Trace elements in schizophrenia: a systematic review and meta-analysis of 39 studies (N=5151 participants)

Context: The pathogenesis of schizophrenia appears to be multifaceted. Objective: The aim of this meta-analysis of studies that investigated blood and hair concentrations of trace elements in people diagnosed with schizophrenia was to determine whether levels of trace elements in patients with schizophrenia differ from those in healthy individuals. Data Sources: The PubMed, Scopus, and Web of Science databases were searched to January 2018. Study Selection: Studies that compared concentrations of trace elements in patients with schizophrenia with those in healthy controls, in patients with schizophrenia under different treatment regimens, or in patients with schizophrenia at different stages of disease were included. Data Extraction: Data on study and sample characteristics and measures of trace elements were extracted. Results: Thirty-nine studies with a total of 5151 participants were included. Meta-analysis of combined plasma and serum data showed higher levels of copper, lower levels of iron, and lower levels of zinc among patients with schizophrenia vs controls without schizophrenia. Subgroup analyses confirmed the following: higher levels of copper in plasma, in users of typical antipsychotic drugs, and in males; lower levels of zinc in serum, in patients in Asia, in drug-naive/drug-free patients, and in inpatients; lower levels of iron in serum, in patients in Asia, in drug-naive/drug-free patients, in patients on antipsychotic drugs, in inpatients, in patients with acute or newly diagnosed schizophrenia, in patients with chronic or previously diagnosed schizophrenia, and in males; and lower levels of manganese in plasma and in patients with chronic or previously diagnosed schizophrenia. Conclusions: This meta-analysis provides evidence of an excess of copper, along with deficiencies of zinc, iron, and manganese, in patients with schizophrenia.