Vascular endothelial growth factor in patients with schizophrenia: A systematic review and meta-analysis

Background: Accumulating evidence indicates that schizophrenia might be accompanied by abnormal vascularization. Vascular endothelial growth factor (VEGF) is one of key molecules involved in the development of vessels with vasodilatory activities. Objectives: We aimed to perform a systematic review and meta-analysis of studies investigating serum or plasma levels of VEGF in patients with schizophrenia and first-episode psychosis (FEP). Methods: Electronic databases were searched from their inception until 18th Apr 2018. Meta-analysis was performed using random-effects models with Hedges' g as the effect size estimate. Quality assessment was performed using the Newcastle-Ottawa Scale. Results: We included 15 eligible studies, representing 982 patients and 791 healthy controls. Main analysis revealed no significant differences in VEGF levels between patients and controls (g = 0.10, 95% CI = -0.24-0.45, p = .553). Subgroup analysis demonstrated unaltered levels of VEGF in FEP patients (g = 0.03, 95% CI = -0.53-0.59, p = .911), including antipsychotic-naive individuals (g = 0.34, 95% CI = -0.07-0.74, p = .103). However, the levels of VEGF were significantly higher in medicated multiple-episode schizophrenia (MES) patients (g = 0.45, 95% CI = 0.03-0.87, p = .036) compared to controls. Heterogeneity across studies was significant in the majority of analyses, except for the analysis of antipsychotic-naive FEP patients. Tests of asymmetry were insignificant, indicating a lack of publication bias. Limitations: Main limitations of our meta-analysis include inability to address medication effects exhaustively and relatively low number of studies in subgroup analyses. Conclusions: Our results indicate elevated levels of VEGF in MES patients that are unaltered in FEP individuals. Longitudinal studies are required to disentangle whether elevated levels of VEGF in MES patients reflect illness progression, comorbid physical health impairments or appear due to medication effects.