title: Catechol-O-methyltransferase polymorphism modulates cognitive control in children with chromosome 22q11.2 deletion syndrome.
abstract: Dopamine plays a critical role in regulating neural activity in prefrontal cortex (PFC) and modulates cognition via a hypothesized inverse U function. We investigated PFC function in children with chromosome 22q11.2 deletion syndrome (22q11.2DS) in which one copy of catechol-O-methyltransferase (COMT) is deleted, thereby shifting them toward the lower end of dopamine turnover on the nonlinear function. A common polymorphism with valine to methionine substitution alters COMT activity that results in higher enzyme activity in the valine variant. Twenty-seven children with 22q11.2DS between 7 and 14 years old, and 21 age-matched typically developing children, performed a modified version of the Attention Network Test. Children with a single valine allele showed a reduction in response times when trials with incongruent flankers were repeated, whereas those who were hemizygous for the methionine allele did not show the same context-based response facilitation. Our results support that a single gene, COMT, could modulate PFC-dependent cognition.
authors.affiliation: University of California, Davis, California, USA. ytakarae@ucdavis.edu
authors.forename: Yukari
authors.initials: Y
authors.lastname: Takarae
authors.forename: Linda
authors.initials: L
authors.lastname: Schmidt
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001288:Attention / Q000502:physiology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004062:DiGeorge Syndrome / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D011930:Reaction Time / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine