Cents, R.A.M.

Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior (Article)

2012-10-01T00:00:00Z

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, p0.009). 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.

Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior (Article)

2012-10-01T00:00:00Z

Grandparental anxiety and depression predict young children's internalizing and externalizing problems. The generation R study (Article)

2010-01-01T00:00:00Z

Background: Family history is a major risk factor for child problem behaviour, yet few studies have examined the association between grandparental psychiatric disorder and child problem behaviour. Results are inconsistent as to whether the effect of grandparental depression on child problem behaviour is independent of parental psychopathology. Methods: Mothers and their children participated in an ethnically Dutch subcohort of a population-based prospective cohort in the Netherlands. N = 816 (66%) mothers and n = 691 fathers participated in the prenatal interviews. N = 687 (84%) mothers and children and n = 565 (82%) fathers participated three years postpartum. (Grand)parental psychopathology was assessed during pregnancy of the mothers with the Family Informant Schedule and Criteria (FISC), the Composite International Diagnostic Interview (CIDI) and the Brief Symptom Inventory (BSI). Child behaviour was assessed with the Child Behavior Checklist (CBCL) by mother and father when the child was three years old. Results: Grandparental anxiety disorder predicted maternal reports of children's internalizing problems (OR = 1.98, 95% C.I. (1.20, 3.28), p-value < 0.01) and externalizing problems (OR = 1.73, 95% C.I. (1.04, 2.87), p-value = 0.03), independent of parental psychopathology. Results were similar for grandparental depression; internalizing OR = 1.75, 95% C.I (1.11, 2.75), p-value = 0.02 and externalizing OR = 1.67, 95% C.I. (1.05, 2.64) p-value = 0.03. However, grandparental psychopathology was not associated with children's problem behaviour as reported by the father. Limitations: Information on grandparental lifetime psychiatric disorder was assessed through a parental interview which may have led to an underestimation of the prevalence rates. Conclusions: These results confirm the importance of a family history including not only the parental but also the grandparental generations.