Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging,Biological Psychiatry

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Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging
Biological Psychiatry ( IF 10.6 ) Pub Date : 2021-08-19 , DOI: 10.1016/j.biopsych.2021.07.025
Megan G McGill ₁ , Irina Pokhvisneva ₁ , Andrew S Clappison ₁ , Lisa M McEwen ₂ , Roseriet Beijers ₃ , Marieke S Tollenaar ₄ , Hung Pham ₅ , Michelle Z L Kee ₆ , Elika Garg ₁ , Euclides J de Mendonça Filho ₇ , Neerja Karnani ₈ , Patricia P Silveira ₁ , Michael S Kobor ₉ , Carolina de Weerth ₁₀ , Michael J Meaney ₁₁ , Kieran J O'Donnell ₁₂

Affiliation

Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, and Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, Quebec, Canada.
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Developmental Psychology, Radboud University, Nijmegen, the Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, the Netherlands.
Department of Clinical Psychology, Institute of Psychology and Leiden Institute for Brain and Cognition, Leiden University, Leiden, the Netherlands.
Yale Child Study Center and Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut.
Singapore Institute for Clinical Sciences, Singapore.
Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Bioinformatics Institute, Agency for Science, Technology, and Research, Singapore.
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada; Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada.
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, the Netherlands.
Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, and Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, Quebec, Canada; Singapore Institute for Clinical Sciences, Singapore; Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada; Department of Psychiatry, and Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, Quebec, Canada; Yale Child Study Center and Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, Connecticut; Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada.

Background

The fetal origins of mental health is a well-established framework that currently lacks a robust index of the biological embedding of prenatal adversity. The Pediatric-Buccal-Epigenetic (PedBE) clock is a novel epigenetic tool that associates with aspects of the prenatal environment, but additional validation in longitudinal datasets is required. Likewise, the relationship between prenatal maternal mental health and the PedBE clock has not been described.

Methods

Longitudinal cohorts from the Netherlands (Basal Influences on Baby Development [BIBO] n = 165) and Singapore (Growing Up in Singapore Towards Healthy Outcomes [GUSTO] n = 340) provided data on prenatal maternal anxiety and longitudinal assessments of buccal cell–derived genome-wide DNA methylation assessed at 6 and 10 years of age in BIBO, and at 3, 9, and 48 months of age in GUSTO. Measures of epigenetic age acceleration were calculated using the PedBE clock and benchmarked against an established multi-tissue epigenetic predictor.

Results

Prenatal maternal anxiety predicted child PedBE epigenetic age acceleration in both cohorts, with effects largely restricted to males and not females. These results were independent of obstetric, socioeconomic, and genetic risk factors, with a larger effect size for prenatal anxiety than depression. PedBE age acceleration predicted increased externalizing symptoms in males from mid- to late childhood in the BIBO cohort only.

Conclusions

These findings point to the fetal origins of epigenetic age acceleration and reveal an increased sensitivity in males. Convergent evidence underscores the societal importance of providing timely and effective mental health support to pregnant individuals, which may have lasting consequences for both mother and child.

中文翻译：

母亲产前焦虑和表观遗传衰老的胎儿起源

背景

心理健康的胎儿起源是一个成熟的框架，目前缺乏一个强有力的指标来衡量产前逆境的生物学嵌入。儿科-口腔-表观遗传 (PedBE) 时钟是一种新的表观遗传工具，与产前环境的各个方面相关联，但需要在纵向数据集中进行额外验证。同样，尚未描述产前产妇心理健康与 PedBE 时钟之间的关系。

方法

来自荷兰（Basal Influences on Baby Development [BIBO] n = 165）和新加坡（Growing Up in Singapore Towards Healthy Outcomes [GUSTO] n = 340）的纵向队列提供了产前母亲焦虑和口腔细胞衍生基因组纵向评估的数据BIBO 在 6 岁和 10 岁时以及在 GUSTO 中在 3、9 和 48 个月时评估了全范围的 DNA 甲基化。使用 PedBE 时钟计算表观遗传年龄加速的测量值，并以已建立的多组织表观遗传预测因子为基准。