Identifying Causative Mechanisms Linking Early-Life Stress to Psycho-Cardio-Metabolic Multi-Morbidity: The EarlyCause Project
Author:
Mariani NicoleORCID, Borsini AlessandraORCID, Cecil Charlotte A.M.ORCID, Felix Janine F., Sebert Sylvain, Cattaneo AnnamariaORCID, Walton EstherORCID, Milaneschi YuriORCID, Cochrane Guy, Amid Clara, Rajan Jeena, Giacobbe Juliette, Sanz Yolanda, Agustí Ana, Sorg Tania, Herault Yann, Miettunen JoukoORCID, Parmar Priyanka, Cattane NadiaORCID, Jaddoe Vincent, Lötjönen Jyrki, Buisan Carme, Ballester Miguel A. GonzálezORCID, Piella GemmaORCID, Gelpi Josep L., Lamers Femke, Penninx Brenda WJHORCID, Tiemeier HenningORCID, von Tottleben MalteORCID, Thiel Rainer, Heil Katharina F., Järvelin Marjo-Riitta, Pariante CarmineORCID, Mansuy Isabelle M., Lekadir KarimORCID
Abstract
AbstractIntroductionDepression, 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 analysisThis 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 disseminationThe 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.
Publisher
Cold Spring Harbor Laboratory
Reference38 articles.
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