Project Summary/Abstract: Remotely Delivered Programs Targeting COVID-19 Stress-Related Depression and Substance Use The COVID-19 pandemic presents an unparalleled level of everyday stress and is likely to increase rates of depression and substance use, potentially overwhelming behavioral health treatment capacity. We have developed a new program (CHA MindWell; CHA-MW) to address the anticipated surge in demand for behavioral health services for our safety-net health system’s health system’s diverse and socioeconomically disadvantaged population. It has both a screening/monitoring/referral and an early intervention component: First, we implemented remote computerized adaptive testing (CAT-MH®) to stratify patients at risk of stress- related mental illness into 3 tiers: Minimal symptoms or low-risk (Tier 1), mild-to-moderate symptoms or at-risk but not meeting criteria for in-person treatment (Tier 2), and moderate-to-severe symptoms requiring treatment (Tier 3). In standard CHA-MW, CAT-MH is delivered online by email to participants monthly to determine if they are Tier 3 and referral to mental health treatment is needed. Second, Tier 2 patients are referred to a live, online psychoeducational program - Mindfulness-Based Cognitive Therapy for Resilience (MBCT-R), which is an 8-week group adapted from MBCT, which is effective for treatment of stress, anxiety, and depression (known risk factors for substance use), and preventing relapse among patients with recurrent depression. MBCT-R will therefore have impact both during and after COVID-19. When participants enroll in MBCT-R they receive enhanced CHA-MW (i.e., weekly in addition to monthly CAT-MH monitoring), allowing us to closely determine if a higher level of care becomes necessary. We will randomize Tier 2 patients who have mild-to- moderate symptoms of depression (CAT-Depression Inventory 50-75, PHQ-9 equivalency 10-20) in a 3-arm comparative effectiveness RCT to compare MBCT-R + enhanced CHA-MW weekly monitoring to either: a) enhanced CHA-MW weekly monitoring alone (with rapid referral to mental health treatment if needed), or b) an asynchronous internet CBT (iCBT) application + CHA-MW weekly monitoring. We expect MBCT-R to reduce depression symptoms (primary outcome), stress, and indirectly prevent substance use (secondary outcome). For a sub-study within the RCT, we will collect preliminary data using daily diaries to measure stress-related affective reactivity data (upticks in negative affect and/or reductions in positive affect during stress days) and adaptively sample salivary inflammatory cytokines (IL-6, TNF-a, IL-1b) remotely on 2 high and 2 low stress days before and after the interventions. Because this pragmatic effectiveness trial of a live, online mindfulness- based intervention with naturalistic remote monitoring is already embedded in our safety-net health system, it can be implemented immediately and disseminated rapidly if effective at reducing depression symptoms, and coul...