Experiences of childhood adversity are major risk factors for subsequent vulnerability to psychopathology. Although research suggests that specific brain regions are particularly sensitive to childhood adversity, the mechanisms that underlie these associations are yet to be elucidated and it is unclear how widespread connectivity networks contribute to this vulnerability phenotype. This project aims to determine the functional connectivity networks in the brain that bare the signatures of negative experiences and the genetic mechanisms that may facilitate such alterations. To achieve this, we propose two analyses utilizing data from the UK Biobank. Analysis 1 will investigate the resting state functional connectivity networks (rsfMRI) associated with early adversity. This study builds on previous results published by the applicant, and looking at early life stress associations with (structural) Imaging Derived Phenotypes in the UK Biobank dataset (Gheorghe et al., 2021, JCPP). Analysis 2 will characterize the inter-individual variations in adversity-related functional changes, by addressing the mediating effects of specific genetic variants that may increase biological vulnerability. Specific genomic associations of current interest have been previously reported in the UK Biobank, supporting the potential importance of these genetic variants for our epidemiological understanding of the adversity-brain relationship (Darvie et al., 2020, Translational Psychiatry). This research is supported by a Marie Curie Widera fellowship from the European Research Executive Agency, HORIZON-WIDERA-2022-TALENTS-02 (Project number: 101090316).
