INTERGENERATIONAL PSYCHIATRIC GENETICS: LIABILITY AND EARLY-LIFE EXPOSURES ACROSS MATERNAL, CHILD, AND ADOLESCENT OUTCOMES

Overall Abstract Maternal, child, and adolescent health are deeply interconnected, with genetic liability, prenatal exposures, and early-life environments shaping trajectories of psychiatric, behavioral, and substance use outcomes across the lifespan. Pregnancy and early development represent sensitive periods during which maternal psychiatric conditions, reproductive health factors, and substance use exposures may influence maternal, child, and adolescent outcomes. Advances in psychiatric genetics and large-scale longitudinal cohorts now provide new opportunities to examine how genetic liability operates across developmental stages and generations. However, critical gaps remain in understanding how these factors jointly contribute to variation in outcomes from early life through adolescence and into adulthood. This symposium presents research integrating polygenic and data-driven approaches, including machine learning, to examine maternal, child, and adolescent health. Aditya Pimplaskar will present analyses integrating electronic health record and biobank data to examine clinical, social, and genetic liability for perinatal depression (PND). This work will highlight fair models within the UCLA health system and multi-site polygenic analyses in the PsycheMERGE consortium, relating PND to both non-perinatal major depressive disorder (MDD) and non-PND pregnancies. Dora Koller will present work characterizing multimorbidity trajectories for postpartum depression (PPD) in women with delivery records from the All of Us cohort, using latent class analysis to identify distinct pre- and post-delivery comorbidity profiles. Leveraging multimodal risk scores combining polygenic risk, obstetric complications, and socioeconomic factors in machine learning models, this work positions PPD as a pivotal event in women's long-term health trajectories. Fenfen Ge will present work examining heterogeneity in the polygenic architecture of attention-deficit/hyperactivity disorder (ADHD) across four developmental stages, from preschool through adulthood using iPSYCH and Danish Registries, highlighting how genetic liability for neurodevelopmental disorders may vary across the life course. Natasia Courchesne-Krak will present analyses leveraging polygenic scores for externalizing behaviors, including nicotine and cannabis use, demonstrating significant associations with maternal substance use in the Healthy Brain and Child Development (HBCD) Study, and examining how genetic liability and prenatal substance exposure jointly relate to sex-differentiated patterns of initiation, escalation, and comorbid substance use trajectories across adolescence in the Adolescent Brain Cognitive Development (ABCD) Study. Collectively, these studies demonstrate how genetic liability, prenatal exposures, and developmental processes jointly shape health trajectories across generations. By integrating EHR-based phenotyping, polygenic approaches, and longitudinal cohort data, this symposium highlights a framework for early identification, risk stratification, and prevention, with implications for precision medicine and health equity in psychiatric genetics.