Variation in the Glucocorticoid Receptor Gene at rs41423247 Moderates the Effect of Prenatal Maternal Psychological Symptoms on Child Cortisol Reactivity and Behavior

Velders, Fleur P.; Dieleman, Gwen; Cents, Rolieke A. M.; Bakermans‐Kranenburg, Marian J.; Jaddoe, Vincent W. V.; Hofman, Albert; IJzendoorn, Marinus H. van; Verhulst, Frank C.; Tiemeier, Henning

doi:10.1038/npp.2012.118

Cited by 37 publications

(24 citation statements)

References 45 publications

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“…At first sight this strongly supports our present findings. Interestingly, Velders et al (2012) reported in contrast to the findings by Van Rossum et al (2006) and our findings that the C allele in combination with maternal psychological symptoms predicts emotional problems of the children at age of three. Given that these authors also investigated an interaction effect between rs41423247 and environmental influences on psychological health of the unborn child in later life (here age three), this contrary finding is especially noteworthy.…”

Section: Discussioncontrasting

confidence: 99%

“…There are several limitations to the present study: First of all, recent results by Velders et al (2012) yielded evidence that in the unborn child, rs41423247 interacts with maternal psychological health on emotional behavior and cortisol reactivity of the then born child at the age of three. At first sight this strongly supports our present findings.…”

Section: Discussionmentioning

confidence: 78%

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An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood

Montag¹,

Eichner²,

Markett³

et al. 2013

Front. Hum. Neurosci.

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The investigation of the interaction of genes and environment in the context of mental health and personality yields important new insights for a better understanding of human nature. Both antenatal and postnatal environmental factors have been considered as potential modulators of genetic activity. Antenatally, especially smoking or alcohol drinking habits of the mother dramatically influence the health of the child during pregnancy and even later on in life. In the present study we would like to introduce a more “distant” factor that is not under the control of the becoming mother but that nevertheless plays a potential role for the health of the unborn child later on in adulthood. Here, we retrospectively investigate the influence of solar activity (while the child is still in the uterus of the becoming mother) on brain structure (with a focus on hippocampus and amygdala volume) and personality in adulthood. We observe an interaction of a genetic variant (rs41423247) of the glucocorticoid receptor gene (NR3C1) and solar activity in the first trimester after conception on both hippocampal volume and the personality trait neuroticism in adulthood in N = 254 participants. The NR3C1 gene is the focus of interest, because of its influence on the hypothalamic-pituitary-adrenal (HPA) axis and negative emotionality. Carriers of the CC variant of rs41423247 grown in the womb under the influence of high sun radiation (high solar activity) show both the highest hippocampal volume in the left hemisphere and lowest neuroticism scores. The present findings should encourage researchers in psychology and psychiatry to include also environmental influences such as solar activity besides genetics to better understand the etiogenesis of psychiatric disorders.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 78%

An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood

Montag¹,

Eichner²,

Markett³

et al. 2013

Front. Hum. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Studies also identify the glucocorticoid receptor variants as moderators of stress reactivity and of developmental outcomes to environmental adversity (Kumsta et al, 2007; DeRijk et al, 2008; Bet et al, 2009; Kumsta et al, 2009; Manenschijn et al, 2009; van West et al, 2010; Velders et al, 2012). Based on this evidence, we hypothesized that glucocorticoid receptor variants would differentiate individuals with a “for better and for worse” sensitivity to environmental exposure (Belsky & Pluess, 2009), characterized by reduced rates of externalizing psychopathology in response to intervention and elevated rates in the absence of intervention.…”

Section: Introductionmentioning

confidence: 99%

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial

Albert¹,

Belsky²,

Crowley³

et al. 2015

J Policy Anal Manage

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Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track Randomized Control Trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.

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“…At the level of psychopathology, NR3C1 variants are associated with child-onset mood disorder (Mill et al, 2009), adolescent alcohol abuse (Desrivieres et al, 2011), and adult major depression (van Rossum et al, 2006; van West et al, 2006; Zobel et al, 2008). NR3C1 variants have also been associated with differential response to environmental exposure, including greater incidence of depression among individuals exposed to adversity (Bet et al, 2009) and irregular cortisol reactivity and behavior problems among the offspring of mothers with prenatal psychological symptoms (Velders et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Developmental mediation of genetic variation in response to the Fast Track prevention program

et al. 2015

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We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment with a range of services and resources provided to the children and their families and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants’ risk of externalizing psychopathology at age 25 years was moderated by a variant in the Glucocorticoid Receptor Gene (NR3C1). Children who carried copies of the A-allele of the single-nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for-better-and-for-worse gene-by-intervention interaction (GxI): That the observed GxI effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European-American children in the Fast Track RCT with available genetic information (129 intervention children and 141 control-group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of “for-better-and-for-worse” susceptibility to intervention observed at the age-25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high-school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention, and worse adjustment among children in the control condition. In turn, these proximal GxI effects early in development mediated the ultimate GxI effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention.

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Variation in the Glucocorticoid Receptor Gene at rs41423247 Moderates the Effect of Prenatal Maternal Psychological Symptoms on Child Cortisol Reactivity and Behavior

Cited by 37 publications

References 45 publications

An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood

An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial

Developmental mediation of genetic variation in response to the Fast Track prevention program

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