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ADHD symptom trajectories associated with grey matter reductions in Dutch NeuroIMAGE cohortDo ADHD symptoms change brain structure, and does getting better make those changes worse?

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Key Takeaway
Note associations between ADHD symptom trajectories and grey matter reductions in this observational cohort study.

This study utilized data from the longitudinal Dutch NeuroIMAGE cohort, which included individuals with ADHD and controls. The analysis encompassed three waves, with sample sizes of n=765 at Wave 1, n=644 from Wave 0 to 1, and n=149 from Wave 1 to 2. The primary outcome assessed grey matter development, specifically cortical thickness, surface area, and subcortical volumes.

cross-sectional results indicated that higher ADHD symptom counts were related to widespread reductions in surface area, most prominently in the frontal cortex. Additionally, smaller volumes were observed in the cerebellum, amygdala, and hippocampus among participants with more symptoms. Longitudinal analysis of the n=149 participants from Wave 1 to 2 showed that symptom improvement was associated with stronger reductions in surface area, particularly in prefrontal and occipital regions. Furthermore, this group exhibited more pronounced cortical thinning across multiple brain regions.

No safety data, adverse events, or tolerability information were reported in this study. The authors note that findings suggest an association between symptom trajectories and structural brain changes. Causality cannot be inferred from these observational data. The study did not report specific limitations, funding sources, or conflicts of interest. Clinicians should interpret these results as descriptive associations within a specific cohort rather than definitive evidence of disease progression or treatment effects on brain structure.

Imagine trying to understand how a garden grows while the weather changes. This study tracked individuals with ADHD and healthy controls through three waves of testing to see how their brains developed alongside their symptoms. Researchers looked at grey matter, which includes the brain's outer layer and inner structures. They found that at the first check-in, people with more ADHD symptoms had widespread reductions in surface area, especially in the frontal cortex, and smaller volumes in the cerebellum, amygdala, and hippocampus. These are areas involved in thinking, emotion, and memory. The study involved 765 people at the start, with 149 followed through the next wave. No safety issues were reported because the study tracked natural brain changes rather than testing a specific drug.

However, the most surprising finding came when looking at progress over time. When people showed symptom improvement between the first and second waves, their brains actually showed stronger reductions in surface area and more pronounced thinning in several regions. This might sound alarming, but the study only shows an association, not a cause-and-effect relationship. We do not know if the brain is changing because symptoms are improving, or if the brain is changing in a way that leads to symptom improvement. The data comes from a specific group in the Netherlands, so we cannot assume these results apply to every person with ADHD everywhere.

Think of these findings like a map showing that two roads often run together, but not necessarily because one built the other. The study highlights a complex connection between how symptoms move and how the brain develops. It does not mean that getting better is bad for your brain, nor does it mean the current understanding of ADHD is wrong. Instead, it invites us to look deeper at how brain growth and symptom levels interact in ways we are only beginning to understand. More research is needed to figure out exactly what is happening in the brain as people grow and their symptoms change.

What this means for you:
More ADHD symptoms linked to smaller brain areas, and symptom improvement linked to stronger reductions in surface area, but this shows association, not cause.

Study Details

Study typeCohort
Sample sizen = 765
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
Objective: While ADHD symptoms often decline from childhood into adulthood, the underlying neurobiological mechanisms, such as altered brain maturation or neural reorganization, remain incompletely understood. This study investigated how grey matter development relates to ADHD symptom trajectories into adulthood. Method: We analyzed data of individuals with ADHD and controls from the longitudinal Dutch NeuroIMAGE cohort, utilizing dimensional ADHD symptom scores (Conners Parent Rating Scale) from three waves and T1-weighted structural MRI scans from the final two waves. Using General Linear Models with permutation-based inference, we examined: 1) cross-sectional associations between ADHD symptoms and vertex-wise cortical thickness and surface area, and subcortical volumes at Wave 1 (n = 765, mean age = 16.95 years); and 2) longitudinal associations between symptom progression and brain morphometric changes (Wave 0 to 1: n = 644, mean age = 11.55-17.24 years; Wave 1 to 2: n = 149, mean age = 16.45-20.11 years). Results: Cross-sectionally, at Wave 1, more ADHD symptoms were related to widespread reductions in surface area, most prominently in the frontal cortex, and smaller volumes of the cerebellum, amygdala, and hippocampus. Longitudinally, symptom improvement from Wave 1 to Wave 2 was associated with stronger reductions in surface area, particularly in prefrontal and occipital regions, and with more pronounced cortical thinning across multiple brain regions. Conclusion: These findings suggest an association between symptom trajectories and structural brain changes, indicating that clinical improvement in ADHD behaviors might coincide with ongoing neural refinement during the transition to adulthood.
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