Developmental Differences in White Matter Microarchitecture in Youth with ADHD: Longitudinal Findings from the ABCD...

Area of Science:

• Neuroscience
• Developmental Neuroscience
• Neuroimaging

Background:

• Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder.
• ADHD is a known risk factor for developing other brain disorders later in life.

Purpose of the Study:

• To investigate the relationship between ADHD and white matter cellularity across development.
• To examine the effects of ADHD medication on white matter characteristics.

Main Methods:

• Utilized a novel biophysical diffusion MRI model (Restriction Spectrum Imaging - RSI) in a large cohort (N=10,526) from the ABCD Study®.
• Analyzed 27 white matter tracts across three biennial MRI waves (ages 9-14) using longitudinal linear mixed-effect models.
• Quantified intracellular isotropic (RNI) and directional (RND) diffusion to assess white matter microstructure.

Main Results:

• ADHD was associated with decreased RNI in 20 tracts at age 9, showing developmental attenuation.
• Persistent ADHD-associated decreases in RND were observed in 16 tracts from ages 9 to 14.
• Methylphenidate showed effects on RND in 2 tracts; RNI findings were more robust.

Conclusions:

• ADHD is robustly linked to reduced isotropic diffusion in white matter, suggesting atypical glial cellularity in late childhood.
• Reductions in directional diffusion in select tracts may indicate atypical axonal organization persisting into early adolescence.