Preliminary communication Peripheral vascular endothelial growth factor level is associated with antidepressant treatment response: Results of a preliminary study Zsuzsa Halmai a , Peter Dome a,n , Judit Dobos b , Xenia Gonda a , Anna Szekely c , Maria Sasvari-Szekely d , Gabor Faludi a , Judit Lazary a a Department of Clinical and Theoretical Mental Health, Kutvolgyi Clinical Center, Semmelweis University, Faculty of Medicine, Budapest, Hungary b Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary c Institute of Psychology, E¨ otv¨ os Lora ´nd University, Budapest, Hungary d Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary article info Article history: Received 8 May 2012 Received in revised form 4 September 2012 Accepted 5 September 2012 Available online 28 September 2012 Keywords: Vascular endothelial growth factor Major depressive disorder Bipolar disorder Treatment response Treatment resistance abstract Background: Recent investigations have revealed multiple actions of vascular endothelial growth factor (VEGF) in the nervous system. The role of VEGF in the molecular background of mood disorders has also been proposed. In this study we were interested in investigating a possible association between VEGF levels and treatment response in patients with a current episode of major depression (MDE). Methods: 34 patients with MDE were enrolled in our study. Depressive symptoms were monitored by the Montgomery– ˚ Asberg Depression Rating Scale at baseline (V 1 ) and after a 4-week treatment period (V 2 ). Patients with less than a 50% improvement in MADRS total scores during this period were regarded as non-responders. Results: Plasma VEGF levels did not change during the treatment period in either the total sample or in the responder and non-responder subsamples. There was a strong trend for higher baseline VEGF levels in the non-responder group than in the responder group (p ¼0.055) and this difference—as a weak trend—was still detectable at the end of the treatment period (p ¼0.097). Regression analysis revealed that the baseline VEGF level was a significant predictor for the endpoint MADRS score (p ¼0.02). Limitations: Sample size was relatively small; sample consists of both patients with MDD and bipolar disorder. Conclusions: Our preliminary results raise the possibility that baseline levels of peripheral VEGF may predict treatment response in patients with mood disorders. Considering the limitations of our study, further investigations should resolve whether VEGF is a useful biomarker for treatment response in depression in clinical practice. & 2012 Elsevier B.V. All rights reserved. 1. Introduction Mood disorders with episodes of major depression (as part of unipolar major depression and bipolar disorder) are frequent illnesses with enormous personal and social burdens worldwide. The life-time prevalence of major depressive and of bipolar disorders (MDD and BD) are 5–17% and 0.3–7.2%, respectively (Rihmer and Angst, 2005). Unfortunately, a considerable proportion (approximately one-third) of patients do not achieve remission even with the sequential use of various antidepressants, so despite intensive development of anti- depressants, treatment-resistant depression is still a serious challenge for clinicians (Stahl, 2008). Consequently, there is an urgent need to find predictive markers of pharmacological non-response in mood disorders to avoid wasting time and money on ineffective treatment and—based on that knowledge—to begin therapy (instead of/or alongside antidepressants) with alternative treatment modalities (e.g. electroconvulsive therapy; Gazdag et al., 2011). The vascular endothelial growth factor (VEGF) was discovered based on its ability to enhance vascular permeability, and subse- quently determined to be involved in several processes of the cardiovascular system (e.g. angiogenesis; vasodilatation; cardiac development; Viikki et al., 2010; Nieves et al., 2009; Testa et al., 2008). Later, several investigations showed that VEGF and/or its receptors are expressed by different cellular elements of the central nervous system (i.e. neurons, glial cells, ependymal cells and neuronal progenitors). In addition, VEGF has pleiotropic effects in the CNS (e.g. it stimulates migration, survival and proliferation of neural cells, and also regulates synaptic transmission in the hippocampus; Ruiz de Almodovar et al., 2009; Calvo et al., 2011; Huang et al., 2010; Zacchigna et al., 2008; Warner-Schmidt and Duman, 2008; Nowacka and Obuchowicz, 2012). Converging evidence from animal studies also suggests that VEGF is involved in the etiopathogenesis of depression. Accordingly, Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/jad Journal of Affective Disorders 0165-0327/$ - see front matter & 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jad.2012.09.006 n Correspondence to: Labdarozsa u. 17, Budapest H-1029, Hungary. Tel.: þ36 30 619 86 20; fax: þ36 1 391 33 10. E-mail address: dome_peter@yahoo.co.uk (P. Dome). Journal of Affective Disorders 144 (2013) 269–273