出需要支持的儿童。在这项研究中，我们研究了母亲的依恋不安全感、虐待史和抑郁症状是否与婴儿的 DNA 甲基化模式改变有关，以及婴儿表观基因组中的这些相关性是否与幼儿期的社会情感和行为功能有关。我们招募了 156 名患有抑郁症病史的女性，她们在怀孕期间完成了精神病学访谈和抑郁筛查，然后在 18 个月时为孩子提供了后续的行为数据。我们从 32 名婴儿的口腔细胞中获取了 DNA，用于对 5×10 个个体 CpG 二核苷酸的甲基化模式进行大规模分析，使用基于聚类的显著标准来控制多重比较。我们发现，数万个婴儿 CpG 以与母亲依恋不安全感、儿童时期的虐待以及产前和产后抑郁症状相关的方式发生了替代性甲基化，包括与发育模式、细胞间通讯、激素调节、免疫功能/炎症反应和神经递质有关的基因。从结果集中选择的基因的 DNA 甲基化密度也与幼儿的社会情感和行为问题显著相关。这是第一项报告，表明人类婴儿基因组的新区域的 DNA 甲基化模式与母亲特征以及幼儿期后代的社会情感和行为问题呈纵向相关。
