B3758 - EMBED - 07/04/2021

B number: 
Principal applicant name: 
Robi Tacutu | Institute of Biochemistry of the Romanian Academy (Romania)
Prof. Moshe Szyf
Title of project: 
Proposal summary: 

Around 40% of the EU population suffers from a mental disorder. Healthy development can be derailed by excessive or prolonged activation of stress response systems in the body and brain during fetal life. Such toxic stress exposure can have damaging effects on learning, behavior, and mental health across the lifespan. Our ERA-NET consortium (Project EMBED) focuses on two cohorts (offspring of obese or stressed mothers), aiming to address specific questions on mental health risk factors. This might be then used in the clinic for disease prevention and health promotion during pregnancy.

Our hypothesis is that maternal obesity and inadequate nutrition during prenatal life can trigger similar responses to maternal stress, altering developmental trajectories and increasing the risk for mental health in adulthood. These adverse experiences can increase the likelihood of developmental delays and later health problems.

Our consortium analyzes epigenetic modifications from the abovementioned cohorts, assessing whether common biological signals characterize early exposure to metabolic and psychological stress, affecting the long-lasting expression and methylation of genes involved in depression, obesity, and immune-metabolic function. We propose to use the ALSPAC data to compare and validate the findings from our consortium-generated data, in a larger/complementary context.

Impact of research: 
Major depression constitutes an enormous medical, individual, societal and economical challenge (depression afflicts up to 10-15% of the population worldwide). Despite extensive investigations, the exact mechanisms responsible for depression have not been identified, and current therapeutics are based on serendipitous discoveries rather than on bench-to-bedside, targeted drug discovery. In addition, although clinically efficient antidepressant drugs do exist, they show high treatment-resistance rates, slow onset of action, side effects, and drug–drug interactions. Currently, there is a clear consensus that early adverse experiences can impinge upon stress/metabolic pathways to coordinate body responses, increasing adult individual susceptibility for mental disorders such as depression. By carrying out the EMBED project, the consortium aims to advance this field of research by studying in more depth the links between pre-natal stresses and post-natal epigenetic modification, and by doing so, potentially enable preventive measures in risk populations, new diagnostics and new therapeutic approaches - for example by nutritional strategies reducing neuroinflammatory mechanisms implemented in the offspring.
Date proposal received: 
Friday, 2 April, 2021
Date proposal approved: 
Wednesday, 7 April, 2021
Mental health - Psychology, Psychiatry, Cognition, Mental health, Obesity, Computer simulations/modelling/algorithms, Statistical methods, major depression, mental disorders, obesity, prenatal, metabolic stress, psychosocial stress