Population-based genetic and imaging studies of depression in adults have greatly advanced our understanding of this leading cause of global disability, particularly regarding associated neurobiological features. However, the causes and timings of such brain changes remain unknown, highlighting the need for a targeted study of the origins of these differences in younger individuals.

The largest risk factor for depression is a positive family history, and the major risk period for its development is during adolescence. The current project will therefore investigate whether the origin of these imaging features in adults (from work in UK Biobank, Enigma and Generation Scotland) is seen earlier in life in relation to increased risk for the disorder (including family history, polygenic risk, and associated traits such as depressive cognition, locus of control and self-esteem) using genetic and imaging data from children and parents in ALSPAC. Only now are there adult samples of sufficient size to inform such a focused study of adolescent depression, and this will form the first step towards determining potential causative associations between risk factors, associated neurobiology and depressive symptoms.

Summary data from these investigations in future could be combined in meta-analyses with other cohorts (e.g. MoBa) and consortia for discovery and replication. This would be under strict governance structures, where data would remain in Edinburgh and no individual data would be shared and this would be the focus of a separate application.