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

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-1β, Tumor Necrosis Factor-α and CRP with cognitive dysfunction.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-1β, TNF-α and CRP.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-1β, TNF-α and CRP plasma levels in patients with schizophrenia. The meta-analyses results showed a significant decline in the cognitive performances 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-α -0.372 to -0.476 for IL-1β and - 0.168 to -0.311 for CRP.Findings from the current study shows that cognitive deficits are reflective of elevated proinflammatory biomarkers (IL-6, IL-1β, TNF-α 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.