title: Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Forde
authors.affiliation: Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: lr344@cam.ac.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ronan
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: 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.
authors.forename: Cathy
authors.initials: C
authors.lastname: Scanlon
authors.affiliation: 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.
authors.forename: Simon
authors.initials: S
authors.lastname: Neary
authors.affiliation: 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.
authors.forename: Laurena
authors.initials: L
authors.lastname: Holleran
authors.affiliation: Image Sciences Institute University Medical Center Utrecht, The Netherlands. Electronic address: Alexander@isi.uu.nl.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK. Electronic address: Rt337@cam.ac.uk.
authors.forename: Roger
authors.initials: R
authors.lastname: Tait
authors.affiliation: Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: cr439@cam.ac.uk.
authors.forename: Catarina
authors.initials: C
authors.lastname: Rua
authors.affiliation: 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.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Fletcher
authors.affiliation: iMinds Vision Lab, University of Antwerp, Belgium. Electronic address: Ben.jeurissen@ua.ac.be.
authors.forename: Ben
authors.initials: B
authors.lastname: Jeurissen
authors.affiliation: GlaxoSmithKline, Clinical Unit Cambridge, UK. Electronic address: Chrismdodds@googlemail.com.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Dodds
authors.affiliation: GlaxoSmithKline, Clinical Unit Cambridge, UK. Electronic address: sam.r.miller@gsk.com.
authors.forename: Sam R
authors.initials: SR
authors.lastname: Miller
authors.affiliation: 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.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: 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.
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.affiliation: 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.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: 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.
authors.forename: Dara M
authors.initials: DM
authors.lastname: Cannon
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001921:Brain / Q000033:anatomy & histology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D056324:Diffusion Tensor Imaging; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; Diffusion; Intrinsic curvature; MRI; Structural; Val66met