Regional Brain Age Deviations Reveal Divergent Developmental Pathways in Youth

Area of Science:

• Neuroscience
• Developmental Psychology
• Psychiatry

Background:

• Normative modeling quantifies deviations in brain maturation.
• Brain age gap (BAG) is a metric for neurodevelopmental deviations.
• Previous studies have not consistently identified BAG patterns across psychiatric disorders or examined its predictive power for developmental trajectories in youth's cognition and behavior.

Purpose of the Study:

• To investigate brain age gap (BAG) patterns in youth with ADHD.
• To explore BAG as a transdiagnostic indicator in psychiatric disorders.
• To determine if BAG can predict cognitive and behavioral developmental trajectories in adolescents.

Main Methods:

• Utilized longitudinal data from 9,074 adolescents (ages 9-15) from the Adolescent Brain Cognitive Development Study.
• Developed 8 region-specific brain age models using MRI data (volumes, thicknesses, surface areas) and the Brainnetome adolescent atlas.
• Employed multivariate linear regression for case-control and cross-sectional analyses, and joint latent-class mixed models for trajectory analysis.

Main Results:

• ADHD cases exhibited negative BAG in multiple brain regions (Cohen's d: -0.12 to -0.08).
• Subcortical BAG was a transdiagnostic indicator of younger-appearing brains (d: -0.07, p_fdr = 0.024).
• Widespread positive BAG predicted a trajectory towards internalizing behaviors, while negative BAG was linked to lower cognition and higher symptoms.

Conclusions:

• Integrating BAG with continuous cognitive and behavioral profiles provides a framework for early identification of atypical developmental trajectories.
• This approach may contribute to personalized medicine in child and adolescent psychiatry.
• BAG analysis offers a novel method for understanding neurodevelopmental variations in psychiatric conditions.