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

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Abstract

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/1-5 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 (β = 2.02, p < 0.001). Also, in children of mothers with prenatal anxiety symptoms, the s allele was associated with less accurate emotion-matching (β = -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. © 2012 American Academy of Child and Adolescent Psychiatry.

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Tiemeier, H., Velders, F. P., Szekely, E., Roza, S. J., Dieleman, G., Jaddoe, V. W. V., … Verhulst, F. C. (2012). 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. Journal of the American Academy of Child and Adolescent Psychiatry, 51(11). https://doi.org/10.1016/j.jaac.2012.08.021

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