scholarly journals Maternal care of heterozygous dopamine receptor D4 knockout mice: Differential susceptibility to early‐life rearing conditions

2020 ◽  
Vol 19 (7) ◽  
Author(s):  
Jelle Knop ◽  
Marinus H. IJzendoorn ◽  
Marian J. Bakermans‐Kranenburg ◽  
Marian Joëls ◽  
Rixt Veen
Keyword(s):  
Dopamine Receptor ◽  
Knockout Mice ◽  
Maternal Care ◽  
Early Life ◽  
Differential Susceptibility ◽  
Rearing Conditions ◽  
Dopamine Receptor D4

scholarly journals Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

2019 ◽  
Author(s):  
Jelle Knop ◽  
Marinus H. van IJzendoorn ◽  
Marian J. Bakermans-Kranenburg ◽  
Marian Joëls ◽  
Rixt van der Veen
Keyword(s):  
Dopamine Receptor ◽  
Maternal Care ◽  
Environmental Control ◽  
Animal Experiments ◽  
Differential Susceptibility ◽  
Female Offspring ◽  
Negative Effects ◽  
Rearing Conditions ◽  
Puberty Onset ◽  
Dopamine Receptor D4

AbstractThe differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7-repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4+/- mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2-14. Puberty onset was examined from P24-P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4+/- mice exhibited the lowest and CN reared Drd4+/- mice the highest levels of licking/grooming. These results indicate that both genetic and early-environmental factors play an important role in shaping maternal care of the offspring for better and for worse.

scholarly journals The effects of different rearing conditions on sexual maturation and maternal care in heterozygous mineralocorticoid receptor knockout mice

2019 ◽  
Vol 112 ◽  
pp. 54-64 ◽  
Author(s):  
Jelle Knop ◽  
Marinus H. van IJzendoorn ◽  
Marian J. Bakermans-Kranenburg ◽  
Marian Joëls ◽  
Rixt van der Veen
Keyword(s):  
Sexual Maturation ◽  
Knockout Mice ◽  
Maternal Care ◽  
Mineralocorticoid Receptor ◽  
Rearing Conditions

Genetic differential susceptibility in literacy-delayed children: A randomized controlled trial on emergent literacy in kindergarten

2015 ◽  
Vol 27 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Rachel D. Plak ◽  
Cornelia A. T. Kegel ◽  
Adriana G. Bus
Keyword(s):  
Randomized Controlled Trial ◽  
Dopamine Receptor ◽  
Text Comprehension ◽  
Controlled Trial ◽  
Differential Susceptibility ◽  
Educational Interventions ◽  
Kindergarten Children ◽  
National Standard ◽  
Randomized Controlled ◽  
Dopamine Receptor D4

AbstractIn this randomized controlled trial, 508 5-year-old kindergarten children participated, of whom 257 were delayed in literacy skills because they belonged to the lowest quartile of a national standard literacy test. We tested the hypothesis that some children are more susceptible to school-entry educational interventions than their peers due to their genetic makeup, and thus whether the dopamine receptor D4 gene moderated intervention effects. Children were randomly assigned to a control condition or one of two interventions involving computer programs tailored to the literacy needs of delayed pupils: Living Letters for alphabetic knowledge and Living Books for text comprehension. Effects of Living Books met the criteria of differential susceptibility. For carriers of the dopamine receptor D4 gene seven-repeat allele (about one-third of the delayed group), the Living Books program was an important addition to the common core curriculum in kindergarten (effect size d = 0.56), whereas the program did not affect the other children (d = –0.09). The same seven-repeat carriers benefited more from Living Letters than did the noncarriers, as reflected in effect sizes of 0.63 and 0.34, respectively, although such differences did not fulfill the statistical criteria for differential susceptibility. The implications of differential susceptibility for education and regarding the crucial question “what works for whom?” are discussed.

