Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Sammallahti, Sara; ..., Cecil, Charlotte; Tiemeier, Henning; Lahri, Jari,  "Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation." Molecular Psychiatry: 1-14

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. ...

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Childhood maltreatment and DNA methylation: A systematic review

Cecil, Charlotte AM, Yuning Zhang, and Tobias Nolte. "Childhood maltreatment and DNA methylation: A systematic review." Neuroscience & Biobehavioral Reviews (2020).

  • We review human studies on childhood maltreatment and DNA methylation. 
  • The 72 studies identified were mainly retrospective and candidate-gene focussed. 
  • While studies generally support a relationship, evidence to date is inconsistent. 
  • Limitations include a lack of longitudinal data, low replication and confounding. 
  • We provide 12 concrete recommendations for moving the field forward.

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The impact of early life stress in later life

Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity

Learn more about the project and its objectives on Cordis - EU research results.

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Identifying Causative Mechanisms Linking Early-Life Stress to Psycho-Cardio-Metabolic Multi-Morbidity: The EarlyCause Project

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Introduction: Depression, cardiovascular diseases and diabetes are among the major non-communicable diseases, leading to significant disability and mortality worldwide. These diseases may share environmental and genetic determinants associated with multimorbid patterns. Stressful early-life events are among the primary factors associated with the development of mental and physical diseases. However, possible causative mechanisms linking early life stress (ELS) with psycho-cardio-metabolic (PCM) multi-morbidity are not well understood. This prevents a full understanding of causal pathways towards shared risk of these diseases and the development of coordinated preventive and therapeutic interventions.
Methods and analysis: This paper describes the study protocol for EarlyCause, a large-scale and inter-disciplinary research project funded by the European Union’s Horizon 2020 research and innovation programme. The project takes advantage of human longitudinal birth cohort data, animal studies and cellular models to test the hypothesis of shared mechanisms and molecular pathways by which ELS shape an individual’s physical and mental health in adulthood. The study will research in detail how ELS converts into biological signals embedded simultaneously or sequentially in the brain, the cardiovascular and metabolic systems. The research will mainly focus on four biological processes including possible alterations of the epigenome, neuroendocrine system, inflammatome, and the gut microbiome. Life course models will integrate the role of modifying factors as sex, socioeconomics, and lifestyle with the goal to better identify groups at risk as well as inform promising strategies to reverse the possible mechanisms and/or reduce the impact of ELS on multi-morbidity development in high-risk individuals. These strategies will help better manage the impact of multi-morbidity on human health and the associated risk.
Ethics and dissemination: The study has been approved by the Ethics Board of the European Commission. The results will be published in peer-reviewed academic journals, and disseminated to and communicated with clinicians, patient organisations and media.

Identifying Causative Mechanisms Linking Early-Life Stress to Psycho-Cardio-Metabolic Multi-Morbidity: The EarlyCause Project
Nicole Mariani, Alessandra Borsini, Charlotte A.M. Cecil, Janine F. Felix, Sylvain Sebert, Annamaria Cattaneo, Esther Walton, Yuri Milaneschi, Guy Cochrane, Clara Amid, Jeena Rajan, Juliette Giacobbe, Yolanda Sanz, Ana Agustí, Tania Sorg, Yann Herault, Jouko Miettunen, Priyanka Parmar, Nadia Cattane, Vincent Jaddoe, Jyrki Lötjönen, Carme Buisan, Miguel A. González Ballester, Gemma Piella, Josep L. Gelpi, Femke Lamers, Brenda WJH Penninx, Henning Tiemeier, Malte von Tottleben, Rainer Thiel, Katharina F. Heil, Marjo-Riitta Järvelin, Carmine Pariante, Isabelle M. Mansuy, Karim Lekadir
bioRxiv 2020.07.08.181958; doi:

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Epigenome-Wide Associations Between Observed Maternal Sensitivity and Offspring DNA Methylation: A Population-Based Prospective Study in Children

Dall’Aglio, Lorenza, et al. "Epigenome-wide associations between observed maternal sensitivity and offspring DNA methylation: a population-based prospective study in children." Psychological Medicine (2020): 1-11.

Experimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment.

These findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

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This project is funded by
Grant no. 848158

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