title: COMT genotype affects prefrontal white matter pathways in children and adolescents.
abstract: Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.
authors.affiliation: Department of Psychology, Stanford University, Jordan Hall, Bldg. 420, Stanford, CA 94305-2130, USA. moriah@stanford.edu
authors.forename: Moriah E
authors.initials: ME
authors.lastname: Thomason
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dougherty
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Colich
authors.forename: Lee M
authors.initials: LM
authors.lastname: Perry
authors.forename: Elena I
authors.initials: EI
authors.lastname: Rykhlevskaia
authors.forename: Hugo M
authors.initials: HM
authors.lastname: Louro
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Hallmayer
authors.forename: Christian E
authors.initials: CE
authors.lastname: Waugh
authors.forename: Roland
authors.initials: R
authors.lastname: Bammer
authors.forename: Gary H
authors.initials: GH
authors.lastname: Glover
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gotlib
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D056324:Diffusion Tensor Imaging; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000378:metabolism*
chemical_list: D002394:Catechol O-Methyltransferase; D004298:Dopamine