Evidence for a gene–gene interaction in predicting children's behavior problems: Association of serotonin transporter short and dopamine receptor D4 long genotypes with internalizing and externalizing behaviors in typically developing 7-year-olds

AbstractRecent work on the molecular genetics of complex traits in typical and atypical human development has focused primarilyon associations of single genes with behavior. Disparate literature suggests that the presence of one or two copies of the short allele of the serotonin transporter (5-HTT) gene and the long allele (7-repeat allele) version of the dopamine receptor D4 (DRD4) gene predicts internalizing- and externalizing-related behaviors, respectively. Apparently for the first time in the extant literature, we report a gene–gene statistical interaction on behavior problems in a group of typically developing children at age 7. DNA was extracted from buccal cells collected from 108 children and genotyped for short and long alleles of the5-HTTgene and the short (2–5 repeats) versus long (6–8 repeats) allele of theDRD4gene. Mothers completed the Child Behavior Checklist. As predicted, children with one or two copies of the short allele of the5-HTTgeneandthe long allele version of theDRD4gene exhibited significantly more internalizing and externalizing behaviors at age 7 than children with other combinations of the5-HTTandDRD4short and long genotypes. As well, children with the5-HTTlongand DRD4long genotypes had the lowest reported scores on internalizing and externalizing behaviors at age 7, suggesting that the presence of the5-HTTlong genotype may serve as a protective factor against these behaviors in children with the longDRD4genotype. Implications of these findings for understanding cumulative biological risk and protective factors in childhood behavior problems and psychopathology are discussed.

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Advances on Parental Educational Styles Predictors of Internalizing and Externalizing Behaviors in Children

Universitas Psychologica ◽

10.11144/javeriana.upsy18-5.apes ◽

2019 ◽

Vol 18 (5) ◽

pp. 1-10

Author(s):

Jaime Humberto Moreno Méndez ◽

José Pedro Espada Sánchez ◽

Inmaculada Gómez Becerra

Keyword(s):

Public Schools ◽

Internalizing Problems ◽

Externalizing Problems ◽

Child Behavior Checklist ◽

Externalizing Behaviors ◽

Internalizing And Externalizing Problems ◽

Internalizing And Externalizing Behaviors ◽

Externalizing And Internalizing Problems ◽

Communication Difficulties ◽

Internalizing And Externalizing

The purposes of this study were to perform a psychometric analysis of the Parental Educational Styles Questionnaire and to evaluate its predictive validity on externalizing and internalizing problems in Colombian children. Participants were 680 parents (M= 37.34; SD= 9.2) of children aged between 8 and 12 years enrolled in public schools in Bogota, Colombia. The parental educational styles questionnaire and the child behavior checklist -parents format- were applied to the participants. The resulting model presents the best indicators of favorable fit according to confirmatory factorial analyses. These values show an internal consistence of the instrument. The results indicate that dysfunctional reaction to disobedience, communication difficulties and conflicts predicted internalizing and externalizing problems.

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Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence

Development and Psychopathology ◽

10.1017/s0954579407000594 ◽

2007 ◽

Vol 19 (4) ◽

pp. 1147-1160 ◽

Cited By ~ 49

Author(s):

Maria Nobile ◽

Roberto Giorda ◽

Cecilia Marino ◽

Ombretta Carlet ◽

Valentina Pastore ◽

...

Keyword(s):

Socioeconomic Status ◽

Dopamine Receptor ◽

Serotonin Transporter ◽

Promoter Region ◽

Child Behavior Checklist ◽

Population Sample ◽

Aggressive Behaviors ◽

Rule Breaking ◽

The Impact ◽

Dopamine Receptor D4

AbstractThe impact of socioeconomic status (SES) and genetic polymorphisms on individual differences for externalized behaviors have often been investigated separately in studies of children and adults. In a general population sample of 607 Italian preadolescents, we examined the independent and joint effects of SES and the dopamine receptor D4 (DRD4) and serotonin transporter linked promoter region (5-HTTLPR) polymorphisms upon rule-breaking and aggressive behaviors measured with the Child Behavior CheckList/6–18. We found evidence, which was based on both one locus and two-loci genotype analyses, that low SES andDRD4long and5-HTTLPRlong alleles, both alone and in interaction, are associated with higher aggressive behavior scores. The effects were similar but more modest and limited to one locus genotype analyses for rule-breaking behavior. Consistent with studies that showed the effects of societal moderators on the heritability of externalized behaviors across different segments of the population, we suggest that diminished social constraints associated with low parental SES may act as enhancers of the genetic influence of specificDRD4and5-HTTLPRalleles over aggressive behaviors in preadolescence.

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Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments

Development and Psychopathology ◽

10.1017/s0954579414001369 ◽

2015 ◽

Vol 27 (1) ◽

pp. 151-162 ◽

Cited By ~ 76

Author(s):

Marinus H. van Ijzendoorn ◽

Marian J. Bakermans-Kranenburg

Keyword(s):

Confidence Interval ◽

Dopamine Receptor ◽

Serotonin Transporter ◽

Differential Susceptibility ◽

Environment Interaction ◽

Polymorphic Region ◽

Short Allele ◽

Repeat Allele ◽

Gene Environment ◽

Dopamine Receptor D4

AbstractThe most stringent test of differential susceptibility theory is provided by randomized control trials examining the moderating role of genetic markers of differential susceptibility in experimental manipulations of the environment (Gene × Experimental Environment interactions), being at least 10 times more powerful than correlational Gene × Environment interaction studies. We identified 22 experiments involving 3,257 participants with various developmental outcomes (e.g., externalizing problems, internalizing behaviors, and cognitive development). Effect sizes contrasting experimental versus control group were computed both for subjects with the polymorphism considered indicative of heightened susceptibility (e.g., the dopamine receptor D4 gene seven-repeat allele and the serotonin transporter polymorphic region short allele) and others expected to be low in susceptibility (e.g., the dopamine receptor D4 gene four-repeat allele and the serotonin transporter polymorphic region short allele). Clear-cut experimental support for genetic differential susceptibility emerged: the combined effect size of the interventions for the susceptible genotypes amounted to r = .33 (95% confidence interval = 0.23, 0.42; p < .01) versus a nonsignificant r = .08 (95% confidence interval = −0.02, 0.17; p = .12) for the hypothesized nonsusceptible genotypes. Macrotrials showed more evidence of genetic differential susceptibility than microtrials, and differential susceptibility was more clearly observed in trials with externalizing and cognitive outcomes than with internalizing problems. This meta-analysis shows proof of principle for genetic differential susceptibility and indicates that it is time to explore its mechanisms and limits. The concept of differential susceptibility alters the idea of constitutional “risk” factors (reactive temperament and risk genotypes), and points to intervention efficacy hidden in Gene × Environment interactions.

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