Brain iron concentrations in the pathophysiology of children with attention deficit/hyperactivity disorder: a
Alexia Degremont1, Rishika Jain1, Elena Philippou2
1Department of Nutrition and Dietetics, King's College London, London, UK.
Insights
Children with attention deficit/hyperactivity disorder (ADHD) may have lower brain iron levels. This systematic review suggests brain iron, not systemic iron, is more linked to ADHD pathophysiology in kids.
Area of Science:
- Neuroscience
- Pediatrics
- Biochemistry
Background:
- Attention deficit/hyperactivity disorder (ADHD) is a neurological disorder in children.
- Iron dysregulation is implicated in ADHD, with prior research focusing on systemic iron levels.
Purpose of the Study:
- To systematically review and compare iron concentrations (serum and brain) in children with ADHD versus healthy controls.
- To determine if brain iron content is a more reliable biomarker for ADHD than systemic iron.
Main Methods:
- A systematic literature search was performed across major databases (PubMed, Cochrane, Web of Science, Embase, Ovid) for studies published between 2000 and June 2019.
- Included studies measured mean differences in serum iron, serum ferritin, or brain iron between children with ADHD and healthy controls.
- Risk of bias was assessed using NIH quality assessment tools; Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
Main Results:
- Twenty case-control studies met the inclusion criteria.
- Inconsistent results were found for systemic iron levels: 10 of 18 studies showed differences in serum ferritin, and 2 of 10 in serum iron.
- Three studies assessing brain iron found significantly lower thalamic iron concentration in children with ADHD compared to controls.
Conclusions:
- Limited evidence suggests brain iron concentration, particularly in the thalamus, is more associated with ADHD pathophysiology in children than systemic iron levels.
- Further large-scale, longitudinal studies using magnetic resonance imaging are necessary to explore correlations between regional brain iron deficiency and ADHD symptoms.
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.
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