Experimental Evidence for Differential Susceptibility: Dopamine D4 Receptor Polymorphism (drd4 Vntr) Moderates Intervention Effects on Toddlers' Externalizing Behavior in a Randomized Controlled Trial Differential Susceptibility and Genetic Vulnerability

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. Externalizing behaviors in preschoolers predict a variety of problems in later childhood and even in toddlers externalizing behavior shows considerable stability (Alink et al., 2006). The development of externalizing problems has been associated with environmental influences, in particular inadequate par-Little is known about the interplay between genetic and environmental factors in shaping externalizing behaviors. Some descriptive longitudinal studies on insensitive or harsh parenting found evidence for the importance of genetic vulnerabilities in predicting externalizing behavior in early childhood (Bakermans-Kranenburg & Van IJzendoorn, 2006) or antisocial behavior in adulthood (Caspi et al., 2002). In the current experimental intervention study we examined whether toddlers' genetic differences may explain differential effectiveness of an intervention aimed at decreasing externalizing behavior through improving parental discipline and interaction skills. To our knowledge the current study is the first experimental test of (measured) gene by (observed) environment interaction in child development. Almost 40 years ago, Thomas, Chess, and Birch (1968) had already noted that infant characteristics may interact with parent-ing to produce poorer (or better) child outcomes. 2007) recently emphasized the evolutionary rationale for varying susceptibility to environmental influences in siblings. In a continually changing and essentially unpredictable environment the transmission of one's genes will be facilitated by a diversification of investments, that is, offspring with a differential susceptibility to various environments. Similarly, Boyce and Ellis (2005a, 2005b) posited an evolutionary– developmental theory of varying Koot …