TY - JOUR
T1 - Identifying causative mechanisms linking early-life stress to psycho-cardio-metabolic multi-morbidity
T2 - The EarlyCause project
AU - Mariani, Nicole
AU - Borsini, Alessandra
AU - Cecil, Charlotte A M
AU - Felix, Janine F
AU - Sebert, Sylvain
AU - Cattaneo, Annamaria
AU - Walton, Esther
AU - Milaneschi, Yuri
AU - Cochrane, Guy
AU - Amid, Clara
AU - Rajan, Jeena
AU - Giacobbe, Juliette
AU - Sanz, Yolanda
AU - Agustí, Ana
AU - Sorg, Tania
AU - Herault, Yann
AU - Miettunen, Jouko
AU - Parmar, Priyanka
AU - Cattane, Nadia
AU - Jaddoe, Vincent
AU - Lötjönen, Jyrki
AU - Buisan, Carme
AU - González Ballester, Miguel A
AU - Piella, Gemma
AU - Gelpi, Josep L
AU - Lamers, Femke
AU - Penninx, Brenda W J H
AU - Tiemeier, Henning
AU - von Tottleben, Malte
AU - Thiel, Rainer
AU - Heil, Katharina F
AU - Järvelin, Marjo-Riitta
AU - Pariante, Carmine
AU - Mansuy, Isabelle M
AU - Lekadir, Karim
PY - 2021/1/21
Y1 - 2021/1/21
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0245475
DO - 10.1371/journal.pone.0245475
M3 - Article
C2 - 33476328
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0245475
ER -
