Elsevier

NeuroImage

Volume 90, 15 April 2014, Pages 280-289
NeuroImage

Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism

https://doi.org/10.1016/j.neuroimage.2013.12.050Get rights and content
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open access

Highlights

  • Novelty of a met-homozygous group

  • We apply various complimentary advanced neuroimaging techniques.

  • Global and local changes are associated with the val66met polymorphism.

  • Changes do not occur in a dose dependant manner.

Abstract

Background

The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure.

Methods

To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography.

Results

Morphological analysis revealed an “inverted-U” shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles.

Conclusion

In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression.

Abbreviations

BDNF
brain derived neurotrophic factor
val
valine
met
methionine
AD
Alzheimer's Disease
MDD
Major depressive disorder
NAA
n-acetyl-asparate
VBM
voxel-based morphometry
CSD
constrained spherical deconvolution
EPI
echo planar imaging
DW
diffusion weighted
FOD
fibre orientation distribution
ILF
inferior longitudinal fasciculus
CB
cingulum bundle
UF
uncinate fasciculus
FA
fractional anisotropy
GLM
general linear model
TBSS
tract-based spatial statistics
ANCOVA
analysis of co-variance
TFCE
threshold-free cluster enhancement
ICC
intraclass correlation
SD
standard deviation
SNP
single nucleotide polymorphism

Keywords

BDNF
Structural
Diffusion
MRI
Val66met
Intrinsic curvature

Cited by (0)

1

Joint first author.