Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study

INTRODUCTION: Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. METHODS: A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. RESULTS: Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = −0.212, p = 0.010) and in the subgroup with higher positive scores (r = −0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. DISCUSSION: TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.