title: Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain.
abstract: Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158 allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.
authors.affiliation: Psychiatric Neuroscience Group, Department of Neurological and Psychiatric Sciences, University of Bari, 70124 Bari, Italy. bertolia@psichiat.uniba.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
authors.forename: Valeria
authors.initials: V
authors.lastname: Latorre
authors.forename: Valeria
authors.initials: V
authors.lastname: Rubino
authors.forename: Antonio
authors.initials: A
authors.lastname: Rampino
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sinibaldi
authors.forename: Grazia
authors.initials: G
authors.lastname: Caforio
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Scarabino
authors.forename: Marcello
authors.initials: M
authors.lastname: Nardini
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002540:Cerebral Cortex / Q000502:physiology*; D004298:Dopamine / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D007802:Language; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology*; D012016:Reference Values
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase; D004298:Dopamine