Elevated Osteopontin and Interferon Gamma Serum Levels and Increased Neutrophil-to-Lymphocyte Ratio Are Associated With the Severity of Symptoms in Schizophrenia

Abstract

Inflammation and immune dysregulation could contribute to the pathogenesis of schizophrenia. Osteopontin (OPN) is a cytokine-like glycoprotein involved in inflammation and in modulating immune responses, and it can also directly modify the cytokine expression and survival of microglia. Furthermore, elevated gene expression of OPN in first episode psychosis has recently been described, but to date OPN level has not been investigated in schizophrenia. Imbalance of T-helper subtypes could also represent a vulnerability factor for schizophrenia. In this study, we analyzed the concentration of OPN, levels of cytokines associated with T-helper subtypes: interferon gamma (IFNy) for Th1, interleukin (IL)-10 for Th2, IL-8 for Th17, and neutrophil-to-lymphocyte ratio (NLR) in 22 patients with schizophrenia assessed for the intensity of their symptoms by the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale (CGI) scores. Serum OPN, IFNy, IL-10, and IL-8 concentrations were measured by ELISA kits and NLR was calculated from blood count. We found significant correlation between the level of OPN and PANSS-total and PANSS-general scores. IFNy level and NLR showed significant correlation with PANSS-total, PANSS-positive, PANSS-general, and CGI score. Among the measured markers antipsychotic therapy only had significant effects on NLR and OPN level, both of which were significantly reduced after long-term antipsychotic treatment. Our results indicate that elevated OPN and IFNy concentrations, and increased NLR are associated with severe symptoms in schizophrenia and suggest the importance of Th1 subtype in patients with high PANSS-positive and PANSS-general subscore. Significant correlation between NLR and PANSS scores strengthens the inflammation hypothesis of schizophrenia.

Mechanisms of interactions between lung‐origin telocytes and mesenchymal stem cells to treat experimental acute lung injury

“…To further define the effective direction between MSCs and TCs, the migration capacity of MSCs was investigated in the co‐culture of MSCs with TCs under the condition of either MSCs OPN– or TCs OPN– or both. Figure 7G demonstrated that OPN contributed to the infiltration of MSCs, and OPN from activated TCs could influence MSCs even more, similar to the finding that external OPN increased survival, proliferation, migration, and differentiation of neural stem cells at a dose‐dependent pattern 29 . OPN from MSCs or TCs played a decisive role in dynamic proliferation and movement of MSCs (Figure 7H).…”

“…Figure 7G demonstrated that OPN contributed to the infiltration of MSCs, and OPN from activated TCs could influence MSCs even more, similar to the finding that external OPN increased survival, proliferation, migration, and differentiation of neural stem cells at a dose-dependent pattern. 29 OPN from MSCs or TCs played a decisive role in dynamic proliferation and movement of MSCs ( Figure 7H). OPN from TCs played more important role in support of MSCs proliferation, and activated TCs could maintain dynamic proliferations of MSCs OPN-, while MSC OPN+ proliferation was lower when co-cultured with TCs OPN- (Figure 7H1).…”

Is Elevated Neutrophil Count and Neutrophil-to-Lymphocyte Ratio a Cause or Consequence of Schizophrenia?—A Scoping Review

“…Moreover, four of five studies found positive correlation between PANSS total score and neutrophil count or NLR. Of note, in the study that did not report correlation with PANSS (30), the patients had lower total symptoms burden than the patients in the other studies (21)(22)(23)26). This indicates that the neutrophil numbers and NLR may be a state marker for disease severity or disease phase in schizophrenic patients, rather than an effect of antipsychotics.…”

“…Six studies investigated the effect of antipsychotics on neutrophil numbers ( Table 3 ). Three studies had longitudinal measurements ( 25 , 26 , 31 ), the others were cross-sectional ( 21 , 24 , 27 ). One study included a comparison based on antipsychotic response ( 25 ).…”

“…Four studies revealed a significant association between neutrophil status and PANSS-total [Table 3; (21)(22)(23)26)], and this was driven by a positive correlation with PANSS-P but not PANSS-N.…”