The relationship between inflammatory biomarkers and cognitive dysfunction in patients with schizophrenia: A systematic review and meta-analysis

Background: Schizophrenia is a complex psychiatric disorder that includes positive and negative symptoms but also debilitating cognitive deficits. Current pharmacological interventions do not target these deficits. Recent evidence suggests a connection between some inflammatory markers (including C-reactive protein) and cognitive impairment, but did not address other inflammatory markers. In the current study, we try to fill the gap by focusing on the association of Interleukin-6 (IL-6), IL-113, Tumor Necrosis Factor-alpha and CRP with cognitive dysfunction.Methods: PUBMED and Web of Science databases were searched for all studies published until July 2022. A total of 25 studies were included in an analysis of the association between cognitive performance and variation in IL-6, IL-113, TNF-alpha and CRP.Results: A total of 2398 patients were included in this study. Meta-analyses results showed a significant inverse relationship between performance in five cognitive domains (attention-processing speed, executive function, working memory, verbal and visual learning and memory) and systemic IL-6, IL-113, TNF-alpha and CRP plasma levels in patients with schizophrenia. The meta-analyses results showed a significant decline in the cognitive perfor-mances with the evaluated inflammatory markers with effect sizes ranging from-0.136 to-0.181 for IL-6,-0.188 to-0.38 for TNF-alpha-0.372 to-0.476 for IL-113 and -0.168 to-0.311 for CRP.Conclusion: Findings from the current study shows that cognitive deficits are reflective of elevated proin-flammatory biomarkers (IL-6, IL-113, TNF-alpha and CRP) levels. The results obtained indicate relatedness between inflammation and cognitive decline in patients with schizophrenia. Understanding the underlying pathways between them could have a significant impact on the disease progression and quality of life in schizophrenia patients.

Automated summary

This study examines the association between Interleukin-6 (IL-6), IL-113, Tumor Necrosis Factor-alpha, and CRP with cognitive dysfunction in schizophrenia patients. The meta-analyses results show a significant inverse relationship between cognitive performance and systemic levels of these inflammatory markers. Understanding the connection between inflammation and cognitive decline in schizophrenia patients can have a significant impact on disease progression and quality of life.