Dopamine Receptor Gene DRD4 7-Repeat Allele X Maternal Sensitivity Interaction on Child Externalizing Behavior Problems: Independent Replication of Effects at 18 Months

Anthony P King,Katherine L Rosenblum,Alexander B Taylor,Maria Muzik,Israel Liberzon,Lindsay Hamilton

doi:10.1371/journal.pone.0160473

Abstract

The DRD4 VNTR has been associated with child behavior problems in interaction with maternal insensitivity in European and American cohorts of preschoolers, with the 7-repeat (7R) allele associated with greater problems. We sought to replicate and expand these findings by examining effects on reports of child behavior problems at 18 months. A 63 family sample with data for observed maternal sensitivity ratings, DRD4 VNTR genotype, and maternal report of child behavior problems at 18-months was used in this preliminary analysis. Maternal sensitivity was measured at 6-months of age using laboratory observational measures (free-play and a teaching task). Maternal report of toddler behavior was obtained at 18-months via the standard Child Behavior Checklist, and infant genotype on the DRD4 VNTR was obtained using PCR. Infants carrying the DRD4 7R allele showed greater effects of maternal insensitivity than non-carriers for behavioral problems at 18-months. We replicated previous findings of association of infant DRD4 x maternal sensitivity interactions with child Externalizing problems in the European-ancestry sample (N = 42) in a median split of maternal sensitivity (p = .00011, eta2 = .329) and in regression analyses controlling for maternal age, maternal depression, and child gender in European ancestry (B = -3.4, SE 1.33, p = .01) and the total sample (B = -2.2, SE 1.02, p = .02). Exploratory analyses also found evidence of DRD4 x maternal sensitivity interaction with the CBCL ADHD scale. These findings replicate in an independent cohort DRD4 x maternal insensitivity interaction effect on child externalizing behavior problems at 18 months, further supporting the role of the DRD4 genotype in differential sensitivity to parenting.

Highlights

Life measures of behavioral problems have been associated with increased risk for problematic adjustment across a range of developmental domains
DRD4 genotype was unrelated to maternal age and depression, child sex, and maternal interactive sensitivity at 6-months postpartum in the overall sample, and among European-ancestry children (Table 1)
DRD4 genotype was related to maternal sensitivity in the sub-sample of children with reported African ancestry (N = 21, Table 1)

Summary

Introduction

Life measures of behavioral problems have been associated with increased risk for problematic adjustment across a range of developmental domains (see review [1]). A small number of studies have shown evidence that the DRD4 7-repeat allele moderates the effects of low levels of maternal sensitivity on early childhood externalizing behaviors. Bakermans-Kranenburg & van Ijzendoorn [22] found a DRD4 7-repeat x maternal sensitivity (measured at 10 months of age) interaction that predicted externalizing behaviors at 39 months in an initial cohort of Netherlands toddlers. This paper was designed as an attempt to independently replicate DRD4 7-repeat allele x maternal interactive sensitivity on early childhood externalizing behaviors, using comparable observational measures of maternal sensitivity and similar analytic strategy, but focusing on observed maternal behaviors at an earlier time-point than previous studies (i.e., at 6 months of child age) and predicting to child externalizing behaviors at 18 months. The current literature a focus on very early risk behaviors in mother and child, both of which are known to be foundational for problematic developmental pathways [1]

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