Immunoinflammatory Profile in Patients with Episodic and Continuous Paranoid Schizophrenia

Abstract

Introduction. Associations of disturbances in innate and adaptive immunity during the clinical course of schizophrenia have been found in a number of studies. Yet, the relationship of immune parameters and systemic inflammation in relation to the clinical course of the disease and its prognosis, remains poorly understood, which highlights an interesting topic for further research. The goal of this study was to research the immuno-inflammatory changes in patients with clinical continuous and episodic paranoid schizophrenia, to assess the pathogenetic significance of these changes.
 Methods. Thirty-six patients with paranoid schizophrenia, of which 20 had episodic symptoms and 16 had continuous symptoms, consented to participate in the study, together with 30 healthy volunteers. In the study we assessed the parameters of innate immune response (serum levels of key pro-inflammatory and anti-inflammatory cytokines, C-reactive protein) and the adaptive immune response, including humoral-mediated immunity (serum immunoglobulins IgA, IgM, IgG, circulating immune complexes), as well as the cell link of adaptive immunity (key lymphocyte subpopulations). Positive and negative symptoms were assessed with the positive and negative symptoms scale; frontal dysfunction was assessed by Frontal Assessment Battery (FAB).
 Results. Both patient groups had higher than normal levels of C-reactive protein and IL-8. There was a significant elevation of circulating immune complexes among patients with continuous symptoms of schizophrenia, compared to patients with episodic symptoms and healthy controls. Levels of CD45+CD3+ lymphocytes (T-cells) differed between clinical groups, with higher values identified among patients with episodic symptoms and lower values among those with continuous symptoms. In addition, patients with episodic symptoms had significantly increased levels of CD45+CD3+CD4+CD25+CD127- regulatory T-cells. Finally, the level of CD45+CD3-CD19+ B-cells was significantly higher among patients with continuous symptoms vs. patients with episodic symptoms and the control groups. Markers of activation of humoral immunity were associated with the severity of frontal disorders in these patients.
 Discussion. Comprehensive data on the serum level of cytokines and the parameters of adaptive immunity among individuals with continuous schizophrenia, by comparison with patients with episodic schizophrenia, are practically absent in the literature. We have shown that among those with continuous schizophrenia, there are signs of systemic inflammation and chronic activation of the adaptive humoral immune response, while among patients with episodic symptoms of the disease, there are signs of systemic inflammation and certain activation of cell-mediated immunity, without significant changes in the humoral link of adaptive immunity.
 Conclusion. More studies are needed, but the data obtained in this study are important for subsequent clinical studies of new treatment methods, based on various immunophenotypes of schizophrenia.

Cytokines as Potential Biomarkers of Clinical Characteristics of Schizophrenia

“…In a clinical sense, proinflammatory cytokines-as some of the pathogenesis components-play an important role in clinical polymorphism and the course of schizophrenia through reactivity mechanisms. Malashenkova et al [56] have reported that episodic schizophrenia and continuous schizophrenia have signs of systemic inflammation. At the same time, the continuous course of schizophrenia is characterized mainly by chronic activation of the humoral response, whereas the episodic one by some activation of cell-mediated immunity.…”

Identification of Diagnostic Schizophrenia Biomarkers Based on the Assessment of Immune and Systemic Inflammation Parameters Using Machine Learning Modeling

“…The literature and our data confirm the fact that patients with schizophrenia show the signs of systemic inflammation, which are most intensive in the first episode of the disease and in exacerbations. In disease exacerbation, the levels of pro-inflammatory cytokines IL-8, TNF-α, and CRP, an acute-phase protein, increase [18][19][20]. A high CRP level has been also shown to be associated with a more severe course of psychosis in schizophrenia and subsequent cognitive function decline [18,21].…”

“…Table 4 shows feature importance ranking using XGBoost classifier, having the second values of ROC AUC and ACC, high or moderate stability of the classification results (ROC AUC -0.68±0.21; ACC -0.75±0. 19).…”

The association of inflammatory status and immunological parameters with single-nucleotide polymorphisms of cytokine and Toll-like receptor genes in patients with schizophrenia

“…Numerous clinical, postmortem, biomedical, genetic and experimental studies, including cell and animal models, have shown that schizophrenia is accompanied by neuroinflammation and systemic immune disorders [4,5,6]. According to the results of large genome-wide association studies (GWAS), single-nucleotide polymorphisms in genes regulating the functions of the immune system have significant associations with schizophrenia risk [7,8]. Patients with psychotic episode have increased levels of inflammation markers in the cerebrospinal fluid and systemic circulation, and an increased expression of proteins involved in the immune response and inflammation in the prefrontal cortex [4][5][6][7].…”

“…According to the results of large genome-wide association studies (GWAS), single-nucleotide polymorphisms in genes regulating the functions of the immune system have significant associations with schizophrenia risk [7,8]. Patients with psychotic episode have increased levels of inflammation markers in the cerebrospinal fluid and systemic circulation, and an increased expression of proteins involved in the immune response and inflammation in the prefrontal cortex [4][5][6][7]. According to indirect evidence, schizophrenia associated with neuroinflammation can account for up to 40% of cases, but more convincing studies are needed [2].…”