Vascular Endothelial Growth Factor and Brain-Derived Neurotrophic Factor in Quetiapine Treated First-Episode Psychosis

Brendan P Murphy,Tina-Marie Proffitt,Patrick D Mcgorry,Melissa Kerr,Terence Y Pang,Connie Markulev,Mirabel Mcconchie,Anthony J Hannan,Colin O’Donnell,Gregor E Berger

doi:10.1155/2014/719395

Abstract

Objective. It has been suggested that atypical antipsychotics confer their effects via brain-derived neurotrophic factor (BDNF). We investigated the effect of quetiapine on serum levels of BDNF and vascular endothelial growth factor (VEGF) in drug-naive first-episode psychosis subjects. Methods. Fifteen patients drawn from a larger study received quetiapine treatment for twelve weeks. Baseline levels of serum BDNF and VEGF were compared to age- and sex-matched healthy controls and to levels following treatment. Linear regression analyses were performed to determine the relationship of BDNF and VEGF levels with outcome measures at baseline and week 12. Results. The mean serum BDNF level was significantly higher at week 12 compared to baseline and correlated with reductions in Brief Psychiatric Rating Scale (BPRS) and general psychopathology scores. Changes in serum VEGF levels also correlated significantly with a reduction in BPRS scores, a significant improvement in PANNS positive symptoms scores, and displayed a positive relationship with changes in BDNF levels. Conclusions. Our findings suggest that BDNF and VEGF are potential biomarkers for gauging improvement of psychotic symptoms. This suggests a novel neurotrophic-based mechanism of the drug effects of quetiapine on psychosis. This is the first report of VEGF perturbation in psychosis.

Highlights

The precise molecular mechanisms mediating the actions of antipsychotic drugs remain poorly understood [1]
One-way ANOVA found a significant difference in the mean serum brain-derived neurotrophic factor (BDNF) levels between the groups (F(2,51) = 7.797; P = 0.0011; Figure 1(a)), and post hoc testing revealed that this was significantly higher in the Week 12 patient group compared to baseline (Wk12 versus Wk0: P = 0.012) but not compared to the control group (P = 0.0256)
While there was no correlation between the absolute serum concentration and outcome measures at baseline or week 12, we found that the change in serum BDNF levels was positively correlated with specific reductions in Brief Psychiatric Rating Scale (BPRS) and PANSS general psychopathology scores

Summary

Introduction

The precise molecular mechanisms mediating the actions of antipsychotic drugs remain poorly understood [1]. Evidence from rodent studies suggests that this protective effect is mediated by an upregulation of brain-derived neurotrophic factor (BDNF) in the brain [3,4,5]. A review of animal studies concluded that, with the exception of risperidone, atypical antipsychotics might increase BDNF expression while conventional antipsychotics might decrease expression [6]. Risperidone’s inability to alter expression of BDNF or to even increase it at higher doses (Favelli) suggests differential effects of atypical antipsychotics on BDNF expression. Olanzapine and risperidone significantly increase D2 binding in the medial prefrontal cortex and hippocampus, whilst quetiapine does not. Olanzapine and risperidone produce significant up-regulation of D4 receptors in the hippocampus, caudate-putamen, and nucleus accumbens, whilst quetiapine does not [7]. Quetiapine’s inability to adjust dopamine receptors suggests that nondopaminergic

Methods

Results

Conclusion