| Summary: | Abstract Objective Previous research has indicated the brain-derived neurotrophic factor (BDNF) level is lower in schizophrenia and associated with cognitive impairment. Irisin-BDNF axis may strengthen learning and memory functions. This study examined associations between BDNF, peroxisome proliferator-activated receptor-gamma (PPAR gamma) and irisin with cognitive deficits in schizophrenia. Methods We enrolled 80 patients with schizophrenia and 80 healthy controls (HCs). The enzyme-linked immunosorbent assay (ELISA) method was used for biochemical analysis. The Stroop Test, Trail Making Test (TMT), and Verbal Fluency Test (VFT) were used for cognitive assessment. Statistical analyses included t-tests, correlations, and analysis of covariance (ANCOVA) controlling key confounders. Results In unadjusted analyses, patients had significantly lower BDNF and PPARγ levels than HCs (ps < 0.001). After controlling for covariates, the difference in BDNF was still significant (F = 11804.71, p < 0.001, partial η² = 0.989), but not for PPARγ (F = 1.32, p = 0.252, partial η² = 0.010). Irisin levels did not differ between groups. Patients performed worse on all cognitive tests. After adjustments, deficits in processing speed (TMT-A, F = 4.30, p = 0.040) and executive function (Stroop-3, F = 5.89, p = 0.016; Stroop-4, F = 6.54, p = 0.012) remained significant. Longer illness duration correlated with lower BDNF (r=-0.318, p < 0.01), while more severe negative symptoms correlated with lower irisin (r=-0.244, p < 0.05). No biomarkers-cognition correlations were found groups separately. Exploratory analyses in the combined sample suggested nominal associations, but these did not survive correction for multiple comparisons and controlling for diagnostic group status. Conclusion BDNF demonstrates the most robust association with schizophrenia and cognitive function. The association of PPARγ with schizophrenia is confounded by demographic and metabolic factors, and irisin showed a limited link only to negative symptoms. Clinical trial number Not applicable.
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