Early life stress (ELS) is a major risk factor for depression and two of its main physical comorbidities, coronary heart disease and diabetes. Some research suggests that depression develops from a complex interaction between biological and psychological processes. The EU-funded EarlyCause project will identify the biological contributions from four key interconnected domains: epigenetics, inflammation, neuroendocrine system and microbiome. It will take into account the effects of factors such as sex/gender, socioeconomics, lifestyle and behaviour. The project will combine basic, pre-clinical and clinical research, including causal inference methods, animal models of potential and postnatal stress, cellular models in various tissues, integrative bioinformatics and machine learning methods. The findings will deepen our understanding of biomarkers and innovation outputs in relation to new integrated care pathways.