title: Effects of the BDNF Val66Met Polymorphism on Gray Matter Volume in Typically Developing Children and Adolescents.
abstract: The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) is associated with psychiatric disorders and regional gray matter volume (rGMV) in adults. However, the relationship between BDNF and rGMV in children has not been clarified. In this 3-year cross-sectional/longitudinal (2 time points) study, we investigated the effects of BDNF genotypes on rGMV in 185 healthy Japanese children aged 5.7-18.4 using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analyses. We found that the volume of the right cuneus in Met homozygotes (Met/Met) was greater than in Val homozygotes (Val/Val) in both exams, and the left insula and left ventromedial prefrontal cortex volumes were greater in Val homozygotes versus Met homozygotes in Exam l. In addition, Met homozygous subjects exhibited higher processing speed in intelligence indices than Val homozygotes and Val/Met heterozygotes at both time points. Longitudinal analysis showed that the left temporoparietal junction volume of Val/Met heterozygotes increased more substantially over the 3-year study period than in Val homozygotes, and age-related changes were observed for the Val/Met genotype. Our findings suggest that the presence of 2 Met alleles may have a positive effect on rGMV at the developmental stages analyzed in this study.
authors.affiliation: Division of Developmental Cognitive Neuroscience.
authors.forename: Teruo
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Nuclear Medicine and Radiology, Division of Medical Neuroimaging Analysis, Institute Development, Aging and Cancer.
authors.forename: Kento
authors.initials: K
authors.lastname: Fukui
authors.affiliation: Division of Developmental Cognitive Neuroscience.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Division of Developmental Cognitive Neuroscience.
authors.forename: Susumu
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Disaster Psychiatry, International Research Institute of Disaster Science.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Disaster Psychiatry, International Research Institute of Disaster Science.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Division of Developmental Cognitive Neuroscience Department of Nuclear Medicine and Radiology, Division of Medical Neuroimaging Analysis, Institute Development, Aging and Cancer Department of Community Medical Supports, Tohoku Medical Megabank Organization, Tohoku University, 980-8575 Sendai, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Taki
authors.affiliation: Division of Developmental Cognitive Neuroscience.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kawashima
mesh_terms: D000293:Adolescent; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000033:anatomy & histology* / Q000254:growth & development*; D006801:Humans; D007360:Intelligence / Q000502:physiology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: MRI; cross-sectional study; development; longitudinal study; voxel-based morphometry
references.citation: Dev Psychol. 2011 Sep;47(5):1431-9
references.pmid: 21688896
references.citation: Pathophysiology. 2011 Feb;18(1):53-60
references.pmid: 20478698
references.citation: Hum Brain Mapp. 2015 Feb;36(2):549-65
references.pmid: 25271132
references.citation: Genes Brain Behav. 2008 Jun;7(4):411-7
references.pmid: 17973920
references.citation: Isr J Psychiatry Relat Sci. 2012;49(2):137-42
references.pmid: 22801293
references.citation: J Physiol. 2008 Dec 1;586(23):5717-25
references.pmid: 18845611
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2008 Oct 1;32(7):1652-5
references.pmid: 18621091
references.citation: Biol Psychiatry. 2004 Sep 1;56(5):376-8
references.pmid: 15336520
references.citation: Brain Res Bull. 2011 Nov 25;86(5-6):287-97
references.pmid: 21924328
references.citation: Mol Psychiatry. 2006 May;11(5):505-13
references.pmid: 16446742
references.citation: Neuropsychology. 2009 Jan;23(1):105-16
references.pmid: 19210038
references.citation: Exp Neurol. 2009 Jan;215(1):178-90
references.pmid: 19014937
references.citation: Wiley Interdiscip Rev Cogn Sci. 2015 Mar-Apr;6(2):97-108
references.pmid: 26263066
references.citation: Cell. 2003 Jan 24;112(2):257-69
references.pmid: 12553913
references.citation: Cereb Cortex. 2010 Mar;20(3):534-48
references.pmid: 19520764
references.citation: Neuropsychopharmacology. 2010 Apr;35(5):1083-9
references.pmid: 20042999
references.citation: Nat Rev Neurosci. 2013 Jan;14(1):7-23
references.pmid: 23254191
references.citation: Acta Neurobiol Exp (Wars). 2010;70(4):454-67
references.pmid: 21196952
references.citation: Psychiatry Investig. 2013 Jun;10(2):173-9
references.pmid: 23798966
references.citation: Ann Rheum Dis. 2006 Oct;65(10):1330-5
references.pmid: 16606648
references.citation: Mol Psychiatry. 2010 Aug;15(8):810-5
references.pmid: 19255578
references.citation: Neuroscience. 2010 Mar 10;166(1):178-84
references.pmid: 20034542
references.citation: Psychol Med. 2009 Nov;39(11):1831-9
references.pmid: 19335934
references.citation: J Neurosci. 2004 Nov 10;24(45):10099-102
references.pmid: 15537879
references.citation: Cereb Cortex. 2010 Feb;20(2):411-24
references.pmid: 19502476
references.citation: J Gerontol A Biol Sci Med Sci. 2014 Aug;69(8):996-1003
references.pmid: 24170673
references.citation: Neuropsychobiology. 2004;49(1):13-6
references.pmid: 14730195
references.citation: J Neurosci. 2011 Aug 24;31(34):12139-48
references.pmid: 21865456
references.citation: Cereb Cortex. 2012 Jan;22(1):1-12
references.pmid: 21613470
references.citation: Nat Rev Neurosci. 2008 Dec;9(12):947-57
references.pmid: 19002191
references.citation: Cereb Cortex. 2014 May;24(5):1230-46
references.pmid: 23283688
references.citation: Science. 2001 Nov 30;294(5548):1945-8
references.pmid: 11729324
references.citation: Neuroscience. 2009 Nov 24;164(1):108-20
references.pmid: 19358879
references.citation: Mol Psychiatry. 2012 Oct;17(10):1026-30
references.pmid: 22614288
references.citation: Dev Cogn Neurosci. 2015 Aug;14:1-7
references.pmid: 26046425
references.citation: Age (Dordr). 2012 Dec;34(6):1529-41
references.pmid: 21898033
references.citation: Neurosci Biobehav Rev. 2015 Aug;55:107-18
references.pmid: 25956254
references.citation: Biol Psychiatry. 2006 May 1;59(9):812-5
references.pmid: 16442082
references.citation: Neurosci Lett. 2006 Apr 10-17;397(1-2):25-9
references.pmid: 16388901
references.citation: J Neurosci. 2003 Jul 30;23(17):6690-4
references.pmid: 12890761
references.citation: J Magn Reson Imaging. 2013 Jun;37(6):1468-75
references.pmid: 23172789
references.citation: Neuromolecular Med. 2014 Mar;16(1):127-36
references.pmid: 24366608
references.citation: Science. 2006 Oct 6;314(5796):140-3
references.pmid: 17023662
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2012 Sep;159B(6):731-40
references.pmid: 22815222
references.citation: Neuroimage. 2011 Jan 15;54(2):992-1000
references.pmid: 20849959
references.citation: Dev Neurosci. 2015;37(2):153-60
references.pmid: 25721327
references.citation: World J Biol Psychiatry. 2011 Mar;12(2):110-8
references.pmid: 20726825
references.citation: J Am Acad Child Adolesc Psychiatry. 2013 Feb;52(2):184-95
references.pmid: 23357445
references.citation: Nat Rev Neurosci. 2001 Jan;2(1):24-32
references.pmid: 11253356
references.citation: Mol Psychiatry. 2015 Aug;20(8):916-30
references.pmid: 25824305