Children's internalizing behavior development is heterogeneously associated with the pace of epigenetic aging.

Background: Internalizing behaviors are an indicator of children's psychological and emotional development, predicting future mental disorders. Recent studies have identified associations between DNA methylation (DNAm) and internalizing behaviors. This prospective study aimed at exploring the associations between pace of biological aging and the developmental trajectories of internalizing behaviors.

Methods: Participants were children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N = 974). Measures of DNA methylation were collected at birth, age 7 and ages 15-17. The pace of aging was estimated using the DunedinPoAm algorithm (PoAm). Internalizing behaviors reported by caregivers between ages 4 and 16 using the Strengths and Difficulties Questionnaire. To explore heterogeneity in the association between PoAm and internalizing behaviors we use Poisson quantile regression in cross-section heterogeneity and longitudinal latent class analysis over the childhood and adolescence.

Results: Internalizing behavior trajectories were identified: low-risk, childhood limited, late onset and early onset (persistent). Accelerated aging at birth was negatively associated with internalizing behaviors in early childhood but positively correlated during adolescence. Higher PoAm at birth increased chance of low-risk profile, while decreasing likelihood of childhood limited trajectory. PoAm at age 15 was negatively associated with childhood limited profile and positively linked to late onset trajectories. Associations were larger at higher values of internalizing symptoms.

Conclusions: The heterogeneity in the association between biological age acceleration and internalizing behaviors suggests a complex dynamic relationship, particularly in children with high or increased risk of adverse mental health outcomes.