Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism.

TitleStructural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism.
Publication TypeJournal Article
Year of Publication2014
AuthorsForde, N. J., L. Ronan, J. Suckling, C. Scanlon, S. Neary, L. Holleran, A. Leemans, R. Tait, C. Rua, P. C. Fletcher, B. Jeurissen, C. M. Dodds, S. R. Miller, E. T. Bullmore, C. McDonald, P. J. Nathan, and D. M. Cannon
Date Published2014 Apr 15
KeywordsAdolescent, Adult, Alleles, Brain, Brain-Derived Neurotrophic Factor, diffusion tensor imaging, Female, Genotype, Heterozygote, Homozygote, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Polymorphism, Single Nucleotide, Young Adult

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.

Alternate JournalNeuroimage
PubMed ID24384148