Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain

Alessandro Bertolino, Giuseppe Blasi, Valeria Latorre, Valeria Rubino, Antonio Rampino, Lorenzo Sinibaldi, Grazia Caforio, Vittoria Petruzzella, Antonio Pizzuti, Tommaso Scarabino, Marcello Nardini, Daniel R. Weinberger, Bruno Dallapiccola

Research output: Contribution to journalArticlepeer-review

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 DAT10-repeat allele have the most focused response, whereas the COMT Val and the DAT9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.

Original languageEnglish
Pages (from-to)3918-3922
Number of pages5
JournalJournal of Neuroscience
Volume26
Issue number15
DOIs
Publication statusPublished - 2006

Keywords

  • Anterior cingulate
  • Catechol-O-methyltransferase
  • Dopamine
  • Dopamine transporter
  • Dorsolateral prefrontal cortex
  • Working memory

ASJC Scopus subject areas

  • Neuroscience(all)

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