PROJECT SUMMARY Effective emotion regulation (ER) requires the ability to flexibly and dynamically respond to affectively-valenced stimuli in the service of goal-directed behaviors. Patients with major mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD) are characterized by brain-based abnormalities in affective processing and cognitive deficits that make it difficult for them to regulate their emotions. Disruptions in ER are thought to play a role in risk for onset of illness, a relapsing course, and incomplete remission. Aging may amplify poor outcomes in older adults with depression, as reflected in a more severe course and treatment resistance. In contrast, in healthy adults, ER improves across the lifespan with a shift from attending to negative to attending to positive stimuli in attention, learning and memory. Consistent with RDoC, we will leverage multiple units of analysis (circuit, performance, self-report) in a transdiagnostic sample enriched for a range of ER-related network functions, implicit attentional biases, and ER strategies. We will enroll 200 adults (ages 41-80) with an affectively-stable mood disorder (100 BD, 100 MDD), and 100 demographically-matched healthy controls, allowing us to capture the range from extreme positive to extreme negative emotional experience. We will assess performance-based affective biases, cognitive control, and resting-state functional connectivity (FC), to define age-related changes in ER circuitry. We will assay habitual use of ER strategies, social functioning, and well-being to determine how brain-based processes affect these functionally- and clinically-relevant outcomes. Impact. The goals of this project are directly aligned with the NIMH Strategic Plan to develop new ways of characterizing and treating mental illness that are predicated on understanding brain-based mechanisms. Beyond the heuristic value of understanding the specific mechanisms and developmental trajectory of ER in mid and late life, results can be used to inform the development of novel interventions (e.g., neurostimulation, cognitive interventions) designed to “rescue” the specific network dysfunctions that give rise to maladaptive ER in depressive disorders.