The Changes of Blood and CSF Ion Levels in Depressed Patients: a Systematic Review and Meta-analysis

Micronutrient deficiencies and excesses are closely related to developing and treating depression. Traditional and effective antidepressants include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and lithium. There is no consensus on the fluctuation of zinc (Zn²⁺), magnesium (Mg²⁺), calcium (Ca²⁺), copper (Cu²⁺), iron (Fe²⁺), and manganese (Mn²⁺) ion levels in depressed individuals before and after therapy. In order to determine whether there were changes in blood and cerebrospinal fluid (CSF) levels of these ions in depressed patients compared with healthy controls and depressed patients treated with TCAs, SSRIs, or lithium, we applied a systematic review and meta-analysis. Using the Stata 17.0 software, we performed a systematic review and meta-analysis of the changes in ion levels in human samples from healthy controls, depressive patients, and patients treated with TCAs, SSRIs, and lithium, respectively. By searching the PubMed, EMBASE, Google Scholar, Web of Science, China National Knowledge Infrastructure (CNKI), and WAN FANG databases, 75 published analyzable papers were chosen. In the blood, the levels of Zn²⁺ and Mg²⁺ in depressed patients had decreased while the Ca²⁺ and Cu²⁺ levels had increased compared to healthy controls, Fe²⁺ and Mn²⁺ levels have not significantly changed. After treatment with SSRIs, the levels of Zn²⁺ and Ca²⁺ in depressed patients increased while Cu²⁺ levels decreased. Mg²⁺ and Ca²⁺ levels were increased in depressed patients after Lithium treatment. The findings of the meta-analysis revealed that micronutrient levels were closely associated with the onset of depression and prompted more research into the underlying mechanisms as well as the pathophysiological and therapeutic implications.