Key Publications

• Bakermans-Kranenburg, M.J. & Van IJzendoorn, M.H. (2008). Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social Cognitive and Affective Neuroscience, 3, 128-134.
  Abstract
  Both oxytocin and serotonin modulate affiliative responses to partners and offspring. Animal studies suggest a crucial role of oxytocin in mammalian parturition and lactation but also in parenting and social interactions with offspring. The serotonergic system may also be important through its influence on mood and the release of oxytocin. We examined the role of serotonin transporter (5-HTT) and oxytocin receptor (OXTR) genes in explaining differences in sensitive parenting in a community sample of 159 Caucasian, middle-class mothers with their 2-year-old toddlers at risk for externalizing behavior problems, taking into account maternal educational level, maternal depression and the quality of the marital relationship. Independent genetic effects of 5-HTTLPR SCL6A4 and OXTR rs53576 on observed maternal sensitivity were found. Controlling for differences in maternal education, depression and marital discord, parents with the possibly less efficient variants of the serotonergic (5-HTT ss) and oxytonergic (AA/AG) system genes showed lower levels of sensitive responsiveness to their toddlers. Two-way and three-way interactions with marital discord or depression were not significant. This first study on the role of both OXTR and 5-HTT genes in human parenting points to molecular genetic differences that may be implicated in the production of oxytocin explaining differences in sensitive parenting. 
• Bakermans-Kranenburg, M.J., Van IJzendoorn, M.H.,  Mesman, J., Alink, L.R.A.,  &  Juffer, F. (2008). Effects of an attachment-based intervention on daily cortisol moderated by DRD4: A randomized control trial on 1-3-year-olds screened for externalizing behavior. Development & Psychopathology, 20, 805-820.
  Abstract
  The effect of the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) on daily cortisol production was tested in a randomized controlled trial with 130 families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior. Six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline were conducted with individual families at their homes. Children in the intervention group showed lower cortisol levels, with a moderating role of the dopamine receptor D4 (DRD4) VNTR exon III polymorphism. The VIPP-SD program proved to be effective in decreasing daily cortisol production in children with the DRD4 7-repeat allele, but not in children without the DRD4 7-repeat allele. Our findings indicate that children are differentially susceptible to intervention effects dependent on the presence of the 7-repeat DRD4 allele.
• Bakermans-Kranenburg, M.J., Van IJzendoorn, M.H., Pijlman, F.T.A., Mesman, J., &  Juffer, F. (2008). Differential susceptibility to intervention: Dopamine D4 Receptor Polymorphism (DRD4 VNTR) moderates effects on toddlers’ externalizing behavior in a randomized control trial. Developmental Psychology, 44, 293-300.
  Abstract 
  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.
• Bakermans-Kranenburg, M.J. & Van IJzendoorn, M.H. (2007) Genetic vulnerability or differential susceptibility in child development: The case of attachment. Journal of Child Psychology and Psychiatry, 48, 1160-1173. 
  Abstract
  Gene-environment interactions interpreted in terms of differential susceptibility may play a large part in the explanation of individual differences in human development. Reviewing studies on the behavioral and molecular genetics of attachment, we present evidence for interactions between genetic and environmental factors explaining individual differences in attachment security and disorganization. In particular, the DRD4 7-repeat polymorphism seems associated with an increased risk for disorganized attachment, but only when combined with environmental risk. Gene-environment (G x E) interactions may be interpreted as genetic vulnerability or differential susceptibility. We found support for the differential susceptibility hypothesis predicting not only more negative outcomes for susceptible children in unfavorable environments, but also positive outcomes for susceptible children in favorable environments.
• Van IJzendoorn, M.H., & Bakermans-Kranenburg, M.J. (2006). DRD4 7-repeat polymorphism moderates the association between maternal unresolved loss or trauma and infant disorganization. Attachment & Human Development, 8, 291-307. 
  Abstract 
  Previous studies have related attachment disorganization in children to either dopamine D4 receptor polymorphisms or maternal unresolved loss or trauma and frightening or anomalous parenting. In this study it was examined whether the interaction between genetic (DRD4 7-repeat and -521 C/T) and environmental risk factors (maternal unresolved loss/trauma and maternal frightening behavior) was associated with infant disorganization. A moderating role of the DRD4 gene was found. Maternal unresolved loss or trauma was associated with infant disorganization, but only in the presence of the DRD4 7-repeat polymorphism. The increase in risk for disorganization in children with the 7-repeat allele exposed to maternal unresolved loss/trauma compared to children without these combined risks was 18.8 fold. Similar moderating effects were not found for maternal frightening behavior. Our findings indicate that children are differentially susceptible to unresolved loss or trauma dependent on the presence of the 7-repeat DRD4 allele.
• Bakermans-Kranenburg, M.J. & Van IJzendoorn, M.H. (2006). Gene-environment interaction of the Dopamine D4 receptor (DRD4) and observed maternal insensitivity predicting externalizing behavior in preschoolers. Developmental Psychobiology, 48, 406-409.
  Abstract
  Previous studies have related aggression and other externalizing problems in children to either dopamine D4 receptor polymorphisms or harsh and insensitive parenting. In this study it was determined whether the combination of the DRD4 7-repeat polymorphism and maternal insensitivity predicted significantly more externalizing behavior in preschoolers. The results pointed to a gene–environment interaction effect: maternal insensitivity was associated with externalizing (oppositional, aggressive) behaviors, but only in the presence of the DRD4 7-repeat polymorphism. The increase in externalizing behaviors in children with the 7-repeat allele exposed to insensitive care compared to children without these combined risks was sixfold. The data indicate that children are differentially susceptible to insensitive parenting dependent on the presence of the 7-repeat DRD4 allele.