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

Abstract

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.

Keywords: Adolescent; Family history; General psychopathology; Neighborhood; Polygenic scores; Trauma.

Figure 1

Proposed pathway analysis of p-factor. Structural equation modeling was applied to estimate the total effects of family history of psychopathology on adolescent mental health (p-factor) with a mediating pathway via trauma. Further models incorporated the effects of neighborhood environment and latent genetic factor represented by polygenic scores for psychiatric conditions. Covariates not shown include age and sex.

Figure 2

Model 3. Effect of latent genetic factor on p-factor in EUR-like cohort. (A) Path diagram with standardized path coefficients, where ( ) indicates insignificant (p > .05) coefficient. Regression relationships between variables are depicted as one-headed arrows pointing from the independent variable to the dependent variable. Rectangular variable outlines indicate measured variables, and ovular variable outlines indicate latent constructs. (B) Model details: For each hypothesis and path, unstandardized (path) coefficients with 95% CIs and Wald statistic (T) values are reported. Models controlled for age and sex. Estimator: MLR; optimization method: NLMINB; number of model parameters = 20; number of observations = 4890. Adjusted χ²₃₆ = 196.31, p < .001. Post hoc power analysis with RMSEA = 0.03, n = 4890, model df = 36, alpha = .05 indicates a high-powered analysis; power > 0.999. BIP, bipolar disorder; CDG, cross-disorder group; EUR, European; FH, family history of psychopathology; MDD, major depressive disorder; MLR, maximum likelihood robust; NLMINB, nonlinear minimization subject to box constraints; PGS, polygenic score; PTSD, posttraumatic stress disorder; RMSEA, root mean square error of approximation; SCZ, schizophrenia.