7-Repeat Allele

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Stephen B Manuck - One of the best experts on this subject based on the ideXlab platform.

  • polymorphic variation in the dopamine d4 receptor predicts delay discounting as a function of childhood socioeconomic status evidence for differential susceptibility
    Social Cognitive and Affective Neuroscience, 2013
    Co-Authors: Maggie M Sweitzer, Indrani Halder, Janine D Flory, Anna E Craig, Peter J Gianaros, Robert E Ferrell, Stephen B Manuck
    Abstract:

    Inconsistent or null findings among studies associating behaviors on the externalizing spectrumaddictions, impulsivity, risk-taking, novelty -seeking traitswith presence of the 7-Repeat Allele of a common length polymorphism in the gene encoding the dopamine D4 receptor ( DRD4) may stem from individualsvariable exposures to prominent environmental moderators (geneenvironment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-Repeat Allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-Repeat Allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participantsearly life circumstances, accords with a recently proposed developmental model of geneenvironment interaction (�differential susceptibility�) that posits genetically modulated sensitivity to both adverse and salubrious environm en- tal influences.

  • Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility
    Social Cognitive and Affective Neuroscience, 2012
    Co-Authors: Maggie M Sweitzer, Indrani Halder, Janine D Flory, Anna E Craig, Peter J Gianaros, Robert E Ferrell, Stephen B Manuck
    Abstract:

    Inconsistent or null findings among studies associating behaviors on the externalizing spectrumaddictions, impulsivity, risk-taking, novelty -seeking traitswith presence of the 7-Repeat Allele of a common length polymorphism in the gene encoding the dopamine D4 receptor ( DRD4) may stem from individualsvariable exposures to prominent environmental moderators (geneenvironment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-Repeat Allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-Repeat Allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participantsearly life circumstances, accords with a recently proposed developmental model of geneenvironment interaction (�differential susceptibility�) that posits genetically modulated sensitivity to both adverse and salubrious environm en- tal influences.

Maggie M Sweitzer - One of the best experts on this subject based on the ideXlab platform.

  • polymorphic variation in the dopamine d4 receptor predicts delay discounting as a function of childhood socioeconomic status evidence for differential susceptibility
    Social Cognitive and Affective Neuroscience, 2013
    Co-Authors: Maggie M Sweitzer, Indrani Halder, Janine D Flory, Anna E Craig, Peter J Gianaros, Robert E Ferrell, Stephen B Manuck
    Abstract:

    Inconsistent or null findings among studies associating behaviors on the externalizing spectrumaddictions, impulsivity, risk-taking, novelty -seeking traitswith presence of the 7-Repeat Allele of a common length polymorphism in the gene encoding the dopamine D4 receptor ( DRD4) may stem from individualsvariable exposures to prominent environmental moderators (geneenvironment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-Repeat Allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-Repeat Allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participantsearly life circumstances, accords with a recently proposed developmental model of geneenvironment interaction (�differential susceptibility�) that posits genetically modulated sensitivity to both adverse and salubrious environm en- tal influences.

  • Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility
    Social Cognitive and Affective Neuroscience, 2012
    Co-Authors: Maggie M Sweitzer, Indrani Halder, Janine D Flory, Anna E Craig, Peter J Gianaros, Robert E Ferrell, Stephen B Manuck
    Abstract:

    Inconsistent or null findings among studies associating behaviors on the externalizing spectrumaddictions, impulsivity, risk-taking, novelty -seeking traitswith presence of the 7-Repeat Allele of a common length polymorphism in the gene encoding the dopamine D4 receptor ( DRD4) may stem from individualsvariable exposures to prominent environmental moderators (geneenvironment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-Repeat Allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-Repeat Allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participantsearly life circumstances, accords with a recently proposed developmental model of geneenvironment interaction (�differential susceptibility�) that posits genetically modulated sensitivity to both adverse and salubrious environm en- tal influences.

Joseph Biederman - One of the best experts on this subject based on the ideXlab platform.

  • meta analysis of the association between the 7 repeat Allele of the dopamine d 4 receptor gene and attention deficit hyperactivity disorder
    American Journal of Psychiatry, 2001
    Co-Authors: Alysa E Doyle, Eric Mick, Joseph Biederman
    Abstract:

    OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-Repeat Allele of the dopamine D4 receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain. METHOD: Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. RESULTS: For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias. CONCLUSIONS: Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nea...

  • meta analysis of the association between the 7 repeat Allele of the dopamine d 4 receptor gene and attention deficit hyperactivity disorder
    American Journal of Psychiatry, 2001
    Co-Authors: Alysa E Doyle, Eric Mick, Joseph Biederman
    Abstract:

    OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-Repeat Allele of the dopamine D(4) receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain. METHOD: Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias. RESULTS: For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias. CONCLUSIONS: Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nearby gene) accounts for this association.

Barbara Franke - One of the best experts on this subject based on the ideXlab platform.

