Self-esteem in remitted patients with mood disorders is not associated with the dopamine receptor D4 and the serotonin transporter genes

AbstractData drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.

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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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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

Development and Psychopathology ◽

10.1017/s0954579407000569 ◽

2007 ◽

Vol 19 (4) ◽

pp. 1105-1116 ◽

Cited By ~ 30

Author(s):

Louis A. Schmidt ◽

Nathan A. Fox ◽

Dean H. Hamer

Keyword(s):

Behavior Problems ◽

Dopamine Receptor ◽

Serotonin Transporter ◽

Child Behavior Checklist ◽

Externalizing Behaviors ◽

Typically Developing ◽

Short Allele ◽

Internalizing And Externalizing Behaviors ◽

Internalizing And Externalizing ◽

Dopamine Receptor D4

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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Dopamine receptor D4 gene is associated with delusional symptomatology in mood disorders

Psychiatry Research ◽

10.1016/s0165-1781(98)00056-0 ◽

1998 ◽

Vol 80 (2) ◽

pp. 129-136 ◽

Cited By ~ 27

Author(s):

Alessandro Serretti ◽

Fabio Macciardi ◽

Cristina Cusin ◽

Enrico Lattuada ◽

Roberta Lilli ◽

...

Keyword(s):

Mood Disorders ◽

Dopamine Receptor ◽

Dopamine Receptor D4

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Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months

Development and Psychopathology ◽

10.1017/s0954579416000560 ◽

2016 ◽

Vol 29 (3) ◽

pp. 901-917 ◽

Cited By ~ 17

Author(s):

Cathryn Gordon Green ◽

Vanessa Babineau ◽

Alexia Jolicoeur-Martineau ◽

Andrée-Anne Bouvette-Turcot ◽

Klaus Minde ◽

...

Keyword(s):

Maternal Depression ◽

Dopamine Receptor ◽

Serotonin Transporter ◽

Interaction Model ◽

Negative Emotionality ◽

Prenatal Depression ◽

Genetic Profile ◽

Polymorphic Region ◽

Region Gene ◽

Dopamine Receptor D4

AbstractPrenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months.

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Interaction between serotonin transporter promoter and dopamine receptor D4 polymorphisms on decision making

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2009.07.009 ◽

2009 ◽

Vol 33 (7) ◽

pp. 1217-1222 ◽

Cited By ~ 16

Author(s):

Ra Yeon Ha ◽

Kee Namkoong ◽

Jee In Kang ◽

Yang Tae Kim ◽

Se Joo Kim

Keyword(s):

Decision Making ◽

Dopamine Receptor ◽

Serotonin Transporter ◽

Dopamine Receptor D4

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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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