Retaining the diverse CANDLE cohort to advance ECHO Cohort solution-oriented research and identify early-life modifiable risk factors for obesity and mental health problems in children - Over 25% of children suffer from mental health problems and/or develop obesity. Mental health problems often emerge early through a broad range of symptoms before canalizing into disorders like depression, which affects over 15% of adolescents in the U.S. Risk for obesity also increases with age from 13% in early childhood to 22% in adolescence. Childhood diseases greatly impact adult health, and alarmingly, rates of child mental health problems and obesity are increasing, particularly for youth of color. Myriad early life risk and protective factors, often inequitably distributed and made more striking by the COVID-19 pandemic, have been associated with these outcomes; however, without large national samples and systematic identification of priority factors, clear targets for preventive interventions remain elusive. To address these critical issues, our interdisciplinary team leverages the unique power of ECHO Cohort data to conduct environment-wide scans for early life predictors of adolescent depression and obesity to identify and prioritize the most powerful targets for prevention, with a focus on sex-specific associations and improving causal inference (Aim 1). We also take a developmentally-informed, hypothesis-driven approach to understand the intergenerational relations between maternal childhood and pregnancy stress with childhood psychopathology risk, and if associations are sex- specific or buffered by family and community-level protective factors (Aim 2). To do this, we calculate a new, specialized neurodevelopmental outcome, the p-factor, which draws on multiple indicators of behavior and mental health to generate a single latent factor of general psychopathology in childhood and adolescence. This parsimonious, transdiagnostic measure is ideally suited for population-based child development studies that lack deep mental health phenotyping. Finally, we retain the socioeconomically and racially diverse CANDLE cohort (64% African American, 30% White; 700 mother-child dyads in the ECHO Program (Aim 3). Our success collecting ECHO Cohort data and contributions to diversity are self-evident: of the 69 ECHO cohorts, CANDLE ranks #1 in African American participants and #3 in records contributed to ECHO’s REDCap Central. Our team strongly contributes to collaborative science, leading multiple working groups, publishing and disseminating ECHO Cohort findings, supporting measurement development and data harmonization, and co- leading DEI efforts. Impact: We will generate robust evidence for prevention targets, including protective factors, to mitigate the public health impact of child mental health problems and obesity. We examine sex- specific associations and ensure that results are generalizable to youth of color, enhancing the potential of our findings to improve health equity. A transdiagnostic measure of pediatric psychopathology (p-factor) will be useful to many investigators and is well-suited to the examination of multiple exposures. The CANDLE study notably contributes to the diversity of the ECHO Cohort, and our experienced team’s continued leadership and partnerships during the next phase of ECHO will advance collaborative science to improve child health.