  • The dopamine receptor D4 7-Repeat Allele influences neurocognitive functioning, but this effect is moderated by age and ADHD status: An exploratory study
    The World Journal of Biological Psychiatry, 2011
    Co-Authors: Marieke E Altink, Barbara Franke, Cathelijne J M Buschgens, Nanda Rommelse, Ellen A Fliers, Dorine Slaats-willemse, Alejandro Arias Vasquez, Joseph A. Sergeant, Jaap Oosterlaan
    Abstract:

    AbstractObjectives. Evidence suggests the involvement of the dopamine D4 receptor gene (DRD4) in the pathogenesis of ADHD, but the exact mechanism is not well understood. Earlier reports on the effects of DRD4 polymorphisms on neurocognitive and neuroimaging measures are inconsistent. This study investigated the functional consequences of the 7-Repeat Allele of DRD4 on neurocognitive endophenotypes of ADHD in the Dutch subsample of the International Multicenter ADHD Genetics study. Methods. Participants were 350 children (5–11.5 years) and adolescents (11.6–19 years) with ADHD and their 195 non-affected siblings. An overall measure of neuropsychological functioning was derived by principal component analysis from five neurocognitive and five motor tasks. The effects of DRD4 and age were examined using Linear Mixed Model analyses. Results. The analyses were stratified for affected and non-affected participants after finding a significant three-way interaction between ADHD status, age and the 7-Repeat allel...

  • the dopamine receptor d4 7 repeat Allele and prenatal smoking in adhd affected children and their unaffected siblings no gene environment interaction
    Journal of Child Psychology and Psychiatry, 2008
    Co-Authors: Marieke E Altink, Alejandro Ariasvasquez, Barbara Franke, Dorine Slaatswillemse, Cathelijne J M Buschgens, Nanda Rommelse, Ellen A Fliers, Richard Anney
    Abstract:

    Background: The dopamine receptor D4 (DRD4) 7-Repeat Allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (G·E) interaction of the DRD4 7-Repeat Allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7-Repeat Allele differs between ADHD affected and unaffected children. Methods: Linear mixed models were used to assess main and interactive effects of the DRD4 7-Repeat Allele and smoking during pregnancy in 539 ADHD-affected children and their 407 unaffected siblings, aged 6–17 years. Results: There was some evidence pointing to differential effects of the DRD4 7-Repeat Allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for G·E interactions. Conclusion: Despite the large sample size, no G·E interactions were found. The impact of the DRD4 7-Repeat Allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in raterspecific behaviors. Keywords: Dopamine receptor D4 gene, attention deficit hyperactivity disorder (ADHD), maternal smoking during pregnancy, gene by environment interaction.

  • differential dopamine receptor d4 Allele association with adhd dependent of proband season of birth
    American Journal of Medical Genetics, 2008
    Co-Authors: Keeley J Brookes, Kate Langley, Anita Thapar, Michael Gill, Ziarih Hawi, Benjamin M Neale, X Xu, Jonathan Mill, E Taylor, Barbara Franke
    Abstract:

    Season of birth (SOB) has been associated with attention deficit hyperactivity disorder (ADHD) in two existing studies. One further study reported an interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It is important that these findings are further investigated to confirm or refute the findings. In this study, we investigated the SOB association with ADHD in four independent samples collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. We also observed a significant association with the 7-Repeat Allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this Allele between summer and winter seasons. Preferential transmission of the 2-repeat Allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of Alleles none of the SOB effects remained significant. We conclude that the DRD4 7-Repeat Allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD. Our findings suggest that we can refute a possible effect of SOB for ADHD.

Femmie Juffer - One of the best experts on this subject based on the ideXlab platform.

  • Effects of an attachment-based intervention on daily cortisol moderated by dopamine receptor D4: a randomized control trial on 1- to 3-year-olds screened for externalizing behavior.
    Development and Psychopathology, 2008
    Co-Authors: Marian J. Bakermans-kranenburg, Marinus H. Van Ijzendoorn, Judi Mesman, Lenneke R. A. Alink, Femmie Juffer
    Abstract:

    The effect of the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) on daily cortisol production was tested in a randomized controlled trial with 130 families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior. Six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline were conducted with individual families at their homes. Children in the intervention group showed lower cortisol levels, with a moderating role of the dopamine receptor D4 (DRD4) VNTR exon III polymorphism. The VIPP-SD program proved to be effective in decreasing daily cortisol production in children with the DRD4 7-Repeat Allele, but not in children without the DRD4 7-Repeat Allele. Our findings indicate that children are differentially susceptible to intervention effects dependent on the presence of the 7-Repeat DRD4 Allele.

  • experimental evidence for differential susceptibility dopamine d4 receptor polymorphism drd4 vntr moderates intervention effects on toddlers externalizing behavior in a randomized controlled trial
    Developmental Psychology, 2008
    Co-Authors: Marian J Bakermanskranenburg, Judi Mesman, Marinus H Van Ijzendoorn, Femke T A Pijlman, Femmie Juffer
    Abstract:

    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.