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

  • Bertolino A
  • Blasi G
  • Latorre V
 et al. 
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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.

Author-supplied keywords

  • Adult
  • Brain Mapping
  • Catechol O-Methyltransferase
  • Catechol O-Methyltransferase: genetics
  • Cerebral Cortex
  • Cerebral Cortex: physiology
  • Dopamine
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Plasma Membrane Transport Proteins: genet
  • Dopamine: genetics
  • Female
  • Gene Expression Regulation
  • Genetic Variation
  • Humans
  • Language
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Memory: physiology
  • Reaction Time
  • Reaction Time: physiology
  • Reference Values

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  • Alessandro Bertolino

  • Giuseppe Blasi

  • Valeria Latorre

  • Valeria Rubino

  • Antonio Rampino

  • Lorenzo Sinibaldi

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