Circulating inflammatory cytokines influencing schizophrenia: a Mendelian randomization study

Introduction: Schizophrenia (SCZ) is a severe psychiatric disorder whose pathophysiology remains elusive. Recent investigations have underscored the significance of systemic inflammation, particularly the impact of circulating inflammatory proteins, in SCZ.

Methods: This study explores the potential causal association between certain inflammatory proteins and SCZ. Bidirectional Mendelian randomization (MR) analyses were conducted utilizing data from expansive genome-wide association studies (GWAS). Data regarding circulating inflammatory proteins were sourced from the GWAS Catalog database, encompassing 91 inflammatory cytokines. SCZ-related data were derived from the Finngen database, incorporating 47,696 cases and 359,290 controls. Analytical methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode were employed to evaluate the association between inflammatory cytokines and SCZ. Sensitivity analyses were also performed to affirm the robustness of the results.

Results: Following FDR adjustment, significant associations were observed between levels of inflammatory cytokines, including Fibroblast Growth Factor 5 (OR = 1.140, 95%CI = 1.045, 1.243, p = 0.003, FDR=0.015), C-C Motif Chemokine 4 (OR = 0.888, 95%CI = 0.816, 0.967, p = 0.006, FDR = 0.015), C-X-C Motif Chemokine 1 (OR = 0.833, 95%CI = 0.721, 0.962, p = 0.013, FDR = 0.064), and C-X-C Motif Chemokine 5 (OR = 0.870, 95%CI = 0.778, 0.973, p = 0.015, FDR = 0.074), and the risk of SCZ.

Conclusion: Our results from MR analysis suggest a potential causal link between circulating inflammatory cytokines and SCZ, thereby enriching our understanding of the interactions between inflammation and SCZ. Furthermore, these insights provide a valuable foundation for devising therapeutic strategies targeting inflammation.