Although several underlying etiologic implications for schizophrenia (SZ) have been proposed, the cross talk between them is rarely explored systematically. The aim of the present study was to illustrate the pathogenic mechanism of SZ through describing a systematical pathophysiology network using proteomic signatures in first-episode SZ patients. A total of 3152 proteins were identified in leukocytes, and 475 of these proteins were significantly altered in SZ. Functional analysis revealed that cell redox homeostasis was dramatically disrupted, demonstrated as upregulated glycolysis, mitochondrial oxidative phosphorylation, and thioredoxin-centered antioxidant system. We also identified an activated complement system and caspase-independent apoptosis. In addition, increased pyruvate and lactate levels and decreased lactate-to-pyruvate ratios were observed in plasma of SZ patients. The results here lead to the hypothesis that increased oxidative stress is caused by metabolic upregulation and complement activation, which induces protein damage and cell apoptosis, thus contributing to the development of SZ. Antioxid. Redox Signal. 31, 579-588.
Keywords: immunity; metabolism; oxidative stress; proteome; schizophrenia.