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 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.
Thomason
Moriah E
ME
Department of Psychology, Stanford University, Stanford, CA 94305-2130, USA. moriah@stanford.edu
Waugh
Christian E
CE
Glover
Gary H
GH
Gotlib
Ian H
IH
D000293:Adolescent; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics* / Q000502:physiology*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D055420:Perfusion Imaging; D011110:Polymorphism, Genetic; D012039:Regional Blood Flow; D012146:Rest; D017422:Sequence Analysis, DNA
D002394:Catechol O-Methyltransferase