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Iron Deficiency Without Anemia and Reduced Basal Ganglia Iron Content in Youths
Dimitri Fiani1,2, Joo-Won Kim1, Mianzhi Hu3
1Baylor College of Medicine, Houston, Texas.
Insights
Iron deficiency without anemia in adolescents is linked to lower iron in basal ganglia, affecting brain structure and function, especially in females. This highlights the need to consider brain iron levels beyond simple blood tests.
Area of Science:
- Neuroscience
- Pediatric Medicine
- Radiology
Background:
- Brain iron is crucial for neurogenesis, myelination, and neurotransmitter synthesis.
- Iron deficiency (ID) is typically diagnosed solely by hematological markers.
- The impact of ID without anemia on brain iron content and function in adolescents is not well understood.
Purpose of the Study:
- To investigate the association between iron deficiency without anemia and basal ganglia (BG) iron content.
- To examine the structural and functional consequences of ID without anemia in the adolescent brain.
- To explore potential sex differences in these associations.
Main Methods:
- Cross-sectional study of 209 adolescents (aged 10-17) with or without psychiatric conditions, excluding anemia and acute inflammation.
- Iron deficiency without anemia defined as serum ferritin < 15 ng/mL.
- Brain magnetic resonance imaging (MRI) to measure BG susceptibility and volume; clinical interviews for psychiatric symptoms; neuropsychological testing.
Main Results:
- ID without anemia was associated with significantly lower iron content (susceptibility) in the caudate and putamen.
- A significant interaction between age and ID without anemia was observed in females, affecting caudate and putamen susceptibility.
- Lower BG iron content correlated with reduced BG structure volume, increased psychiatric symptom severity, and poorer neuropsychological performance, particularly in females.
Conclusions:
- Iron deficiency without anemia in adolescents is linked to reduced striatal iron content.
- This condition is associated with disrupted brain structure and function during a critical developmental period.
- Findings suggest that ID without anemia may have significant neurological implications, especially in adolescent females.
Importance:
Although brain iron is necessary for neurogenesis, myelination, and neurotransmitter synthesis, iron deficiency (ID) is defined solely based on hematological outcomes.
Objective:
To examine the association of ID without anemia with basal ganglia (BG) iron content and its structural and functional sequelae in adolescents.
Design, Setting, And Participants:
This cross-sectional study enrolled participants using the electronic medical record system from a large network of pediatrics clinics between December 2020 and April 2024. Otherwise healthy, unmedicated participants aged 10 to 17 years with a depressive or anxiety disorder or with no psychopathology were consecutively enrolled. Anemia and acute inflammation led to exclusion, and ID without anemia status was identified after procedure completion. Data were analyzed from May to November 2024.
Exposure:
Following the World Health Organization's guidelines, ID without anemia was defined as a serum ferritin concentration less than 15 ng/mL.
Main Outcomes And Measures:
Participants underwent a brain magnetic resonance imaging scan to measure BG susceptibility and structures volume, a clinical interview to rate psychiatric symptoms severity, and neuropsychological testing. Multivariable regression and correlational partial least-squares analyses examined the association of ID without anemia status and BG susceptibility with each other and with BG structures volume, psychiatric symptom severity, and neuropsychological performance.
Results:
Among a total of 209 participants (122 [58%] female; mean [SD] age, 13.5 [2.2] years; 62 participants [30%] with ID without anemia), ID without anemia was associated with a significantly lower susceptibility in the caudate (Cohen d = -0.41; 95% CI, -0.72 to -0.10; P = .01) and putamen (d = -0.38; 95% CI, -0.69 to -0.07; P = .02), after accounting for age and sex. Notably, in females, the age by ID without anemia status had a significant 2-way interaction, indicating larger difference in caudate (β = 1.11; 95% CI, 0.08 to 2.15; P = .04) and putamen susceptibility (β = 0.95; 95% CI, 0.18 to 1.71; P = .02) with increasing age, favoring those without ID without anemia. None of the 2-way interactions were significant in males. Moreover, BG susceptibility was inversely associated with BG structures volume and psychiatric symptom severity and positively associated with neuropsychological performance, particularly in female adolescents.
Conclusions And Relevance:
In this cross-sectional study, ID without anemia was associated with lower striatal iron content and disrupted structure and function during adolescence, a critical period when the brain develops and accrues iron, particularly in females.
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