PROJECT SUMMARY / ABSTRACT Suicide rates are high in late adulthood, peaking in midlife among women and late life among men. Social disconnection also peaks in late life and increases risks of suicide, persistent suicidality, and poor response to psychosocial interventions. Our proposal responds to RFA-MH-22-135, outlining the critical need to identify the mechanisms mediating the relationship between social disconnection and late-life suicidality and develop efficacious interventions to target these mechanisms. The proposed study leverages methodological and conceptual innovations, developed by our team, to investigate target engagement of the Positive Valence System (PVS) during a novel social reward psychotherapy for mid- and late-life suicidality. We designed Engage & Connect, a remotely delivered psychotherapy that targets social disconnection by increasing engagement in rewarding social activities. Engage & Connect aims to alter disturbances of the PVS that may underlie late-life suicidality. In this study, 128 adults aged 50-80 with major depressive disorder and suicidal ideation will be randomized to 9 weeks of Engage & Connect or Symptom Review and Psychoeducation (SRP) active control condition. We will measure PVS functions on brain and behavioral levels, through resting state functional connectivity of the PVS and behavioral changes in social reward responsivity using our novel validated STAR task (Social Task for Assessment of Reward). We will employ a cutting-edge “precision imaging” approach to estimate the functional brain map of each individual and track the longitudinal effects of treatment on PVS circuitry. Our rigorous methodological approach will allow us to test, at the individual level, the brain-based and behavioral mechanisms underlying response to psychotherapy that targets social disconnection. Identification of individual patients’ biological and behavioral profiles, linked with treatment response, can guide future psychotherapy personalization and increase its efficacy and reach to vulnerable older adults at risk of suicide.