Brief Report| Volume 64, ISSUE 10, P901-903, November 15, 2008

Influence of Vascular Endothelial Growth Factor Variation on Human Hippocampus Morphology


      Morphological abnormalities in hippocampus have been implicated in neuropsychiatric disorders, including depression, schizophrenia, and dementia. Vascular endothelial growth factor (VEGF) has been demonstrated to have neurogenic effects in the hippocampus in rats. However, influence of VEGF variation on hippocampus morphology in humans has yet to be shown. Here, an integrated genetic and neuroimaging approach was used to investigate whether VEGF variation influences hippocampus morphology in humans.


      High-resolution magnetic resonance imaging and voxel-based morphometry were used to identify the influence of genetic variation of VEGFA [rs833068 (SNP-1), rs833070 (SNP-2), rs2146323 (SNP-3) and rs3025020 (SNP-4)] on brain morphology in 47 healthy individuals.


      Variation in VEGFA SNP-2 and SNP-3 showed significant effects on hippocampus concentration.


      The findings suggest that effects of VEGF in hippocampus found in rats extend to humans; further understanding of effects of VEGFA variation might have important implications in identifying individuals more vulnerable to hippocampus pathology as well as those neuropsychiatric populations most likely to benefit from VEGF-mediated interventions.

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        • Warner-Schmidt J.L.
        • Duman R.S.
        VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants.
        Proc Natl Acad Sci U S A. 2007; 104: 4647-4652
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        Structured Clinical Interview for DSM-IV Axis I & II Disorders (Version 2.0).
        Biometrics Research, New York State Psychiatric Institute, New York1995
        • Tang Y.
        • Wang F.
        • Xie G.
        • Liu J.
        • Li L.
        • Su L.
        • et al.
        Reduced ventral anterior cingulate and amygdala volumes in medication-naive females with major depressive disorder: A voxel-based morphometric magnetic resonance imaging study.
        Psychiatry Res. 2007; 156: 83-86
        • Good C.D.
        • Johnsrude I.S.
        • Ashburner J.
        • Henson R.N.
        • Friston K.J.
        • Frackowiak R.S.
        A voxel-based morphometric study of ageing in 465 normal adult human brains.
        Neuroimage. 2001; 14: 21-36
        • Barrett J.C.
        • Fry B.
        • Maller J.
        • Daly M.J.
        Haploview: Analysis and visualization of LD and haplotype maps.
        Bioinformatics. 2005; 21: 263-265
        • Jin K.
        • Zhu Y.
        • Sun Y.
        • Mao X.O.
        • Xie L.
        • Greenberg D.A.
        Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo.
        Proc Natl Acad Sci U S A. 2002; 99: 11946-11950
        • Matsuzaki H.
        • Tamatani M.
        • Yamaguchi A.
        • Namikawa K.
        • Kiyama H.
        • Vitek M.P.
        • et al.
        Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity: Signal transduction cascades.
        Faseb J. 2001; 15: 1218-1220
        • Cao L.
        • Jiao X.
        • Zuzga D.S.
        • Liu Y.
        • Fong D.M.
        • Young D.
        • et al.
        VEGF links hippocampal activity with neurogenesis, learning and memory.
        Nat Genet. 2004; 36: 827-835
        • Fabel K.
        • Fabel K.
        • Tam B.
        • Kaufer D.
        • Baiker A.
        • Simmons N.
        • et al.
        VEGF is necessary for exercise-induced adult hippocampal neurogenesis.
        Eur J Neurosci. 2003; 18: 2803-2812
        • Tischer E.
        • Mitchell R.
        • Hartman T.
        • Silva M.
        • Gospodarowicz D.
        • Fiddes J.C.
        • et al.
        The human gene for vascular endothelial growth factor.
        J Biol Chem. 1991; 266: 11947-11954
        • Ashburner J.
        • Friston K.J.
        Voxel-based morphometry—the methods.
        Neuroimage. 2000; 11: 805-821
        • Jin K.L.
        • Mao X.O.
        • Greenberg D.A.
        Vascular endothelial growth factor: Direct neuroprotective effect in in vitro ischemia.
        Proc Natl Acad Sci U S A. 2000; 97: 10242-10247
        • Oosthuyse B.
        • Moons L.
        • Storkebaum E.
        • Beck H.
        • Nuyens D.
        • Brusselmans K.
        • et al.
        Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.
        Nat Genet. 2001; 28: 131-138
        • McCloskey D.P.
        • Croll S.D.
        • Scharfman H.E.
        Depression of synaptic transmission by vascular endothelial growth factor in adult rat hippocampus and evidence for increased efficacy after chronic seizures.
        J Neurosci. 2005; 25: 8889-8897

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      • Erratum
        Biological PsychiatryVol. 65Issue 1
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          An error in the key for Figure 1 has been discovered in the article “Influence of Vascular Endothelial Growth Factor Variation on Human Hippocampus Morphology” by Blumberg et al., which appeared in Biological Psychiatry, Volume 64, Number 10 (Biol Psychiatry 2008; 64:901–903). In the key for Figure 1, the labels for CC and T carriers in the left figure and CC and A carriers in the right figure are switched. Therefore, the T carriers in the left graph and the A carriers in the right graph are actually represented by the black-colored diamonds, and the white-colored diamonds represent the CC.
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