Dopamine receptor D4 gene variation predicts preschoolers' developing theory of mind

Dev Sci. 2012 Mar;15(2):272-80. doi: 10.1111/j.1467-7687.2011.01124.x. Epub 2011 Dec 3.


Individual differences in preschoolers' understanding that human action is caused by internal mental states, or representational theory of mind (RTM), are heritable, as are developmental disorders such as autism in which RTM is particularly impaired. We investigated whether polymorphisms of genes affecting dopamine (DA) utilization and metabolism constitute part of the molecular basis of this heritability. Seventy-three 42- to 54-month-olds were given a battery of RTM tasks along with other task batteries that measured executive functioning and representational understanding more generally. Polymorphisms of the dopamine D4 receptor gene (DRD4) were associated with RTM performance such that preschoolers with shorter alleles outperformed those with one or more longer alleles. However, polymorphisms of the catechol-O-methyl transferase gene (COMT) and the dopamine transporter gene (DAT1) genes were not associated with children's RTM performance. Further tests showed that the association between DRD4 allele length and RTM performance was not attributable to a common association with executive functioning or representational understanding more generally. We conclude that DRD4 receptors, likely via their effects on frontal lobe development and functioning, may represent a neuromaturational constraint governing the stereotypical and universal trajectory of RTM development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Catechol O-Methyltransferase / genetics
  • Child Development / physiology*
  • Child, Preschool
  • DNA Primers / genetics
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Executive Function / physiology
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Male
  • Neuropsychological Tests
  • Ontario
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Genetic / physiology
  • Receptors, Dopamine D4 / genetics*
  • Receptors, Dopamine D4 / physiology
  • Theory of Mind / physiology*


  • DNA Primers
  • DRD4 protein, human
  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human
  • Receptors, Dopamine D4
  • Catechol O-Methyltransferase