Background: 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
Objective: To compare peripheral levels of VEGF between individuals with
MDD and healthy controls.
Methods: 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.
Results: 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% Cl: 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
Conclusions: 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. (C) 2015 Elsevier Ltd. All rights reserved.
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