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 - 25/10/12
, Fleur P. Velders, M.D. a, Eszter Szekely, M.Sc. a, Sabine J. Roza, M.D., Ph.D. b, Gwen Dieleman, M.D. b, Vincent W.V. Jaddoe, M.D., Ph.D. a, Andre G. Uitterlinden, Ph.D. c, Tonya J.H. White, M.D., Ph.D. b, Marian J. Bakermans-Kranenburg, Ph.D. d, Albert Hofman, M.D., Ph.D. c, Marinus H. Van IJzendoorn, M.D., Ph.D. e, James J. Hudziak, M.D. f, Frank C. Verhulst, M.D., Ph.D. b
Correspondence to: Henning Tiemeier, Department of Child and Adolescent Psychiatry and Psychology, Erasmus Medical Center–Sophia Children's Hospital, P.O. Box 2060, 3000 CB RotterdamRiassunto |
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/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.
Il testo completo di questo articolo è disponibile in PDF.Key Words : Generation R, 5-HTTLPR, maternal anxiety, gene–environment interaction, emotional problems
Mappa
| This article was reviewed under and accepted by Ad Hoc Editor Daniel S. Pine, M.D. |
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| Drs. Tiemeier and Velders contributed equally to this research. |
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| The first phase of the Generation R Study is made possible by financial support from: Erasmus Medical Centre, Rotterdam, Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development (ZonMw). The present study was supported by grants from the Sophia Foundation for Scientific Research (SKZ Foundation) (491 and 514) and ZonMw (10.000.1003). Further support was obtained from the Netherlands Organization for Scientific Research: NWO-grants 452-04-306 and 453-09-003 (VIDI and VICI) to M.J.B.-K., 017.106.370 (VIDI) to H.T., and SPINOZA prize to M.H.vIJ. |
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| This article will be part of a special series on recent findings and progress in the fields of birth cohort and longitudinal studies of child and adolescent psychopathology. This special series is intended to showcase some of the most important new findings and promising leads in the study of developmental psychopathology over time, and to demonstrate the Journal's renewed commitment to publishing the highest quality articles on the topic. Each article is in part a review of the most important findings to date from the study and in part original research to allow readers to learn about a new research finding with a more complete context of the study than is usually possible. |
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| The Generation R Study is conducted by the Erasmus MC in close collaboration with the Erasmus University Rotterdam, and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. |
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| Disclosure: Dr. Hudziak will be the coauthor of an editorial on this article in an upcoming issue. He has received funding from the National Institute of Mental Health and the National Institute of Diabetes and Digestive and Kidney Disease. His primary appointment is with the University of Vermont. He has additional appointments with Erasmus University in Rotterdam, Vrije University in Amsterdam, Dartmouth Medical School in Hanover, New Hampshire, and Avera Institute of Human Behavioral Genetics in Sioux Falls, South Dakota. Dr. Verhulst publishes the Dutch translations of the Achenbach System of Empirically Based Assessment. Drs. Tiemeier, Velders, Szekely, Roza, Dieleman, Jaddoe, Uitterlinden, White, Bakermans-Kranenburg, Hofman, and Van IJzendoorn report no biomedical financial interests or potential conflicts of interest. |
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| This article will be discussed in an editorial by Drs. James J. Hudziak and Douglas K. Novins in an upcoming issue. |
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| Supplemental material cited in this article is available online. |
Vol 51 - N° 11
P. 1119 - novembre 2012 Ritorno al numero
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