Associations between plasma BDNF, VEGF, and EGF and cognition in drug-naïve schizophrenia with and without sleep disturbances

Cognitive impairment is core symptom in schizophrenia (SCZ), and sleep disturbances (SD) are common and linked to worse cognition. The roles of plasma brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) in drug-naïve SCZ, particularly across SD strata, remain unclear.

We enrolled 138 drug-naïve patients with SCZ at Tianjin Anding Hospital and stratified them by Pittsburgh Sleep Quality Index (PSQI) into the sleep disturbance group (SCZ-SD) (n = 81) and the non-sleep disturbance group (SCZ-NSD) (n = 57). Cognition was assessed with the MATRICS Consensus Cognitive Battery (MCCB). Plasma BDNF, VEGF, and EGF were quantified by enzyme-linked immunosorbent assay (ELISA). Group comparisons, partial correlations, receiver operating characteristic (ROC) analyses, and sensitivity analyses were conducted.

SCZ-SD patients showed more severe cognitive impairment than SCZ-NSD, particularly in Verbal Learning, Visual Learning, and composite scores (P < 0.05). In SCZ-SD, BDNF was positively correlated with multiple cognitive domains (FDR-adjusted P < 0.05) and showed modest discriminative ability for cognitive impairment with an area under the curve (AUC) of 0.648. In SCZ-NSD, EGF showed a nominal, exploratory association with use of sleep medication (uncorrected P < 0.05), and the combined plasma-marker model demonstrated fair discrimination of cognitive impairment (AUC = 0.694).

SCZ-SD patients showed more severe cognitive impairment, and higher BDNF was robustly associated with better cognitive performance. In contrast, SCZ-NSD patients showed associations between EGF and sleep-related measures. These findings suggest distinct biological pathways linking sleep and cognition in SCZ with and without SD, though their current discriminative accuracy suggests an adjunctive rather than standalone diagnostic role.