Regional brain age deviations reveal divergent developmental pathways in youth

Area of Science:

• Neuroscience
• Developmental Psychology
• Psychiatry

Background:

• Normative modeling quantifies deviations in brain development.
• Brain age gap (BAG) measures individual neurodevelopmental deviations.
• Previous studies have not explored BAG's predictive power for youth's cognitive and behavioral trajectories across psychiatric disorders.

Purpose of the Study:

• To investigate brain age gap (BAG) patterns in psychiatric disorders.
• To determine if BAG can predict cognitive and behavioral trajectories in youth.
• To establish a normative framework for identifying atypical neurodevelopment.

Main Methods:

• Utilized longitudinal data from the Adolescent Brain Cognitive Development Study (n=9,074, ages 9-15).
• Developed 8 region-specific brain age models using MRI data (volumes, thicknesses, surface areas).
• Employed multivariate regression and joint latent-class mixed models to analyze psychiatric diagnoses, cognitive/behavioral profiles, and developmental trajectories in relation to BAG.

Main Results:

• Children with ADHD exhibited delayed maturation across multiple brain regions (Cohen's d: -0.12 to -0.08).
• Subcortical BAG served as a transdiagnostic indicator of delayed development (d: -0.07, p_fdr = 0.024).
• Accelerated maturation correlated with high cognition and low symptom profiles, while delayed maturation was associated with low cognition; widespread accelerated maturation predicted internalizing behaviors and protected against externalizing behaviors.

Conclusions:

• Integrating BAG with continuous cognitive and behavioral data provides a framework for early identification of atypical developmental trajectories.
• This approach has the potential to advance personalized medicine in child psychiatry.
• The findings highlight the utility of BAG as a normative metric for understanding neurodevelopmental variations.