Clinical evidence suggests that MBCT is an effective intervention to prevent relapse in major depression. The mechanisms underlying the positive effects of Mindfulness-Based Stress Reduction on different forms of human suffering have been studied extensively in healthy populations. However, little has been done to extend this research to study the neural and psychological mechanisms underlying the protective effects of MBCT in populations that are highly vulnerable to relapse. This project aims to (i) study the effects of MBCT on subjective experience and brain function in response to individually tailored emotional challenges; and (ii) develop objective brain biomarkers to accurately predict clinical status (sustained remission versus relapse) 6 months post-intervention. Thirty-six remitted patients with a history of recurrent depression will be randomly assigned to an 8-week intervention of either psychoeducation or MBCT. Clinical and behavioral measurements will be obtained pre and post-intervention; functional MRI assessments will be performed post-intervention. We predict that (i) MBCT (vs Psychoeducation) will reduce rumination triggered by self-referential emotional stimuli, while increasing awareness of evoked body-mind responses; (ii) these effects will be paralleled by overall changes in the relative activity balance between two ‘opponent’ brain networks, which support two different forms of self-referential processing (‘narrative’ vs ‘experiential’ self-focus); (iii) response differences in these networks between groups will enable accurate prediction of sustained remission versus relapse.