Experimental evidence for differential susceptibility: dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers' externalizing behavior in a randomized controlled trial

Dev Psychol. 2008 Jan;44(1):293-300. doi: 10.1037/0012-1649.44.1.293.


In a randomized controlled trial we tested the role of genetic differences in explaining variability in intervention effects on child externalizing behavior. One hundred fifty-seven families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior participated in a study implementing Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), with six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline. A moderating role of the dopamine D4 receptor (DRD4) variable-number tandem repeat (VNTR) exon III polymorphism was found: VIPP-SD proved to be effective in decreasing externalizing behavior in children with the DRD4 7-repeat allele, a polymorphism that is associated with motivational and reward mechanisms and Attention Deficit Hyperactivity Disorder (ADHD) in children. VIPP-SD effects were largest in children with the DRD4 7-repeat allele whose parents showed the largest increase in the use of positive discipline. The findings of this first experimental test of (measured) gene by (observed) environment interaction in human development indicate that children may be differentially susceptible to intervention effects depending on genetic differences.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Case-Control Studies
  • Child Behavior Disorders / genetics*
  • Child Behavior Disorders / psychology
  • Child Behavior Disorders / therapy*
  • Child, Preschool
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Infant
  • Maternal Behavior / psychology*
  • Minisatellite Repeats / genetics*
  • Parent-Child Relations
  • Parenting / psychology
  • Polymorphism, Genetic / genetics*
  • Receptors, Dopamine D4 / genetics*
  • Social Environment
  • Surveys and Questionnaires
  • Treatment Outcome


  • Receptors, Dopamine D4