The assumed carbonyl stress and cytokine pathophysiology focused on TNF mechanism and their changes during the clinical course of patients with schizophrenia. (A) Carbonyl stress pathway. (B) Pentosidine between schizophrenia at admission and controls. Fourteen patients with high pentosidine levels (>2 SDs greater than the mean in controls) are indicated by an asterisk. Values were compared with the two-tailed Mann–Whitney U test. Error bars indicate mean and SDs (15). (C) Pyridoxal levels between schizophrenia at admission and controls. (D) Correlation between the changes (Δ) in pyridoxal levels and in total scores (left) and positive symptom scores (right) on the brief psychiatric rating scale among the paired patients who showed a decrease in pyridoxal levels (18 cases) according to the clinical course (15). (E) Glycer-AGE, (F) sRAGE, and (G) the Glycer-AGEs/sRAGE ratio are compared between patients with schizophrenia and controls (18). (H) Microinflammation pathway. (I) Soluble TNF receptor 1, (K) adiponectin, and (L) PEDF levels between schizophrenia at admission and controls (19). (M) Low anti-inflammatory state as preparatory state in schizophrenia. (J) Microinflammation process in schizophrenia (19). Abbreviations: RCOs, reactive carbonyl compounds; GLO1 and GLO2, glyoxalase enzymes, glyoxalase 1 and 2; Glycer-AGE, glyceraldehyde-derived AGE; sRAGE, soluble AGE receptors; TNF, tumor necrosis factor; NO, nitric oxide; TNF-α, tumor necrosis factor-α; TNFR1, tumor necrosis factor receptor 1; TNFR2, tumor necrosis factor receptor 2; PEDF, pigment epithelium-derived factor; TACE, tumor necrosis factor-α converting enzyme; sTNF-α, soluble tumor necrosis factor-α; sTNFR1, soluble TNF receptor 1; sTNFR2, soluble tumor necrosis factor receptor 2. Reprinted with some modifications from Ref. (15), Copyright (2014), with permission from Oxford University Press (license number; 4242240961739) (20), Copyright (2015), with permission from Elsevier (license number; 4241901371993), and (21), Copyright (2017), with permission from Elsevier (license number; 4241910166222).