title: Age-Dependent Effects of Catechol-O-Methyltransferase (COMT) Gene Val158Met Polymorphism on Language Function in Developing Children.
abstract: The genetic basis controlling language development remains elusive. Previous studies of the catechol-O-methyltransferase (COMT) Val158Met genotype and cognition have focused on prefrontally guided executive functions involving dopamine. However, COMT may further influence posterior cortical regions implicated in language perception. We investigated whether COMT influences language ability and cortical language processing involving the posterior language regions in 246 children aged 6-10 years. We assessed language ability using a language test and cortical responses recorded during language processing using a word repetition task and functional near-infrared spectroscopy. The COMT genotype had significant effects on language performance and processing. Importantly, Met carriers outperformed Val homozygotes in language ability during the early elementary school years (6-8 years), whereas Val homozygotes exhibited significant language development during the later elementary school years. Both genotype groups exhibited equal language performance at approximately 10 years of age. Val homozygotes exhibited significantly less cortical activation compared with Met carriers during word processing, particularly at older ages. These findings regarding dopamine transmission efficacy may be explained by a hypothetical inverted U-shaped curve. Our findings indicate that the effects of the COMT genotype on language ability and cortical language processing may change in a narrow age window of 6-10 years.
authors.affiliation: Department of Language Sciences, Graduate School of Humanities, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.|Research Institute of Science and Technology for Society (RISTEX), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 100-0004, Japan.|Research Center for Language, Brain and Genetics, Tokyo Metropolitan University, Hachioji, Tokyo 192-037, Japan.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sugiura
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.affiliation: Department of Language Sciences, Graduate School of Humanities, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.|Research Institute of Science and Technology for Society (RISTEX), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 100-0004, Japan.|Laboratory for Language Development, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsuba-Kurita
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.affiliation: Laboratory for Language Development, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Mazuka
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Language Sciences, Graduate School of Humanities, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.|Research Institute of Science and Technology for Society (RISTEX), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 100-0004, Japan.|Research Center for Language, Brain and Genetics, Tokyo Metropolitan University, Hachioji, Tokyo 192-037, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hagiwara
mesh_terms: D000375:Aging / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002657:Child Development; D056344:Executive Function; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007802:Language; D007805:Language Development Disorders / Q000235:genetics*; D007807:Language Tests; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: catechol-O-methyltransferase (COMT); catecholamine; children; default mode network (DMN); development; dopamine; functional near-infrared spectroscopy (fNIRS); genotype; language; preadolescence