母亲围产期压力和抑郁与婴儿出生后第一年 DNA 甲基化之间的关系。

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-22 DOI:10.1038/s41398-024-03148-8
Sarina Abrishamcar, Beryl C Zhuang, Mara Thomas, Nicole Gladish, Julia L MacIsaac, Meaghan J Jones, Elinor Simons, Theo J Moraes, Piush J Mandhane, Jeffrey R Brook, Padmaja Subbarao, Stuart E Turvey, Edith Chen, Gregory E Miller, Michael S Kobor, Anke Hüls
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引用次数: 0

摘要

怀孕期间和婴儿出生后第一年的产妇压力和抑郁影响着很大一部分母亲。孕产妇压力和抑郁与胎儿和儿童的不良结局以及儿童 DNA 甲基化(DNAm)差异有关。然而,孕产妇压力和抑郁与儿童不良健康结果之间的生物机制在很大程度上仍然未知。在此,我们旨在确定产前压力和抑郁是否与新生儿(n = 119)脐带血单核细胞 DNAm(CBMC-DNAm)的差异有关,以及产后压力和抑郁是否与加拿大健康婴儿纵向发展(CHILD)队列中 12 个月大儿童(n = 113)外周血单核细胞 DNAm(PBMC-DNAm)的差异有关。压力用 10 项感知压力量表 (PSS) 测量,抑郁用 20 项流行病学研究中心抑郁问卷 (CESD) 测量。压力和抑郁均在怀孕 18 周和 36 周以及产后 6 个月和 12 个月时进行纵向测量。我们使用稳健线性回归法进行了全表观基因组关联研究(EWAS),然后进行了敏感性分析,在分析中,我们使用培根法和凯特法对通货膨胀和未测量的混杂因素进行了偏差调整。为了量化母亲压力和抑郁的累积效应,我们创建了产前和产后逆境综合评分。我们发现,产前压力与 8 个 CpG 位点的 CBMC-DNAm 差异之间以及产前抑郁与 2 个 CpG 位点的 CBMC-DNAm 差异之间存在显着关联。此外,我们还发现,产后应激与 8 个 CpG 位点的 PBMC-DNAm 差异之间存在显著关联,产后抑郁与 11 个 CpG 位点的 PBMC-DNAm 差异之间存在显著关联。通过综合评分,我们进一步确定了 2 个与产前逆境显著相关的 CpG 位点和 7 个与产后逆境显著相关的 CpG 位点。包括 PLAGL1、HYMAI、BRD2 和 ERC2 在内的几个相关基因与胎儿不良结局和神经精神疾病有关。这些数据进一步支持了差异 DNAm 可能在孕产妇心理健康与儿童健康之间的关系中发挥作用这一发现。
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Association between maternal perinatal stress and depression and infant DNA methylation in the first year of life.

Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with differences in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with differences in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the 20-item Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured longitudinally at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To quantify the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. These data further support the finding that differential DNAm may play a role in the relationship between maternal mental health and child health.

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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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