Heritability of children's prosocial behavior and differential susceptibility to parenting by variation in the dopamine receptor D4 gene

2011 ◽  
Vol 23 (1) ◽  
pp. 53-67 ◽  
Author(s):  
Ariel Knafo ◽  
Salomon Israel ◽  
Richard P. Ebstein
Keyword(s):  
Prosocial Behavior ◽  
Dopamine Receptor ◽  
Parental Influence ◽  
Molecular Genetic ◽  
Differential Susceptibility ◽  
Differential Sensitivity ◽  
Repeat Allele ◽  
Children's Behavior ◽  
Genes And Environment ◽  
Dopamine Receptor D4

AbstractTheoretical considerations and new empirical evidence suggest that children's development cannot simply be explained by either genes or environment but that their interaction is important to understanding child behavior. In particular, a genetic polymorphism, the exon III repeat region of the dopamine receptor D4, has been the focus of interest regarding differential susceptibility to parental influence. To study environmental and genetic influences on children's prosocial behavior, 168 twin pairs (mean age = 44 months) participated in an experiment that assessed prosocial behavior via three measures: compliant prosocial behavior elicited in response to social requests, self-initiated prosocial behavior enacted voluntarily, and mothers' rating of children's behavior. Genetic effects accounted for 34% to 53% of the variance in prosocial behavior. The rest of the variance was accounted for by nonshared environment and error. Parenting measures of maternal positivity, negativity, and unexplained punishment did not correlate significantly with children's prosocial behavior. However, when parenting was stratified by presence or absence of the child's dopamine receptor D4 7-repeat allele in an overlapping sample of 167 children to model differential susceptibility to parental influence, a richer picture emerged. Positive parenting related meaningfully to mother-rated prosocial behavior, and unexplained punishment related positively to self-initiated prosocial behavior, but only among children carrying the 7-repeat allele. The findings demonstrate that a molecular genetic strategy, based on genotyping of common polymorphisms and combined with a classic twin approach, provides a richer description of how genes and environment interact to shape children's behavior, and allows for the identification of differential sensitivity to parental influence.

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

2015 ◽  
Vol 27 (1) ◽  
pp. 151-162 ◽  
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.

Genetic polymorphism of dopamine receptor D4 (DRD4) gene in ten Indian rhesus macaques (Macaca mulatta mulatta)

Meta Gene ◽  
2021 ◽  
pp. 100891
Author(s):  
Sanjoy Kumar Chatterjee ◽  
Suniti Yadav ◽  
Kallur Nava Saraswathy ◽  
Prakash Ranjan Mondal
Keyword(s):  
Genetic Polymorphism ◽  
Dopamine Receptor ◽  
Macaca Mulatta ◽  
Rhesus Macaques ◽  
Drd4 Gene ◽  
Dopamine Receptor D4

scholarly journals Three-way interaction effects of early life stress, positive parenting and FKBP5 in the development of depressive symptoms in a general population

2021 ◽  
Author(s):  
Rebecka Keijser ◽  
Susanne Olofsdotter ◽  
Kent W. Nilsson ◽  
Cecilia Åslund
Keyword(s):  
Young Adults ◽  
Depressive Symptoms ◽  
Life Stress ◽  
Early Life ◽  
Differential Susceptibility ◽  
Early Life Stress ◽  
Interaction Effects ◽  
Positive Parenting ◽  
Depressive Symptomology ◽  
Patterns Of Interaction

AbstractFKBP5 gene–environment interaction (cG × E) studies have shown diverse results, some indicating significant interaction effects between the gene and environmental stressors on depression, while others lack such results. Moreover, FKBP5 has a potential role in the diathesis stress and differential susceptibility theorem. The aim of the present study was to evaluate whether a cG × E interaction effect of FKBP5 single-nucleotide polymorphisms (SNPs) or haplotype and early life stress (ELS) on depressive symptoms among young adults was moderated by a positive parenting style (PASCQpos), through the frameworks of the diathesis stress and differential susceptibility theorem. Data were obtained from the Survey of Adolescent Life in Västmanland Cohort Study, including 1006 participants and their guardians. Data were collected during 2012, when the participants were 13 and 15 years old (Wave I: DNA), 2015, when participants were 16 and 18 years old (Wave II: PASCQpos, depressive symptomology and ELS) and 2018, when participants were 19 and 21 years old (Wave III: depressive symptomology). Significant three-way interactions were found for the FKBP5 SNPs rs1360780, rs4713916, rs7748266 and rs9394309, moderated by ELS and PASCQpos, on depressive symptoms among young adults. Diathesis stress patterns of interaction were observed for the FKBP5 SNPs rs1360780, rs4713916 and rs9394309, and differential susceptibility patterns of interaction were observed for the FKBP5 SNP rs7748266. Findings emphasize the possible role of FKBP5 in the development of depressive symptoms among young adults and contribute to the understanding of possible differential susceptibility effects of FKBP5.

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