Cognitive dysfunction in schizophrenia: association with peripheral blood inflammatory signatures.

Abstract

Background: Schizophrenia (SCZ) is a complex, chronic neuropsychiatric disorder involving genetic, neurotransmitter, and immune system interactions. The immune-inflammatory hypothesis has emerged as a key research focus, with evidence suggesting that aberrant peripheral inflammatory factors may cross the blood-brain barrier, contributing to neurodegeneration and cognitive impairment. However, most studies have focused on single or a few inflammatory factors, with heterogeneous results, and their clinical utility as biomarkers remains unclear. This study aims to identify differentially expressed inflammatory factors in the peripheral blood of SCZ patients undergoing olanzapine treatment, evaluate their diagnostic efficacy using multidimensional statistical modeling, and investigate correlations with positive/negative symptoms and cognitive function, providing new insights into immune-inflammatory mechanisms.

Methods: We recruited 40 SCZ patients on monotherapy with olanzapine as the study group and 40 individuals without a psychiatric history as the healthy control group, collecting their blood samples and basic demographic data. The levels of inflammatory factors were measured using a flow cytometric immunoassay with fluorescently encoded microspheres. Symptom severity was assessed using the PANSS, and cognitive function was evaluated using the MCCB.

Results: Compared to healthy controls, SCZ showed significantly elevated Eotaxin and MCP1 levels and cognitive deficits across all MCCB cognitive domains. LASSO regression and Boruta algorithm identified Eotaxin and MCP1 as key predictors. Although these biomarkers were not associated with PANSS scores (p > 0.05), Eotaxin showed negative correlations with all MCCB subdomains (p < 0.05), while MCP1 correlated negatively with processing speed (p = 0.042) and attention/vigilance (p = 0.017). The final model demonstrated good discrimination (AUC = 0.838, 95% CI: 0.750-0.825) and calibration (p = 0.8958).

Conclusion: Eotaxin may clarify cognitive impairments in SCZ patients, while MCP1 mainly focuses on the aspects of attention/vigilance as evaluated by the MCCB. Eotaxin and MCP1 are potential biomarkers for SCZ.