The Generation R Study: A Review of Design, Findings to Date, and a Study of the 5-HTTLPR by Environmental Interaction From Fetal Life Onward

Objective: First, we give an overview of child psychiatric research in the Generation R Study, a population-based cohort from fetal life forward. Second, we examine within Generation R whether the functional polymorphism (5-HTTLPR) in the promoter of the serotonin transporter gene interacts with prenatal maternal chronic difficulties, prenatal maternal anxiety or postnatal maternal anxiety to influence child emotional development. Method: A total of 2,136 northern European children were genotyped for 5-HTTLPR and,rs25531. Mothers reported chronic difficulties and anxiety symptoms at 20 weeks' pregnancy and when the child was 3 years old. Child emotion recognition was observed at 3 years, and child emotional problems were assessed with the CBCL/11/2-5 at 5 years. Results: There were consistent main effects of maternal difficulties and anxiety on child emotional problems, but no main effect of 5-HTTLPR. Moreover, children with the s allele were at increased risk for emotional problems if their mothers reported prenatal anxiety symptoms (beta = 2.02, p < .001) or postnatal anxiety symptoms (beta = 1.64, p < 0.001). Also, in children of mothers with prenatal anxiety symptoms, the s allele was associated with less accurate emotion-matching (beta = -0.11, p = .004). Conclusions: This population-based study shows that vulnerability due to 5-HTTLPR is not specific for certain adverse exposures or severe events, but suggests that the small effects of gene environment interaction on emotional development become manifest early in life. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(11):1119-1135.