# Deviation in development of dorsal association tracts during preadolescence links to concurrent and future cognitive performance and transdiagnostic psychopathology

## TL;DR

The study finds that deviations in brain white matter development during preadolescence are linked to cognitive performance and future psychiatric disorders.

## Contribution

The study introduces tract-specific brain age models to link white matter development to cognition and psychopathology.

## Key findings

- Deviations in association and limbic/subcortical white matter tracts correlate with current and future cognitive and psychiatric outcomes.
- Delayed brain age in dorsal association tracts predicts psychiatric disorders across diagnoses.
- The spatial pattern of association tracts aligns with high-order brain networks and mitochondrial maps.

## Abstract

Many psychiatric disorders begin during adolescence, coinciding with the rapid development of brain white matter (WM). However, it remains unclear whether deviations from normal WM development during this period contribute to psychopathology. In this study, we developed normative models of brain age based on specific WM tracts using three large-scale developmental datasets ( ~ 10,000 subjects). We found that tract-specific deviations in WM development of association and limbic/subcortical systems were linked to concurrent and future cognition and psychopathology. The spatial pattern of the association system aligned closely with high-order brain networks and mitochondrial maps. Importantly, delayed brain-age especially in dorsal association tracts predicted psychiatric disorders across diagnoses and disorder onset over a 2-year follow-up. By identifying tract-specific WM development during preadolescence as a predictor of cognitive capacity and psychiatric risks, this study provides a framework for tracking individualized brain development and understanding the neurobiological underpinnings of cognition and transdiagnostic psychopathology.

Using diffusion MRI data from over 10,000 youth, the authors develop 30 tract-specific brain age models and show that developmental deviations in association and limbic tracts are linked to concurrent and future cognition and psychiatric risks.