Brain iron concentration in childhood ADHD: A systematic review of neuroimaging studies

Iron deficiency may play a role in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). Due to its preponderant function in monoamine catecholamine and myelin synthesis, brain iron concentration may be of primary interest in the investigation of iron dysregulation in ADHD. This study reviewed current evidence of brain iron abnormalities in children and adolescents with ADHD using magnetic resonance imaging methods, such as relaxometry and quantitative susceptibility mapping, to assess brain iron estimates. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed for studies published between January 1, 2008 and July 7, 2023 in Medline, Scopus and Proquest. Regions of interest, brain iron index values and phenotypical information were extracted from the relevant studies. Risk of bias was assessed using a modified version of the National Heart, Lung, and Blood Institute quality assessment tool. Seven cross-sectional studies comparing brain iron estimates in children with ADHD with neurotypical children were included. Significantly reduced brain iron content in medication-naïve children with ADHD was a consistent finding. Two studies found psychostimulant use may increase and normalize brain iron concentration in children with ADHD. The findings were consistent across the studies despite differing methodologies and may lay the early foundation for the recognition of a potential biomarker in ADHD, although longitudinal prospective neuroimaging studies using larger sample sizes are required. Lastly, the effects of iron supplementation on brain iron concentration in children with ADHD need to be elucidated.