Identification of Biomarkers of Typical and Atypical Depression

Major depressive disorder is a highly polygenic disorder, with recent large genome-wide association studies identifying hundreds of common risk variants. There is also substantial variation in symptoms, severity and remission between individuals. It has been postulated that the heterogeneity observed in major depressive disorder is the result of several depression subgroups with differing aetiologies. One potential subgroup being atypical depression, which has been observed to differ from typical (or melancholic) depression in certain metabolic traits and weight changes during a depressive episode. Increasing the understanding of markers that differentiate between subtypes could provide more insight into the biological mechanisms underlying depression and improve treatment selection.

The project will investigate the genetic correlations of typical and atypical depression with psychiatric illnesses as well as metabolic and other related traits with the aim of identifying variables that discriminate between the subtypes. Initial analyses will include estimating the heritability of atypical and typical depression and a depression case-only genome-wide association study to identify risk variants associated with atypical depression. Later phenotype prediction models for atypical depression will be developed and tested. Differences in psychiatric and metabolic drug prescription and response will also be investigated between atypical and typical depression. All analyses will be performed in the UK Biobank or Generation Scotland population-based cohorts.