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

Henning Tiemeier*, Fleur P. Velders, Eszter Szekely, Sabine J. Roza, Gwen Dieleman, Vincent W.V. Jaddoe, Andre G. Uitterlinden, Tonya J.H. White, Marian J. Bakermans-Kranenburg, Albert Hofman, Marinus H. Van Ijzendoorn, James J. Hudziak, Frank C. Verhulst

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review

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 <.001) or postnatal anxiety symptoms (β = 1.64, 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.

Original languageEnglish
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume51
Issue number11
DOIs
Publication statusPublished - 1 Nov 2012
Externally publishedYes

Keywords

  • 5-HTTLPR
  • emotional problems
  • gene-environment interaction
  • Generation R
  • maternal anxiety

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