Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention
ABOUT THE PROJECT
Nearly 40% of the EU population each year suffers from a mental disorder. Adverse experiences early in life can produce important physiological changes, which become embedded biological traces leading to increased vulnerability for later depression. There is now robust evidence indicating that early metabolic challenges impinge upon energy balance regulatory systems, which, in many cases, overlap with stress-response systems. EMBED will identify informative DNA methylation differences associated with prenatal psychological and metabolic stressors in genes that are relevant for mood disorders. These will be related to shared biomarkers to define common biological substrates between early life stress and maternal obesity for prevention and treatment. We will also determine whether intervention strategies can reverse such epigenetic marks and related biomarkers. The relationship between DNA methylation pattern in human peripheral samples (cord blood) and brain will be studied in animal models and brain post-mortem samples from depressive patients. EMBED brings together leading researchers with complementary expertise to exploit existing clinical data sets, including biomaterial collections from previous collaborative proposals, that will be analyzed in an original and innovative way to study the role of different, but often co-occurring, adverse prenatal conditions on individual risk/resilience to develop mental disorders in adulthood. This research may lead not only to a better understanding of the risk architecture of major psychiatric disorders, but could also enable preventive measures in risk populations, new diagnostics and, potentially, therapeutic approaches since, in contrast to genetic variations, epigenetic effects on the transcriptome may be reversed, also in adulthood.
The primary objectives of this work are to:
- Assess shared epigenetic mechanisms of maternal stress and maternal obesity through DNA methylation analysis and discovery in children born to stressed or obese mothers as well as adult post-mortem brains from people whose mothers were stressed or obese;
- Test shared biological mechanisms mediating psychological stress and metabolic stress through metabolome and transcriptome analysis in two mother/infant cohorts;
- Define the epigenetic signature of disease reversibility;
- Delineate epigenetic signatures predicting high risk of depression for early prevention; and
- Discover novel genes that respond both to maternal stress and maternal obesity.
As secondary objectives, the project aims to also:
- Characterize the stability of methylation profiles of candidate genes between birth and later points in life; and
- Establish the level of correspondence in methylation profiles of genes between brain and peripheral white blood cells at birth and later in life.
This project is funded by UEFISCDI (contract 103, from 01.06.2019), through the ERA-NET COFUND-NEURON III (2018) grant call. For more details, please visit: https://uefiscdi.gov.ro/neuron-cofund