title: 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.
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.
  
  
  METHODS
  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/1½-5 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.
authors.affiliation: Erasmus Medical Center (MC)-Sophia Children's Hospital, Rotterdam, and the Generation R Study Group at Erasmus MC, Rotterdam. h.tiemeier@erasmusmc.nl
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.forename: Fleur P
authors.initials: FP
authors.lastname: Velders
authors.forename: Eszter
authors.initials: E
authors.lastname: Szekely
authors.forename: Sabine J
authors.initials: SJ
authors.lastname: Roza
authors.forename: Gwen
authors.initials: G
authors.lastname: Dieleman
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Tonya J H
authors.initials: TJ
authors.lastname: White
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Bakermans-Kranenburg
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Marinus H
authors.initials: MH
authors.lastname: Van Ijzendoorn
authors.forename: James J
authors.initials: JJ
authors.lastname: Hudziak
authors.forename: Frank C
authors.initials: FC
authors.lastname: Verhulst
mesh_terms: D000328:Adult; D002648:Child; D002657:Child Development / Q000502:physiology*; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology*; D059647:Gene-Environment Interaction; D006801:Humans; D009035:Mothers / Q000523:psychology; D009426:Netherlands / Q000453:epidemiology; D011159:Population Surveillance; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000235:genetics / Q000523:psychology; D012107:Research Design / Q000592:standards* / Q000639:trends; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins