Developmental Pathways From Genetic Predispositions to Psychopathology in Adolescence

J Am Acad Child Adolesc Psychiatry. 2026 May 19:S0890-8567(26)00230-3. doi: 10.1016/j.jaac.2026.05.008. Online ahead of print.

ABSTRACT

OBJECTIVE: Psychopathologies are interrelated and often co-occur, suggesting shared genetic and environmental influences. We examined the mediated associations between children’s genetic predispositions for higher-order psychopathology-represented by polygenic scores (PGS)-and the development of psychopathology symptoms from childhood to adolescence via baseline levels of psychopathology symptoms in childhood.

METHOD: We performed the same set of analyses in two longitudinal birth cohorts (Generation R Study, N= 4,657; ALSPAC, N= 4,368) and assessed the consistency of our results. PGS for externalizing, internalizing, and neurodevelopmental psychopathology were calculated using the LDpred2-automatic technique. Using growth curve modeling, we modeled the developmental slopes of child psychopathology symptoms into adolescence (ages 6 to 14-assessed by mothers using the Child Behavior Checklist [Generation R Study] and the DAWBA [ALSPAC]). We next performed three sets of mediation analyses (one per PGS) predicting the development of psychopathological symptoms via baseline levels (at age 6) of psychopathology during childhood.

RESULTS: The PGS for neurodevelopmental problems was linked to most baseline levels and developmental slopes of psychopathological symptoms through direct or mediated effects (i.e., via higher levels of symptomatology at baseline).

CONCLUSION: The PGS for neurodevelopmental problems could serve as a broad index of susceptibility to psychopathological symptoms in the general youth population.

STUDY REGISTRATION INFORMATION: Direct and Indirect Developmental Pathways From Genetic Predispositions to Mental Health Symptomatology in Adolescence; https://osf.io/hwv9a/.

PMID:42162606 | DOI:10.1016/j.jaac.2026.05.008