Stratifying Resilience and Depression Longitudinally (STRADL)

A single major depressive disorder diagnosis can mask dozens of different underlying conditions, and this project will use genetic and clinical data from 21,516 people to untangle them. Major depressive disorder (MDD) is not one illness but many, each with different causes, trajectories, and likely treatment responses. Current lumping of all patients together has stalled progress in understanding the biology of depression and developing targeted therapies. The researchers will first complete genome-wide association studies on the entire Generation Scotland cohort, then reassess participants with remote questionnaires and in-person follow-ups. From there, they will recruit individuals with quantifiable depression measures to test whether distinct subtypes—defined by clinical features, cognitive patterns, and neurobiological mechanisms—respond differently over time. A separate strand will investigate resilience: why some people exposed to the same stressors do not develop depression, and whether that protection can be measured and understood biologically. If successful, this work could shift depression from a one-size-fits-all diagnosis toward a stratified model where treatment is matched to subtype. That would mean fewer patients cycling through ineffective medications and a clearer path for developing drugs that target specific mechanisms. The resilience component could also inform preventive strategies for those at high risk.