Variations in inflammatory regulators in male patients with chronic schizophrenia associated with psychopathology and cognitive deficits

Abstract

Background: Immune dysregulation has been identified as a contributing factor in the pathophysiology of schizophrenia. This study aimed to investigate variations in specific immune regulators and their correlation with psychopathology and cognitive functions in male patients with chronic schizophrenia.

Methods: Employing a cross-sectional design, this study included 72 male patients with chronic schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status were utilized to assess psychopathology and cognitive functions, respectively.

Results: Serum levels of interleukin (IL)-4, IL-10, IL-12p40, IL-13, and monocyte chemoattractant protein-1 (MCP-1) were measured. There were significantly increased levels of IL-4, IL-13, and MCP-1, alongside decreased levels of IL-10 in patients compared to controls (all P < 0.05). IL-4 levels showed a significant negative association with PANSS positive symptoms (beta=-0.222, P = 0.042). After controlling for antipsychotic medication, BMI, and smoking, this correlation was no longer significant (r=-0.232, P = 0.055). Additionally, positive correlations of IL-4 (beta = 0.297, P = 0.008), IL-13 (beta = 0.371, P = 0.001), and MCP-1 (beta = 0.280, P = 0.013) with language scores were observed. Increased levels of IL-4 (P = 0.044, OR = 1.994), IL-13 (P = 0.019, OR = 2.245), as well as IL-4 and MCP-1 interactions (P = 0.043, OR = 2.000) were positively associated with the risk of chronic schizophrenia, while lower levels of IL-10 (P = 0.003, OR = 0.2.867) were also linked to an increased risk.

Conclusion: The identified associations between specific immune markers and the clinical and cognitive features of chronic schizophrenia in males underscored the potential immune-mediated mechanisms underlying schizophrenia.

Keywords: Cognitive deficits; Immune dysregulation; PANSS; RBANS; Schizophrenia.

Fig. 1

Overview of the production of some cytokines. IL-4 is an adaptive cytokine primarily secreted by Th2 cells, mast cells, and eosinophils. IL-4 plays a pivotal role in regulating humoral immunity, promoting IgG and IgE production, enhancing the proliferation and differentiation of B cells, and suppressing Th1 cell-mediated inflammatory responses. IL-10 is a cytokine with extensive anti-inflammatory properties that is secreted by various cell types, including T cells, B cells, macrophages, and certain dendritic cells. IL-10 effectively inhibits the production of pro-inflammatory cytokines and limits autoimmune responses, thus playing a crucial role in maintaining immune tolerance and preventing immunopathological damage. IL-12 is produced by dendritic cells, macrophages, and certain B cells, and is essential for the differentiation and activation of Th1 cells. IL-12 is significant in anti-infective immune responses, particularly against intracellular pathogens, and promotes the recruitment and activation of natural killer cells and T cells. IL-13, with biological functions similar to IL-4, is predominantly produced by Th2 cells and contributes to regulating B cell function, enhancing antibody production, and balancing immune responses. (The figure was created using https://www.figdraw.com)

Fig. 2

Comparison of IL-4 (A), IL-13 (B), MCP-1 (C), and IL-10 (D) levels between schizophrenia patients and healthy controls (HC)

Fig. 3

Correlation of IL-4, IL-13, and MCP-1 with clinical symptoms and cognitive functions in schizophrenia patients. Positive correlations of serum IL-4, IL-13, and MCP-1 levels with language (A, B, C, respectively)