Serum hepcidin / ferroportin levels in bipolar disorder and schizophrenia

J Trace Elem Med Biol. 2021 Dec;68:126843. doi: 10.1016/j.jtemb.2021.126843. Epub 2021 Aug 14.


Background: Despite several alternatives for cellular iron influx, the only mechanism for cellular iron efflux is ferroportin mediated active transport. In cases of ferroportin dysfunction, iron accumulates in the cell and causes ferroptosis. Hepcidin suppresses ferroportin levels and inflammatory activation increases hepcidin production. Mild inflammation in schizophrenia and bipolar disorder may alter hepcidin and ferroportin.

Methods: The study included a total of 137 patients aged 18-65 years, 57 diagnosed with schizophrenia and 80 with bipolar disorder, according to the DSM-IV diagnostic criteria, and a control group (HC) of 42 healthy individuals. Biochemical analyses, thyroid function tests, hemogram, serum iron level, iron-binding capacity, and ferritin levels were examined. Serum levels of hepcidin and ferroportin were measured with enzyme-linked immunosorbent assay (ELISA) method.

Results: A statistically significant difference was determined between the groups in terms of the serum ferroportin levels (F = 15.69, p < 0.001). Post-hoc analyses showed that the schizophrenia group had higher ferroportin levels than in the bipolar group (p < 0.001) and HCs (p < 0.001). Hepcidin levels did not differ between the groups. Chlorpromazine equivalent doses of antipsychotics correlated with ferroportin levels (p = 0.024).

Conclusion: Ferroportin levels were increased in the schizophrenia group, although iron and hepcidin levels were within normal ranges. Antipsychotics may alter the mechanisms which control ferroportin levels. Further studies are needed to examine the relationships between antipsychotics and iron metabolism for determination of causal relationship.

Keywords: Antipsychotics; Ferroportin; Hepcidin; Iron; Schizophrenia.

MeSH terms

  • Antipsychotic Agents* / therapeutic use
  • Bipolar Disorder* / blood
  • Bipolar Disorder* / drug therapy
  • Cation Transport Proteins
  • Hepcidins / blood
  • Humans
  • Iron
  • Schizophrenia* / blood


  • Antipsychotic Agents
  • Cation Transport Proteins
  • Hepcidins
  • metal transporting protein 1
  • Iron