Serum selenium, iron and rubidium are altered in treatment-resistant schizophrenia

The molecular basis of schizophrenia is complex, involving an interplay of genetic and environmental factors. In recent postmortem and imaging studies, we identified disturbances in iron homeostasis in cortical and subcortical regions of individuals with schizophrenia. These may be relevant to neuropathology identified in the disorder and could relate to mechanisms of oxidative stress and inflammation. Recent work has proposed that there is a dysregulation of brain metals and other elements in schizophrenia that might impact on oxidative stress. Using a metallomics approach, we report robust changes in serum levels of pro-oxidant iron, anti-oxidant selenium, and the potassium-marker, rubidium, in a cohort of people with treatment-resistant schizophrenia (TRS). The cohort also expressed elevated levels of serum pro-inflammatory cytokines and hepcidin, and lower levels of anti-oxidant selenoproteins, selenoprotein-P1 (SEPP1) and glutathione peroxidase 3 (GPX3). The changes in serum iron, rubidium and selenium discriminate between control individuals and TRS cases, and they were not affected by age or clozapine serum levels. We propose that the changes in selenium and cytokines might drive the expression of hepcidin, resulting in reduced serum iron levels. Further research should investigate the relationship between peripheral and central measures of these elements and their metabolism, and further explore the relevance of pro-oxidant stress to the neuropathology of schizophrenia.