Project Summary The most potent risk factor for the development of bipolar disorder (BP) is a first-degree family member with the illness; individuals with family history typically experience early BP onset and severe course. Up to 25% of offspring of parents with BP (OBP) develop BP by young adulthood. Using longitudinal data from the Pittsburgh Bipolar Offspring Study (BIOS MH60952), we developed a clinical tool (“risk calculator”) that reliably predicts an individual OBP’s 5-year risk for BP using a subset of demographic and clinical variables. This innovation offers the ideal opportunity to identify OBP at greatest risk and deliver indicated preventive interventions. Yet, to date, there is no evidence-based intervention for OBP who have not already developed mood disorder. Per the experimental therapeutics framework, promising approaches should be informed by, and target, factors that cause and sustain illness. Evidence suggests the pathway to develop BP among biologically vulnerable youth involves sleep and circadian disturbances. We adapted Interpersonal and Social Rhythm Therapy (IPSRT), an evidence-based treatment for BP adults that helps stabilize sleep/ circadian patterns, for adolescent OBP. In an open pilot and subsequent R34 randomized trial (MH091177), we established a preliminary efficacy signal for IPSRT with OBP. Our data further indicate IPSRT, but not Community Treatment Referral (CTR), engages and alters the hypothesized mechanism of action--sleep/ circadian disturbance, although practical barriers impacted treatment attendance. This proposal represents a vital next step in this program of research: a confirmatory efficacy trial of IPSRT delivered via telehealth for OBP (age 12-18, n=120) at elevated risk for BP onset via risk calculator score. All participants receive a baseline clinical assessment of psychiatric symptoms and sleep disturbance (via objective and subjective methods), followed by a feedback session. Youth are then randomized to receive 8 sessions of IPSRT or a manualized Healthy Lifestyle Behaviors Program (HL) delivered via secure videoconference to enhance attendance and reach. As clinically indicated, youth are offered CTR for any psychiatric symptoms/disorders identified at intake. Primary outcome domains over 18 months include subthreshold mania and affective lability--2 potent near-term predictors of BP in OBP that are themselves associated with morbidity and impairment. We will also further investigate the hypothesized mechanism underlying IPSRT-sleep/circadian disruption--across levels of analysis using reliable, cost-effective methods (actigraphy and daily diary ratings), and the contribution of interpersonal stress to sleep/circadian disruptions. Application of Implementation Science methods throughout maximizes ultimate scalability and feasibility if efficacious. We will also examine whether passive cellphone sensing may serve as a portable, cost-effective measure of mechanisms and outcomes to enhanc...