COMT genotype and resting brain perfusion in children

Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase ( COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in...

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Veröffentlicht in:	NeuroImage (Orlando, Fla.) Jg. 48; H. 1; S. 217 - 222
Hauptverfasser:	Thomason, Moriah E., Waugh, Christian E., Glover, Gary H., Gotlib, Ian H.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Elsevier Inc 15.10.2009 Elsevier Limited
Schlagworte:	Adolescent Analysis of Variance Behavior Brain - blood supply Brain - physiology Catechol O-Methyltransferase - genetics Cerebrovascular Circulation - genetics Cerebrovascular Circulation - physiology Child Enzymes Female Genotype Genotype & phenotype Haplotypes Humans Magnetic Resonance Imaging Male Perfusion Imaging Polymorphism, Genetic Regional Blood Flow Rest Sequence Analysis, DNA Studies
ISSN:	1053-8119, 1095-9572, 1095-9572
Online-Zugang:	Volltext
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Abstract	Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase ( COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development.
AbstractList	Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development.Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development. Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development. Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase ( COMT) gene. In vivo studies of this polymorphism in the human brain have typically measured patterns of neural activation during dopamine-mediated tasks in adults. This study is the first to investigate the effects of COMT on brain physiology during rest and in children. We used flow-sensitive arterial spin-labeling (ASL) magnetic resonance imaging to examine brain blood flow (CBF) in 42 children. Compared with val-allele carriers, met-allele homozygotes exhibited greater CBF in mesolimbic, mesocortical, and nigrostriatal dopamine (DA) pathways. Higher CBF in DA-rich brain structures reflects COMT-related baseline differences that (1) underlie the selective behavioral advantages associated with each genotype; (2) affect interpretations of previously reported genotype differences in BOLD signal changes; and (3) serve as a foundation for future studies on the effects of COMT on brain development.
Author	Waugh, Christian E. Gotlib, Ian H. Glover, Gary H. Thomason, Moriah E.
AuthorAffiliation	2 Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 1 Department of Psychology, Stanford University, Stanford, CA 94305
AuthorAffiliation_xml	– name: 1 Department of Psychology, Stanford University, Stanford, CA 94305 – name: 2 Department of Radiology, Stanford University School of Medicine, Stanford, California 94305
Author_xml	– sequence: 1 givenname: Moriah E. surname: Thomason fullname: Thomason, Moriah E. email: moriah@stanford.edu organization: Department of Psychology, Stanford University, Stanford, CA 94305, USA – sequence: 2 givenname: Christian E. surname: Waugh fullname: Waugh, Christian E. organization: Department of Psychology, Stanford University, Stanford, CA 94305, USA – sequence: 3 givenname: Gary H. surname: Glover fullname: Glover, Gary H. organization: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA – sequence: 4 givenname: Ian H. surname: Gotlib fullname: Gotlib, Ian H. organization: Department of Psychology, Stanford University, Stanford, CA 94305, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/19500679$$D View this record in MEDLINE/PubMed
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Copyright	2009 Elsevier Inc. Copyright Elsevier Limited Oct 15, 2009 2009 Elsevier Inc. All rights reserved. 2009
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Snippet	Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase ( COMT) gene. In... Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the val158met locus of the catechol-O-methyltransferase (COMT) gene. In... Levels of extra-synaptic dopamine in the brain vary as a function of polymorphisms at the Val158Met locus of the catechol-O-methyltransferase (COMT) gene. In...
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SubjectTerms	Adolescent Analysis of Variance Behavior Brain - blood supply Brain - physiology Catechol O-Methyltransferase - genetics Cerebrovascular Circulation - genetics Cerebrovascular Circulation - physiology Child Enzymes Female Genotype Genotype & phenotype Haplotypes Humans Magnetic Resonance Imaging Male Perfusion Imaging Polymorphism, Genetic Regional Blood Flow Rest Sequence Analysis, DNA Studies
Title	COMT genotype and resting brain perfusion in children
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