Investigating the lifelong effects of early life stress on health
Stress experienced in the early stages of life – from pregnancy to adolescence – is common and pervasive, affecting up to 75% of pregnant women (and the unborn baby) and nearly 50% of children, with long term consequences for development and health. The EarlyCause project will study the hypothesis that early life stress (ELS), a well-established risk factor for depressive, cardiovascular and metabolic disorders individually, is a cause of multi-morbidity in these disorders.
The impact of early life stress in later life
Identifying Causative Mechanisms Linking Early-Life Stress to Psycho-Cardio-Metabolic Multi-Morbidity: The EarlyCause Project
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.
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: https://doi.org/10.1101/2020.07.08.181958