Stratifying Resilience and Depression Longitudinally (STRADL) (360G-Wellcome-104036_Z_14_Z)

Progress in understanding the pathophysiology of MDD has been severely restricted by its aetiological heterogeneity. Our contention is that longitudinal and quantitative assessment of individuals stratified by key exposures and course modifiers will reduce dilution across diverse aetiologies, measurement error and capture more of the total phenotypic variation. It will thus enable the mechanisms underlying resilience, depressive symptoms and MDD to be determined. Our goal is to utilise an ex isting cohort of 21,516 individuals extensively phenotyped for MDD and related quantitative traits called Generation Scotland . We will initially reassess this cohort using remote questionnaires and further assessments in the first year of STRADL, whilst completing GWAS on the entire sample. After conducting our baseline assessments, we will then recruit individuals with quantifiable measures of MDD to test key hypotheses about the heterogeneity of MDD. Specifically we will address the follo wing aims: 1. Identify subtypes of MDD and define their discriminating clinical features, cognitive characteristics and neurobiological mechanisms 2. To test for distinct mechanisms, clinical trajectories and treatment responses in these MDD subtypes 3. To test whether resilience can be constructed and quantified 4. To identify the neurobiological mechanisms underlying resilience to MDD