Iron Dysregulation and Neurobehavioral Outcomes

Iron is a trace element essential for cerebral function, participating in myelination, neurotransmitter synthesis and mitochondrial energetics. Its homeostasis within the central nervous system is governed by coordinated expression of transporters, storage proteins and regulatory hormones. Perturbations in iron balance, whether through deficiency or overload, can alter synaptic plasticity, redox signalling and neuronal integrity, leading to a range of neurobehavioral sequelae. Iron deficiency in early life has been linked to impaired cognitive development, attention deficits and mood disturbances, whereas excess iron accumulation in ageing and pathological conditions contributes to oxidative stress, vascular senescence and neurodegenerative processes. Genetic factors, inflammatory states and dietary influences modulate iron handling in the brain, creating a complex landscape in which regional iron deposits or systemic shortages exert far-reaching effects on memory, affect and reward circuitry. Clinically, this nexus underscores the importance of accurate assessment of iron biomarkers in individuals with psychiatric or cognitive impairments and points to intervention strategies such as tailored supplementation, chelation protocols or modulation of iron-related signalling pathways to preserve or restore neurobehavioral health.

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Iron Dysregulation and Neurobehavioral Outcomes publication trend

The graph below shows the total number of articles in iron dysregulation and neurobehavioral outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Hepcidin: A liver-derived peptide hormone that regulates systemic iron balance by inducing degradation of the iron exporter ferroportin.

Ferroportin: The only known cellular iron exporter, present on enterocytes and macrophages, whose degradation limits iron release into circulation.

Hypoxia-inducible factor (HIF-1α): A transcription factor stabilised under low oxygen or by prolyl hydroxylase inhibition, modulating genes involved in iron homeostasis and metabolism.

Endothelial senescence: A state of permanent cell cycle arrest in vascular endothelial cells, characterised by pro-inflammatory secretions and functional decline.

Soluble transferrin receptor (sTfR): A circulating form of the transferrin receptor reflecting cellular iron demand, used as a biomarker of iron deficiency.

References

1. Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis. Signal Transduction and Targeted Therapy (2023).
2. Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex‐dependent manner. Aging Cell (2023).
3. Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case–control study. European Journal of Nutrition (2024).