Multimodal Brain Age Indicators of Internalizing Problems in Early Adolescence: A Longitudinal Investigation

Adolescence is a time of increased risk for the onset of internalizing problems, particularly in females. However, how individual differences in brain maturation are related to the increased vulnerability for internalizing problems in adolescence remains poorly understood due to a scarcity of longitudinal studies.

Using ABCD (Adolescent Brain Cognitive Development) Study data, we examined longitudinal associations between multimodal brain age and youth internalizing problems. Brain age models were trained, validated, and tested independently on T1-weighted imaging (n = 9523), diffusion tensor imaging (n = 8834), and resting-state functional magnetic resonance imaging (n = 8233) data at baseline (mean_age = 9.9 years) and 2-year follow-up (mean_age = 11.9 years). Self-reported internalizing problems were measured at 3-year follow-up (mean_age = 12.9 years) using the Brief Problem Monitor.

Latent change score models demonstrated that although brain age gap (BAG) at baseline was not related to later internalizing problems, an increase in BAG between time points was positively associated with internalizing problems at 3-year follow-up in females but not males. This association between an increasing BAG and higher internalizing problems was observed in the T1-weighted imaging (β = 0.067, SE = 0.050, false discovery rate [FDR]-corrected p = .020) and resting-state functional magnetic resonance imaging (β = 0.090, SE = 0.025, p_FDR = .007) models but not diffusion tensor imaging (β = -0.002, SE = 0.053, p_FDR = .932) and remained significant when accounting for earlier internalizing problems.

A greater increase in BAG in early adolescence may reflect the heightened vulnerability shown by female youth to internalizing problems. Longitudinal research is necessary to understand whether this increasing BAG signifies accelerated brain development and its relationship to the trajectory of internalizing problems throughout adolescence.