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Neuroimage. 2014 Apr 15;90:280-9. doi: 10.1016/j.neuroimage.2013.12.050. Epub 2013 Dec 31.

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

Author information

1
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Electronic address: j.natalieforde@gmail.com.
2
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: lr344@cam.ac.uk.
3
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK; Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK. Electronic address: js369@cam.ac.uk.
4
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Electronic address: cathy.scanlon@nuigalway.ie.
5
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Electronic address: s.neary2@nuigalway.ie.
6
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Electronic address: l.holleran1@nuigalway.ie.
7
Image Sciences Institute University Medical Center Utrecht, The Netherlands. Electronic address: Alexander@isi.uu.nl.
8
Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK. Electronic address: Rt337@cam.ac.uk.
9
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: cr439@cam.ac.uk.
10
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK; Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK. Electronic address: pcf22@cam.ac.uk.
11
iMinds Vision Lab, University of Antwerp, Belgium. Electronic address: Ben.jeurissen@ua.ac.be.
12
GlaxoSmithKline, Clinical Unit Cambridge, UK. Electronic address: Chrismdodds@googlemail.com.
13
GlaxoSmithKline, Clinical Unit Cambridge, UK. Electronic address: sam.r.miller@gsk.com.
14
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK; GlaxoSmithKline, Clinical Unit Cambridge, UK; Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK. Electronic address: etb23@cam.ac.uk.
15
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Electronic address: colm.mcdonald@nuigalway.ie.
16
Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK; GlaxoSmithKline, Clinical Unit Cambridge, UK; School of Psychology and Psychiatry, Monash University, Australia. Electronic address: pn254@cam.ac.uk.
17
Clinical Neuroimaging Laboratory, School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland. Electronic address: dara.cannon@nuigalway.ie.

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.

KEYWORDS:

BDNF; Diffusion; Intrinsic curvature; MRI; Structural; Val66met

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