Major depressive disorder (MDD) and bipolar disorder (BD) are prevalent and disabling psychiatric disorders, often following a chronic and relapsing course. The Collaborative Research Centre 393 (SFB/TRR 393), funded by the German Research Foundation (DFG), aims to identify trajectories and symptom changes in MDD and BD, with a focus on cognitive-emotional mechanisms and their neurobiological underpinnings.Our research initiative seeks to (1) identify individual trajectories of recurrences and remissions in affective disorder (AD), (2) determine cognitive-emotional mechanisms and neurobiological correlates of acute symptom changes, and (3) probe mechanism-based interventions.These goals will be pursued through a threefold approach: (1) Continuous mobile assessment in a prospective cohort: We will combine in-depth clinical characterization with multilevel neuroimaging, biobanking, and -omics analyses in 1500 AD patients and healthy participants over a 2-year follow-up (German Mental Health Cohort, GEMCO) at three time points. Participants will be drawn from existing DFG FOR 2107 and BMBF Early-BipoLife cohorts (Domain A). (2) Identification of key cognitive-emotional mechanisms: We will study emotion regulation, expectation, social cognition, and cognitive-behavioural rhythms, and their neurobiological correlates mediating symptom changes, using parallel human studies and animal experiments (Domain B). (3) Targeted interventions: We will probe key cognitive-emotional mechanisms in relation to recurrences and remissions (Domain C).Over a 12-year period, we will elucidate environmental, psychosocial, and (neuro)biological predictors of illness course; cognitive-emotional and neurobehavioural mechanisms underlying real-life recurrences and remissions; and targeted, mechanism-based interventions.