PMID- 24384148 OWN - NLM STAT- MEDLINE DCOM- 20141104 LR - 20220311 IS - 1095-9572 (Electronic) IS - 1053-8119 (Linking) VI - 90 DP - 2014 Apr 15 TI - Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism. PG - 280-9 LID - S1053-8119(13)01270-6 [pii] LID - 10.1016/j.neuroimage.2013.12.050 [doi] AB - 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. CI - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Forde, Natalie J AU - Forde NJ AD - 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. FAU - Ronan, Lisa AU - Ronan L AD - Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: lr344@cam.ac.uk. FAU - Suckling, John AU - Suckling J AD - 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. FAU - Scanlon, Cathy AU - Scanlon C AD - 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. FAU - Neary, Simon AU - Neary S AD - 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. FAU - Holleran, Laurena AU - Holleran L AD - 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. FAU - Leemans, Alexander AU - Leemans A AD - Image Sciences Institute University Medical Center Utrecht, The Netherlands. Electronic address: Alexander@isi.uu.nl. FAU - Tait, Roger AU - Tait R AD - Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, UK. Electronic address: Rt337@cam.ac.uk. FAU - Rua, Catarina AU - Rua C AD - Brain mapping unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: cr439@cam.ac.uk. FAU - Fletcher, Paul C AU - Fletcher PC AD - 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. FAU - Jeurissen, Ben AU - Jeurissen B AD - iMinds Vision Lab, University of Antwerp, Belgium. Electronic address: Ben.jeurissen@ua.ac.be. FAU - Dodds, Chris M AU - Dodds CM AD - GlaxoSmithKline, Clinical Unit Cambridge, UK. Electronic address: Chrismdodds@googlemail.com. FAU - Miller, Sam R AU - Miller SR AD - GlaxoSmithKline, Clinical Unit Cambridge, UK. Electronic address: sam.r.miller@gsk.com. FAU - Bullmore, Edward T AU - Bullmore ET AD - 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. FAU - McDonald, Colm AU - McDonald C AD - 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. FAU - Nathan, Pradeep J AU - Nathan PJ AD - 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. FAU - Cannon, Dara M AU - Cannon DM AD - 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. LA - eng GR - 095692/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131231 PL - United States TA - Neuroimage JT - NeuroImage JID - 9215515 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Adolescent MH - Adult MH - Alleles MH - Brain/*anatomy & histology MH - Brain-Derived Neurotrophic Factor/*genetics MH - Diffusion Tensor Imaging MH - Female MH - Genotype MH - Heterozygote MH - Homozygote MH - Humans MH - Image Processing, Computer-Assisted MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Young Adult OTO - NOTNLM OT - BDNF OT - Diffusion OT - Intrinsic curvature OT - MRI OT - Structural OT - Val66met EDAT- 2014/01/05 06:00 MHDA- 2014/11/05 06:00 CRDT- 2014/01/04 06:00 PHST- 2013/08/09 00:00 [received] PHST- 2013/12/11 00:00 [revised] PHST- 2013/12/16 00:00 [accepted] PHST- 2014/01/04 06:00 [entrez] PHST- 2014/01/05 06:00 [pubmed] PHST- 2014/11/05 06:00 [medline] AID - S1053-8119(13)01270-6 [pii] AID - 10.1016/j.neuroimage.2013.12.050 [doi] PST - ppublish SO - Neuroimage. 2014 Apr 15;90:280-9. doi: 10.1016/j.neuroimage.2013.12.050. Epub 2013 Dec 31.