Abstract
Dysregulation of the type 17 immune pathway has already been considered in schizophrenia and we previously measured decreased sera values of interleukin (IL)-17 in early stages. We further explored the possible correlation of IL-17 systemic levels with proinflammatory cytokines and cognitive scores and additionally analyzed the percentage of IL-17 producing lymphocytes in peripheral blood of patients with stable schizophrenia. We included 27 patients diagnosed with schizophrenia (F20), after a three-month stable depot antipsychotic therapy (risperidone or paliperidone) and 18 healthy control subjects. Positive and Negative Syndrome Scale of Schizophrenia and the Montreal-Cognitive Assessment (MoCA) were conducted. Sera concentrations of IL-17, IL-6, tumor necrosis factor alpha (TNF-α) and soluble ST2 receptor (sST2) were measured. Flow cytometry and Natural Killer (NK) and T cell analyses were done in 10 patients and 10 healthy controls. Moderate positive correlation was established between IL-17 and TNF-α (r = 0.640; p = 0.001), IL-17 and IL-6 (r = 0.514; p = 0.006), IL-17 and sST2 (r = 0.394; p = 0.042). Furthermore, a positive correlation between the serum levels of IL-17 and MoCA scores was observed, especially with visuospatial and executive functioning, as well as language functioning and delayed recall (p < 0.05). Significantly higher percentage of IL-17 producing CD56+ NK cells was measured in peripheral blood of patients with schizophrenia in remission vs. healthy individuals (p = 0.001). The percentage of CD4+ T cells and CD4+ T cells that produce IL-17 was significantly increased in patients (p = 0.001). This study revealed the involvement of innate type 17 immune response in the progression of inflammation and this could be related to cognitive functioning in stable schizophrenia.
Highlights
In the last half of the century, many biomarker candidates in mental disorders have been described.They could be applicable as a trait marker in establishing diagnosis, as a state marker in exacerbation or even in predicting the treatment response and outcome [1]
It has been speculated that IL-17 affects tight junctions between endothelial cells in the blood–brain barrier, allowing Th17 cells, one of the main sources of IL-17, to enter and accumulate in the central nervous system (CNS) [30]
Our results revealed a positive correlation between serum levels of IL-17 and Montreal-Cognitive Assessment (MoCA) scores in the examined patients, suggesting its moderate impact on global cognitive functioning and strong influence on visuospatial and executive functioning, as well as language functioning and delayed recall
Summary
In the last half of the century, many biomarker candidates in mental disorders have been described. They could be applicable as a trait marker in establishing diagnosis, as a state marker in exacerbation or even in predicting the treatment response and outcome [1]. The heterogeneous data about state and trait markers could reflect the core problem of the schizophrenia concept, representing a combination of syndromes rather than a single clinical entity. Some authors suggested that it could be useful to subdivide this population of patients with schizophrenia into more homogenous subgroups for cytokine measuring and study combinations of biomarkers, including immune signatures [4]
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