In this presentation I will present data showing the relevance of environmental factors for the development of mental health problems and describe epigenetic factors which are mediating these effects. These include data from three projects, which combine genome-wide methylation analysis with functional neuroimaging studies and behavioural analyses in humans. Using this combined approach, we identified several differentially methylated regions, which are associated with brain activity during reward processing and behavioural inhibition, mediating risky substance use behaviour in adolescents.