Sex differences in the relationship between the vascular endothelial growth factor and cognition in drug-naïve...

This study investigates the sex-specific relationship between plasma Vascular Endothelial Growth Factor (VEGF) levels and cognitive performance in drug-naïve schizophrenia (DNS) patients, focusing on longitudinal changes.

A total of 175 DNS patients and 80 healthy controls (HCs) completed the MATRICS Consensus Cognitive Battery (MCCB). VEGF levels were measured via ELISA, and DNS patients were assessed using the Positive and Negative Syndrome Scale (PANSS). Partial correlations and multiple linear regressions were used to evaluate the relationships between VEGF, cognition, and symptom severity, adjusting for demographic and clinical factors.

Female DNS patients showed greater cognitive impairments than female HCs (all P < 0.05), while male DNS patients had specific deficits in Attention/Vigilance (P = 0.027) and Working Memory (P = 0.002). Among females, baseline VEGF levels were inversely correlated with psychotic symptoms, including PANSS Positive symptom scores (r = -0.281) and PANSS total scores (r = -0.224). Additionally, baseline VEGF levels were positively associated with cognitive performance, including Processing Speed (r = 0.302), Neurocognition (r = 0.193), and the MCCB total score (r = 0.201). In males, baseline VEGF levels showed a trend toward predicting less severe negative symptoms at the 8-week (β = -0.42, P = 0.060), though not statistically significant.

VEGF may protect cognition in female DNS patients through neuroprotective or anti-inflammatory mechanisms. Higher VEGF levels in females were linked to better cognition and milder symptoms over time. These findings suggest VEGF as a potential sex-specific biomarker for schizophrenia, warranting further investigation.