Brain iron concentrations in the pathophysiology of children with attention deficit/hyperactivity disorder: a systematic review

CONTEXT: Attention deficit/hyperactivity disorder (ADHD) is a neurological disorder associated with iron dysregulation in children. Although previous focus was on examining systemic iron status, brain iron content may be a more reliable biomarker of the disorder. OBJECTIVE: This systematic review examines whether children with ADHD have lower serum as well as brain iron concentrations, compared with healthy control subjects (HCS). DATA SOURCES: A systematic literature search was conducted in Medline via PubMed, the Cochrane Library, Web of Science, Embase. and Ovid for papers published between 2000 and June 7, 2019. DATA EXTRACTION: Studies were included if the mean difference of iron concentration, measured as serum iron, serum ferritin, or brain iron, between children with ADHD and HCS was an outcome measure. DATA ANALYSIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Risks of bias within and between studies were assessed using the quality assessment tools of the National Institutes of Health. Of 599 records screened, 20 case-control studies met the inclusion criteria. In 10 of 18 studies in which serum ferritin concentration was assessed, and 2 of 10 studies that assessed serum iron, a significant difference between children with ADHD and HCS was observed. Results of systemic iron levels were inconsistent. In 3 studies in which brain iron concentration was assessed, a statistically significant, lower thalamic iron concentration was found in children with ADHD than in HCS. CONCLUSION: The evidence, though limited, reveals that brain iron rather than systemic iron levels may be more associated with the pathophysiology of ADHD in children. Larger, longitudinal, magnetic resonance imaging studies are needed to examine any correlations of iron deficiency in specific brain regions and symptoms of ADHD.