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&...

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Published in:The Journal of neuroscience 2006-04, Vol.26 (15), p.3918-3922
Main Authors: Bertolino, Alessandro, Blasi, Giuseppe, Latorre, Valeria, Rubino, Valeria, Rampino, Antonio, Sinibaldi, Lorenzo, Caforio, Grazia, Petruzzella, Vittoria, Pizzuti, Antonio, Scarabino, Tommaso, Nardini, Marcello, Weinberger, Daniel R, Dallapiccola, Bruno
Format: Article
Language:English
Subjects:
Adult
Brain Mapping
Brief Communications
Catechol O-Methyltransferase - genetics
Cerebral Cortex - physiology
Dopamine - genetics
Dopamine Plasma Membrane Transport Proteins - genetics
Female
Gene Expression Regulation
Genetic Variation
Humans
Language
Magnetic Resonance Imaging
Male
Memory - physiology
Reaction Time - physiology
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.4975-05.2006