Multimodal brain age indicators of internalising problems in adolescence: A longitudinal investigation

Background: Adolescence is a time of increased risk for the onset of internalising problems, particularly in females. However, how individual differences in brain maturation relate to the increased vulnerability for internalising problems in adolescence remains poorly understood due to a scarcity of longitudinal studies. Methods: Using Adolescent Brain Cognitive Development (ABCD) Study data, we examined longitudinal associations between multimodal brain age and youth internalising problems. Brain age models were trained, validated, and tested independently on T1-weighted (T1; N=9523), diffusion tensor (DTI; N=8834), and resting-state functional (rs-fMRI; N=8233) MRI data at baseline (Mage= 9.9 years) and 2-year follow-up (Mage= 11.9 years). Self-reported internalising problems were measured at 3-year follow-up (Mage= 12.9 years) using the Brief Problem Monitor.Results: Latent change score models demonstrated that although brain age gap (BAG) at baseline was not related to later internalising problems, an increase in BAG between timepoints was positively associated with internalising problems at 3-year follow-up in females but not males. This association between an increasing BAG and higher internalising problems was observed in the T1 (β=0.071, SE=0.050, p=0.009) and rs-fMRI (β=0.091, SE=0.025, p=0.005) models but not DTI (β=-0.024, SE=0.053, p=0.648), and remained significant when accounting for earlier internalising problems. Conclusions: A greater increase in BAG over time may reflect the heightened vulnerability shown by female youth to internalising problems. Longitudinal research is necessary to understand if this increasing BAG signifies accelerated brain development and its relationship to the trajectory of internalising problems throughout adolescence.