Mediating Role of Trauma Connecting Psychiatric Family History and Adolescent Mental Health.

Background: Adolescent mental health is influenced by family history. Experiences of trauma also convey substantial risk for mental health challenges. Mediation of the association of family history with adolescent mental health by trauma experiences could be actionable and warrants evaluation. We sought to interrogate the mediating role of trauma in the association of family history of psychiatric disorders (FH) with adolescent general psychopathology, accounting for shared environment and genetics. Methods: The Philadelphia Neurodevelopmental Cohort was a cross-sectional study of participants ages 8 to 21 years with English fluency and in good medical health with characterization from November 2009 to December 2011. The analysis reported here was completed from March 2023 to February 2025. Among 7840 participants, we tested associations of first-degree FH (category count [0-4]: psychosis, mood, suicide attempt, substance use), youth exposure to trauma, neighborhood environment (block-level geocoded socioeconomic indices), and genomic factor of polygenic scores for psychopathologies (depression, posttraumatic stress disorder, schizophrenia, bipolar, cross-disorder) with adolescent general psychopathology modeled as p-factor. Association of FH with general psychopathology was assessed with structural equation modeling, querying for an indirect pathway via trauma, with stepwise accounting of genomics and shared environment, controlling for age and sex. Results: Of 7840 participants, 31% had FH and 44% of youths reported trauma exposure. Trauma had substantial direct association with general psychopathology and consistently mediated more than 20% of variance from FH to psychopathology, accounting for neighborhood and genomic predisposition. Conclusions: Trauma exposures mediate a substantial portion of association between FH and adolescent psychopathology, an opportunity for transgenerational intervention.