University of Oulu

Mariani N, Borsini A, Cecil CAM, Felix JF, Sebert S, Cattaneo A, et al. (2021) Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity: The EarlyCause project. PLoS ONE 16(1): e0245475.

Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity : the EarlyCause project

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Author: Mariani, Nicole1; Borsini, Alessandra1; Cecil, Charlotte A. M.2,3;
Organizations: 1Kings Coll London, Inst Psychiat Psychol & Neurosci, Stress Psychiat & Immunol Lab, Dept Psychol Med, London, England.
2Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
3Univ Med Ctr Rotterdam, Dept Child & Adolescent Psychiat, Erasmus MC, Rotterdam, Netherlands.
4Univ Med Ctr Rotterdam, Generat R Study Grp, Erasmus MC, Rotterdam, Netherlands.
5Univ Med Ctr Rotterdam, Dept Pediat, Erasmus MC, Rotterdam, Netherlands.
6Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland.
7Univ Bristol, Bristol Med Sch, Integrat Epidemiol Unit, Med Res Council, Bristol, Avon, England.
8Imperial Coll London, Dept Metab Digest & Reprod Genom Med, Fac Med, London, England.
9IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Biol Psychiat Lab, Brescia, Italy.
10Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy.
11Univ Bath, Dept Psychol, Bath, Avon, England.
12Vrije Univ, Amsterdam UMC, Dept Psychiat, Amsterdam, Netherlands.
13Amsterdam Publ Hlth, GGZinGeest, Amsterdam, Netherlands.
14Amsterdam Neurosci Res Inst, Amsterdam, Netherlands.
15European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge, England.
16Erasmus MC, Dept Virosci, Rotterdam, Netherlands.
17Natl Res Council IATA CSIC, Inst Agrochem & Food Technol, Microbial Ecol Nutr & Hlth Res Grp, Valencia, Spain.
18Univ Strasbourg, Ctr Europeen Rech Biol & Med, Inst Genet & Biol Mol & Cellulaire, PHENOMIN ICS,CNRS,INSERM, Strasbourg, France.
19Oulu Univ Hosp, Med Res Ctr Oulu, Oulu, Finland.
20Univ Oulu, Oulu, Finland.
21Univ Pompeu Fabra, Dept Informat & Commun Technol, Barcelona, Spain.
22Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain.
23Univ Barcelona, Dept Biochem & Mol Biomed, Barcelona, Spain.
24Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
25Empir Commun & Technol Res, Bonn, Germany.
26Univ Barcelona, Dept Matemat & Informat, Barcelona, Spain.
27Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
28Oulu Univ Hosp, Unit Primary Hlth Care, OYS, Oulu, Finland.
29Brunel Univ London, Dept Life Sci, Coll Hlth & Life Sci, London, England.
30Univ Zurich, Med Fac, Zurich, Switzerland.
31Univ Zurich, Dept Hlth Sci & Technol, Lab Neuroepigenet, Brain Res Inst,Zurich Neurosci Ctr, Zurich, Switzerland.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
Persistent link:
Language: English
Published: Public Library of Science, 2021
Publish Date: 2021-04-28


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 the 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 shapes 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.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 16
Issue: 1
Article number: e0245475
DOI: 10.1371/journal.pone.0245475
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: This work is supported by the European Union’s Horizon 2020 research and innovation programme (grant n° 848158). The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
EU Grant Number: (848158) EarlyCause - Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity
Copyright information: © 2021 Mariani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.