Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain.
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.
Bertolino
Alessandro
A
Psychiatric Neuroscience Group, Department of Neurological and Psychiatric Sciences, University of Bari, 70124 Bari, Italy. bertolia@psichiat.uniba.it
Blasi
Giuseppe
G
Latorre
Valeria
V
Rubino
Valeria
V
Rampino
Antonio
A
Sinibaldi
Lorenzo
L
Caforio
Grazia
G
Petruzzella
Vittoria
V
Pizzuti
Antonio
A
Scarabino
Tommaso
T
Nardini
Marcello
M
Weinberger
Daniel R
DR
Dallapiccola
Bruno
B
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
D050483:Dopamine Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase; D004298:Dopamine