Assessing brain iron and its relationship to cognition and comorbidity in children with ADHD with quantitative susceptibility mapping (QSM).

Background: Quantitative susceptibility mapping (QSM) is a neuroimaging technique that detects local changes in magnetic susceptibility induced by brain iron. Brain iron and the dopaminergic system are linked since iron is an important cofactor for dopamine synthesis. ADHD is associated with dysregulation of dopaminergic transmission. Therefore, we applied QSM on subcortical structures, to study potential alterations in brain iron and its impact on cognition and mental health in children with ADHD.

Methods: 3 Tesla QSM-data of 111 participants (n_ADHD= 58, mean age: 13.2 (0.63); n_Controls=53, mean age: 13.2 (0.51)) were analyzed. Subcortical regional brain iron values were extracted. ANOVAs examined group differences for each region of interest. For dimensional approaches, Pearson correlation analysis was performed across the cohort examining the association with symptoms, mental health, and cognition.

Results: No significant differences were found in iron susceptibility between ADHD and control, between persistent and remitted ADHD, or between medication use. An unexpected finding was that children with internalising disorder had significantly higher iron susceptibility, but the result did not survive multiple comparison corrections. Higher brain iron was associated with sustained attention, but not on inhibition, IQ, and working memory.

Conclusion: This is the first study addressing brain iron susceptibility and its association with comorbidities and cognition in ADHD. Alterations in brain iron may not account for the full diagnosis of ADHD but may be an indicator of internalising problems in children. Alterations in brain iron content in children were linked to detrimental sustained attention and may represent developmental variation in cognition.