Altered MANF and RYR2 concentrations associated with hypolipidemia in the serum of patients with schizophrenia.

Schizophrenia (SCZ) is associated with abnormal serum lipid profiles, but their relationship is poorly understood. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an important regulator of lipid metabolism. Previous studies have shown its involvement in the pathogenesis of numerous neuropsychiatric disorders, while its role in SCZ is still unknown. Therefore, this study was conducted to examine serum MANF levels in patients with SCZ, and to investigate the potential relationship between MANF, serum lipid levels and SCZ. The results showed that total cholesterol (TC) levels were significantly lower in 225 patients with SCZ than in 233 healthy controls (HCs). According to Ingenuity Pathway Analysis, hypolipidemia is associated with SCZ via MANF/ryanodine receptor 2 (RYR2) pathway. This theory was supported by another sample set, which showed significantly lower MANF levels and higher RYR2 levels in the serum of 170 SCZ patients compared to 80 HCs. Moreover, MANF and RYR2 levels both were significantly correlated with the severity of psychotic symptoms and TC levels. In addition, a model consisting of MANF and RYR2 was found to be effective in distinguishing SCZ patients from HCs. These findings suggested that the MANF/RYR2 pathway might serve as a bridge between hypolipidemia and SCZ, and MANF and RYR2 held promise as biomarkers for SCZ.