Iron Deficiency Linked to Altered Brain Development in Adolescents, Even in Anemia Absence: JAMA

The study, conducted by Dr. Dimitri Fiani and colleagues from Baylor College of Medicine in Houston, Texas, and published in JAMA Network Open, explored how iron deficiency (ID) without anemia affects brain iron levels and related cognitive and psychiatric outcomes in adolescents.

Although iron is crucial for processes such as neurogenesis, myelination, and neurotransmitter production, ID is typically diagnosed using blood-based measures of anemia. This research focused instead on how ID—without the presence of anemia—might influence brain iron content, particularly in the basal ganglia, a region critical to motor control and cognitive function.

In this cross-sectional analysis, 209 otherwise healthy, unmedicated adolescents aged 10 to 17 years were enrolled between December 2020 and April 2024 through a network of pediatric clinics. The group included both adolescents with depressive or anxiety disorders and those without psychopathology. Participants with anemia or acute inflammation were excluded, and ID without anemia was defined by serum ferritin levels below 15 ng/mL, in line with WHO guidelines.

Participants underwent brain MRI scans to measure basal ganglia susceptibility—a marker of iron content—as well as clinical assessments of psychiatric symptoms and neuropsychological performance.

The study revealed the following findings:

• 30% of the adolescent participants had iron deficiency (ID) without anemia.
• These adolescents showed significantly lower iron content in the caudate and putamen regions of the brain.
• The reduction in brain iron content was more pronounced in females.
• The differences in brain iron levels appeared to increase with age, indicating a possible dose-dependent effect.
• In females, the interaction between age and ID status led to progressively larger differences in brain iron content over time.
• Lower basal ganglia iron content was associated with structural brain changes.
• Reduced iron levels were also linked to more severe psychiatric symptoms.
• Poorer cognitive performance was observed in adolescents with lower brain iron content, with stronger associations in females.

The authors note that this is one of the first studies to demonstrate that iron deficiency, even in the absence of anemia, can influence brain development during adolescence, a critical period for neurodevelopment.

However, the study’s cross-sectional design means the researchers could not determine when ID without anemia first developed in these individuals. They also call for future longitudinal studies to clarify how early-life ID might have lasting effects, to include more male participants, and to explore additional biomarkers beyond ferritin for better detection.

Given that certain racial and ethnic groups are more prone to ID, these findings highlight an urgent need to update clinical screening guidelines and proactively identify adolescents at risk, potentially preventing long-term neuropsychiatric consequences.

Reference:

Fiani D, Kim J, Hu M, et al. Iron Deficiency Without Anemia and Reduced Basal Ganglia Iron Content in Youths. JAMA Netw Open. 2025;8(6):e2516687. doi:10.1001/jamanetworkopen.2025.16687