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Psychoneuroendocrinology. 2015 Dec;62:18-26. doi: 10.1016/j.psyneuen.2015.07.002. Epub 2015 Jul 8.

Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis.

Author information

Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address:
Memory Research Laboratory, Brain Institute (ICe), Federal University of Rio Grande do Norte (UFRN), Natal, RN, Brazil.
Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada; Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ON, Canada.
Laboratory of Neurophysiology and Neuroimaging, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe Universität, Frankfurt/Main, Germany.
Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil; Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St, Ste 670, Philadelphia, PA 19104, USA.
Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia; Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia; Department of Psychiatry, Florey Institute of Neuroscience and Mental Health, Orygen, The National Centre of Excellence in Youth Mental Health and Orygen Youth Health Research Centre, University of Melbourne, Parkville, VIC, Australia.



The neurotrophic hypothesis of major depressive disorder (MDD) postulates that the pathology of this illness incorporates a down-regulation of neurotrophin signaling. Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophic mediator regarding the neurobiology of MDD. Nevertheless, emerging evidence has implicated the multi-competent angiogenic and neurogenic molecule - vascular endothelial growth factor (VEGF) - in hippocampal neurogenesis and depression pathophysiology.


To compare peripheral levels of VEGF between individuals with MDD and healthy controls.


We performed a systematic review and meta-analysis of original studies measuring peripheral levels of VEGF in participants with MDD compared to healthy controls. We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases for studies published in any language through December 16th, 2014.


Fourteen studies met eligibility criteria (N=1633). VEGF levels were significantly elevated in individuals with MDD when compared to healthy controls (Hedges's g=0.343; 95% CI: 0.146-0.540; P<0.01). Funnel plot inspection and the Egger's test did not provide evidence of publication bias. A significant degree of heterogeneity was observed (Q=38.355, df=13, P<0.001; I(2)=66.1%), which was explored through meta-regression and subgroup analyses. Overall methodological quality, sample for assay (plasma versus serum), as well as the matching of MDD and control samples for age and gender emerged as significant sources of heterogeneity.


Taken together, extant data indicate that VEGF shows promise as a biomarker for MDD, and supports that this mediator may be involved in neuroplasticity mechanisms underlying the pathophysiology of MDD.


Biomarker; Depression; Major depressive disorder; Meta-analysis; Neuronal plasticity; Vascular endothelial growth factor

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