title: The BDNF Val66Met polymorphism is associated with structural neuroanatomical differences in young children.
abstract: The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with individual differences in brain structure and function, and cognition. Research on BDNF's influence on brain and cognition has largely been limited to adults, and little is known about the association of this gene, and specifically the Val66Met polymorphism, with developing brain structure and emerging cognitive functions in children. We performed a targeted genetic association analysis on cortical thickness, surface area, and subcortical volume in 78 children (ages 6-10) who were Val homozygotes (homozygous Val/Val carriers) or Met carriers (Val/Met, Met/Met) for the Val66Met locus using Atlas-based brain segmentation. We observed greater cortical thickness for Val homozygotes in regions supporting declarative memory systems (anterior temporal pole/entorhinal cortex), consistent with adult findings. Met carriers had greater surface area in the prefrontal and parietal cortices and greater cortical thickness in lateral occipital/parietal cortex in contrast to prior adult findings that may relate to performance on cognitive tasks supported by these regions in Met carriers. Finally, we found larger right hippocampal volume in Met carriers, although inconsistent with adult findings (generally reports larger volumes for Val homozygotes), is consistent with a recent finding in children. Gene expression levels vary across different brain regions and across development and our findings highlight the need to consider this developmental change in explorations of BDNF-brain relationships. The impact of the BDNF Val66Met polymorphism on the structure of the developing brain therefore reflects regionally-specific developmental changes in BDNF expression and cortical maturation trajectories.
authors.affiliation: University of Delaware, Newark, DE, USA; Haskins Laboratories, New Haven, CT, USA. Electronic address: jasinska@udel.edu.
authors.forename: Kaja K
authors.initials: KK
authors.lastname: Jasińska
authors.affiliation: Haskins Laboratories, New Haven, CT, USA; University of Connecticut, Storrs, CT, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Molfese
authors.affiliation: Haskins Laboratories, New Haven, CT, USA; University of Houston, Houston, TX, USA; Baylor College of Medicine, Houston, TX, USA; Moscow State University, Moscow, Russian Federation; Saint-Petersburg State University, Saint-Petersburg, Russian Federation.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Kornilov
authors.affiliation: Haskins Laboratories, New Haven, CT, USA; Yale University, New Haven, CT, USA.
authors.forename: W Einar
authors.initials: WE
authors.lastname: Mencl
authors.affiliation: Haskins Laboratories, New Haven, CT, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Frost
authors.affiliation: Yale University, New Haven, CT, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Lee
authors.affiliation: Haskins Laboratories, New Haven, CT, USA; University of Connecticut, Storrs, CT, USA; Yale University, New Haven, CT, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Pugh
authors.affiliation: Haskins Laboratories, New Haven, CT, USA; Yale University, New Haven, CT, USA; University of Houston, Houston, TX, USA; Baylor College of Medicine, Houston, TX, USA; Moscow State University, Moscow, Russian Federation; Saint-Petersburg State University, Saint-Petersburg, Russian Federation; Moscow State University for Psychology and Education, Moscow, Russian Federation.
authors.forename: Elena L
authors.initials: EL
authors.lastname: Grigorenko
authors.affiliation: Haskins Laboratories, New Haven, CT, USA; University of Connecticut, Storrs, CT, USA; Yale University, New Haven, CT, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Landi
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006624:Hippocampus / Q000000981:diagnostic imaging*; D006801:Humans; D007360:Intelligence; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; Cortical thickness; Development; Gray matter volume; Neurogenetics; Surface area; rs6265; sMRI neuroimaging