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Biological and genetic factors, as well as contextual influences, contribute to the etiology of externalizing behaviors in children and adolescents. The current project used a longitudinal design to examine how individual vulnerability for externalizing behavior is influenced by the interplay among biological/genetic and environmental factors, and how this occurs across development. We investigated the influence of dopamine receptor D4 genotype (DRD4), child temperament, and household chaos on children's externalizing behaviors using a sample of twins/triplets tested at the ages of 4 and 5 years (n = 229), including a subset of these who were tested again in middle childhood (ages 7–13 years; n = 174). Multilevel linear regression modeling demonstrated that the DRD4‐7repeat genotype, 4‐year‐old negative affectivity, and household chaos at the age of 4 years were related to 5‐year‐old externalizing behaviors. Stability in externalizing behaviors from the age of 5 years to middle childhood was demonstrated. A significant interaction between DRD4 and household chaos showed that children with no 7‐repeat DRD4 alleles had significantly higher levels of externalizing in homes with extremely low levels of parent‐reported chaos, suggesting a "goodness‐of‐fit" pattern of gene–environment interaction. These findings suggest that risk for childhood externalizing behaviors is likely multifaceted and differs across developmental periods. [ABSTRACT FROM AUTHOR]

Introduction The long allele of the DRD4 gene can confer different behavioral and emotional phenotypes depending upon environmental exposure, although the physiological changes underlying these phenotypes are not fully known. We sought to extend this work by assessing the interaction of the DRD4 gene and exposure to perinatal adversity (indexed by extremely low birth weight [ELBW]) on resting respiratory sinus arrhythmia (RSA), a neurophysiological measure of emotion regulation, in adulthood. Methods We examined the interaction between the DRD4 gene and perinatal adversity on RSA at age 30-35 in a longitudinal cohort of ELBW survivors ( n = 49) and NBW controls ( n = 63). Buccal DNA samples were genotyped for short and long carriers of the exon III DRD4 VNTR gene. Resting RSA was assessed by electrocardiogram. Results We report an interaction between birth weight status and DRD4 gene ( F = 9.42, p = 0.003) in predicting RSA, such that DRD4 long carriers had the highest and lowest resting RSA depending on whether they were born NBW or ELBW, respectively. DRD4 short carriers were less sensitive to birth weight. Additionally, reduced RSA was correlated with a history of major depressive disorder, suggesting it was a reliable index of emotion dysregulation. Discussion These results suggest that the perinatal environment influences autonomic nervous system functioning in individuals with genotypes that confer additional sensitivity. Whether the long-term autonomic outcomes of this environmental sensitivity are beneficial or detrimental appears to depend on the quality of the early life environment, and may influence the development of emotion regulatory and psychiatric problems in adulthood. [ABSTRACT FROM AUTHOR]

We determined whether the combination of fetal genotype (dopamine D4 receptor; DRD4) and mothers' anxiety during pregnancy is associated with fetal behavior. Two hundred and six pregnant women underwent an ultrasound exam. Fetal movement measures (Movement Frequency, Total Activity, Movement Duration, and Longest Quiet Time) were derived from off-line coding. A moderating role of the DRD4-III polymorphism was found: Results indicate that higher levels of antenatal maternal anxiety symptoms were associated with more frequent fetal movements among fetuses carrying a 7R allele, but not among fetuses carrying shorter alleles. Total Activity did not show full moderation by DRD4, though the measure was correlated with maternal anxiety among fetuses in the Anxious Group with a 7R allele; not among fetuses without both factors. The findings provide the first evidence of a GXE interaction in association with fetal behavior. Results also demonstrate that some individuals are inherently more susceptible to uterine environmental influences than are others. [ABSTRACT FROM AUTHOR]

ABSTRACT This study is the first to investigate the longitudinal effects of gene-environment interplay between DRD4 genotype and maternal sensitivity on child externalizing behavior. Multiple measures of maternal sensitivity (14, 36, and 48 months) and externalizing behavior (18 months, 36 months, and 5 years) were assessed in a large cohort study ( N = 548). Early maternal insensitivity (14 months) was associated with early externalizing behavior (18 months) in a for better and for worse manner, but only in children with at least one DRD4 7-repeat, consistent with a differential susceptibility model. Later insensitivity (48 months) predicted externalizing behavior at age 5 independent of DRD4 genotype. A structural equation model including all measures across time supported the differential susceptibility model: The overall effect of early maternal sensitivity on later externalizing behavior was significant only for children with a DRD4 7-repeat allele. The results highlight the importance of studying gene-environment interactions across development. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 57: 35-49, 2015. [ABSTRACT FROM AUTHOR]

We determined whether the combination of the 48-bp variable number tandem repeat polymorphism of the dopamine (DRD4) gene and infants' (fussy-difficult) temperament predicted parenting sensitivity. The sample was comprised of 147 mothers and their 6-month olds. Sensitive parenting was assessed by coding filmed interactions between mothers and infants. Infant temperament was assessed by parents' reports on a standard questionnaire. Moderated regressions models, with maternal education and infants' interactive behavior as controls, were used to test our hypotheses. Results showed no main effects of either temperament or DRD4, though the maternal DRD4 × infant temperament interaction was significant. Probes indicated that parents with a DRD4 7-repeat allele behaved more sensitively to fussier infants and less sensitively to less fussy infants compared to parents without the 7-repeat allele. Among those parents, sensitivity did not vary with infant temperament. This pattern of results indicates that mothers are differentially susceptible to infant fussiness, dependent on the presence of the 7-repeat DRD4 allele. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:149–157, 2010 [ABSTRACT FROM AUTHOR]

This study examined effects from a specific dopamine receptor gene (DRD4), environmental influences from parents and peers, and the interaction between them, on aggressive and prosocial behaviors of preschoolers. Children were classified as DRD4-L (n = 27) if they had at least one DRD4 allele with six to eight repeats and as DRD4-S (n = 35) if not. Parent–child interactions were coded when children were 3–4 years old. Peer interaction data and parent questionnaires were collected at age 5. DRD4-L children shared less with each other and parents were less sensitive during parent–twin triadic interactions. Also, genotype interacted with peer aggression to affect children's aggression during a peer play interaction at age 5, and genotype interacted with prior parental sensitivity to affect later externalizing problems. Thus, children having a certain genetic disposition may be more sensitive to certain environmental stimuli and therefore more likely to exhibit aggressive behaviors under more stressful circumstances. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 451–464, 2009 [ABSTRACT FROM AUTHOR]

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. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 48: 406–409, 2006. [ABSTRACT FROM AUTHOR]