Abstract
Prenatal maternal psychopathology affects child development, but some children seem more vulnerable than others. Genetic variance in hypothalamic–pituitary–adrenal axis genes may influence the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems. This hypothesis was tested in the Generation R Study, a population-based cohort from fetal life onward. In total, 1727 children of Northern European descent and their mothers participated in this study and were genotyped for variants in the glucocorticoid receptor (GR) gene (rs6189/rs6190, rs10052957, rs41423247, rs6195, and rs6198) and the FK506-binding protein 5 (FKBP5) gene (rs1360780). Prenatal maternal psychological symptoms were assessed at 20 weeks pregnancy and child behavior was assessed by both parents at 3 years. In a subsample of 331 children, data about cortisol reactivity were available. Based on power calculations, only those genetic variants with sufficient minor allele frequencies (rs41423247, rs10052957, and rs1360780) were included in the interaction analyses. We found that variation in GR at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems (beta 0.41, SE 0.16, p=0.009). This prenatal interaction effect was independent of mother's genotype and maternal postnatal psychopathology, and not found for prenatal psychological symptoms of the father. Moreover, the interaction between rs41423247 and prenatal psychological symptoms was also associated with decreased child cortisol reactivity (beta −2.30, p-value 0.05). These findings emphasize the potential effect of prenatal gene–environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems.
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Acknowledgements
The Generation R Study is conducted by the Erasmus Medical Centre in close collaboration with the Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam, and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge all participants and the contribution of general practitioners, hospitals, midwives and pharmacies in Rotterdam. The first phase of the Generation R Study is made possible by financial support from: Erasmus Medical Centre, Rotterdam, Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development (ZonMw). This study was supported by a grant from the Sophia Foundation for Scientific Research (SKZ Foundation) (Grant no.491) and ZonMw (Grant no.10.000.1003). MHvIJ and MJB-K were supported by research awards from the Netherlands Organization for Scientific Research (MHvIJ: NWO SPINOZA prize; MJBK: VICI Grant no. 453-09-003). HT was supported by NWO-grant 017.106.370 (VIDI).
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The authors declare no conflict of interest. Professor Dr FCV is a contributing author of the Achenbach System of Emperically Based Assessments, from which he receives remuneration.
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Velders, F., Dieleman, G., Cents, R. et al. Variation in the Glucocorticoid Receptor Gene at rs41423247 Moderates the Effect of Prenatal Maternal Psychological Symptoms on Child Cortisol Reactivity and Behavior. Neuropsychopharmacol 37, 2541–2549 (2012). https://doi.org/10.1038/npp.2012.118
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DOI: https://doi.org/10.1038/npp.2012.118
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