High circulating MIF levels indicate the association with atypical antipsychotic-induced metabolic adverse effects

Abstract Atypical antipsychotics (AAPs) are first-line medications for schizophrenia (SZ). However, their use is frequently associated with the development of metabolic adverse effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, we recruited 142 healthy individuals and 388 SZ patients who had been receiving either typical antipsychotic (TAP) or AAP treatments. Subsequently, we conducted assessments of metabolic indices and measured plasma MIF levels, followed by a comprehensive statistical analysis to investigate the connection between MIF levels and metabolic dysfunction. A significant increase in plasma MIF levels was observed in groups receiving monotherapies with five major AAPs in comparison to healthy controls (all p < 0.0001). There was no such increase shown in the group receiving TAP treatment (p > 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (β = 0.024, p = 0.020), as well as with the levels of triglycerides (β = 0.019, p = 0.001) and total cholesterol (β = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed some degree of metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, Plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Thus, MIF could be further developed as a unique marker to monitor AAP-induced metabolic adverse effects in clinical settings.