Assessing Brain Iron and Its Relationship to Cognition and Comorbidity in Children With Attention-Deficit/Hyperactivity Disorder With Quantitative Susceptibility Mapping.

Abstract

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

Methods: Quantitative susceptibility mapping data (3T) of 111 participants (n_ADHD = 58, mean [SD] age = 13.2 [0.63] years; n_Control = 53, mean [SD] age = 13.2 [0.51] years) were analyzed. Subcortical regional brain iron values were extracted. Analysis of variance was used to examine group differences for each region of interest. For dimensional approaches, Pearson correlation analysis was performed across the cohort to examine the association of brain iron with symptoms, mental health, and cognition.

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

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