Depression is a leading global disease burden. The spleen regulates iron homeostasis and systemic immunity, potentially influencing CNS function via the brain-spleen axis. Iron dysregulation may drive depression through oxidative stress, neurotransmitter imbalance, and neuroinflammation.
Research Questions
1.Is dysregulated iron metabolism associated with depression via brain-spleen axis dysfunction?
2.What multi-omics signatures characterize this pathway?
3.Does iron dysregulation causally contribute to depression via spleen-driven neuroinflammation?
Objectives
1.Compare Iron/Spleen Phenotypes: Assess spleen volume (MRI) and iron biomarkers (serum ferritin, transferrin) in depression vs. controls.
2.Construct Multi-omics Network: Integrate splenic iron, immune markers (CRP, cytokines), brain structure (MRI), and omics (genomics/proteomics) to model brain-spleen-immune interactions.
3.Test Causality: Perform Mendelian Randomization (MR) to evaluate causal effects of spleen iron metabolism on depression risk.
Scientific Rationale
1.Iron’s Dual Role: Essential for neurotransmission but neurotoxic in excess, promoting inflammation.
2.Brain-Spleen Axis: Preclinical evidence links splenic activity to depression via immune-brain crosstalk.
3.Knowledge Gap: No large-scale studies integrate genetics, iron biomarkers, and splenic/brain imaging to explain depression heterogeneity.
4.UK Biobank Utilization:The UK Biobank provides unique opportunities to explore these mechanisms at a population scale through its imaging-derived spleen phenotypes , genetic data, proteomics, metabolomics, and mental health measures.
Therefore, this project aims to assess the association and causal relationship between spleen iron metabolism and depression, and to construct integrated multi-omics immune regulation networks. The results will provide clinical evidence on the hypothesis of brain-spleen axis and identify the potential therapeutic targets for depression.