Macrophage migration inhibitory factor as a potential novel biomarker for cognitive function in patients with first-episode schizophrenia

Abstract

Objective: Cognitive impairment is prevalent in schizophrenia. Macrophage migration inhibitory factor which is released into the circulation under stress or inflammation, is associated with cognition and also plays an important role in immunity. However, no study has investigated the relationship between macrophage migration inhibitory factor and cognitive function in first-episode schizophrenia patients at baseline or after treatment. This study investigated the pre- and post-risperidone treatment correlations between serum macrophage migration inhibitory factor levels and cognitive function in first-episode schizophrenia patients. Methods: A total of 83 first-episode schizophrenia patients who received risperidone monotherapy and 57 healthy controls – matched for sex, age, smoking status, education (years), marital status and waist-to-hip ratio – were included. Macrophage migration inhibitory factor levels were measured before and 10 weeks after treatment in the patient group and at baseline in the controls. Pre- and post-treatment cognitive functions in patients were assessed using the MATRICS Consensus Cognitive Battery. Results: At baseline, macrophage migration inhibitory factor levels were significantly higher in first-episode schizophrenia patients than those in healthy controls ( p < 0.01) and decreased in patients after 10 weeks of risperidone treatment compared with baseline ( p < 0.05). The MATRICS Consensus Cognitive Battery total score and the sub-scores for the Trail Making Test, Symbol Coding, Letter Number Sequence, Maze and Brief Visuospatial Memory Test–Revised improved significantly after risperidone treatment. After controlling for age, sex, education, waist-to-hip ratio and smoking status, partial correlation analysis showed a positive correlation between baseline macrophage migration inhibitory factor levels and patients’ baseline MATRICS Consensus Cognitive Battery verbal memory scores ( r = 0.29, p = 0.01). Macrophage migration inhibitory factor changes correlated negatively with verbal memory changes ( r = −0.26, p = 0.04). Multiple linear regression analysis identified a definite correlation between the changes in word memory test score and macrophage migration inhibitory factor level (β = −0.09, p = 0.04). Conclusion: Macrophage migration inhibitory factor may be involved in the process of cognitive impairment in first-episode schizophrenia and repair mechanisms following risperidone treatment.

Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia

“…[26][27][28] Some articles have shown an association between elevated Hcy levels and cognitive dysfunction in patients with SP. 13,29,30 Specifically, the production of MIF is associated with longterm cognitive dysfunction of pneumococcal meningitis patients, 12 as well as cognitive dysfunction of patients with mild cognitive dysfunction or dementia. 31 These data are consistent with our current findings.…”

“…Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and a pluripotent key cytokine involved in immune response and physiological processes 11 . MIF mediates long-term cognitive dysfunction in bacterial meningitis, 12 and its changes are negatively correlated with verbal and wording memory changes 13 . Given reported associations between serum levels of hs-CRP, Hcy, and MIF and cognitive dysfunction, possible relationships between elevated levels of these inflammatory markers, cognitive function, and symptom severity were studied in first-episode, unmedicated patients with SP.…”