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Article

Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children’s Behavioral Measures

1
Schizophrenia and Neurodevelopmental Disorders Research Section, Douglas Hospital Research Centre, Montreal, QC H4H 1R3, Canada
2
Department of Cognitive Neuropsychology, Tilburg University, 5037 AB Tilburg, The Netherlands
3
Genome Analysis Group, Leibniz Institute on Aging—Fritz Lipmann Institute, 07745 Jena, Germany
4
Rehabilitation Research Center, Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, 3500 Hasselt, Belgium
5
Family Care, Department of Personal and Preventive Care, Philips Research, 5656 AE Eindhoven, The Netherlands
6
Hans Berger Department of Neurology, Jena University Hospital, 07740 Jena, Germany
7
Health Psychology Research Group, University of Leuven (KU Leuven), 3000 Leuven, Belgium
8
Department of Welfare, Public Health and Family, Flemish Government, 1030 Brussels, Belgium
*
Author to whom correspondence should be addressed.
Authors contributed equally to this work.
Academic Editor: Shigemi Matsuyama
Cells 2021, 10(9), 2421; https://doi.org/10.3390/cells10092421
Received: 18 June 2021 / Revised: 3 September 2021 / Accepted: 8 September 2021 / Published: 14 September 2021
Epigenetic changes are associated with altered behavior and neuropsychiatric disorders and they modify the trajectory of aging. Maternal anxiety during pregnancy is a common environmental challenge for the fetus, causing changes in DNA methylation. Here, we determined the mediating role of DNA methylation and the moderating role of offspring sex on the association between maternal anxiety and children’s behavioral measures. In 83 mother–child dyads, maternal anxiety was assessed in each trimester of pregnancy when the child was four years of age. Children’s behavioral measures and children’s buccal DNA methylation levels (NR3C1, IGF2/H19 ICR, and LINE1) were examined. Higher maternal anxiety during the third trimester was associated with more methylation levels of the NR3C1. Moderating effects of sex on the association between maternal anxiety and methylation were found for IGF2/H19 and LINE1 CpGs. Mediation analysis showed that methylation of NR3C1 could buffer the effects of maternal anxiety on children’s behavioral measures, but this effect did not remain significant after controlling for covariates. In conclusion, our data support an association between maternal anxiety during pregnancy and DNA methylation. The results also underscore the importance of sex differences and timing effects. However, DNA methylation as underlying mechanism of the effect of maternal anxiety during pregnancy on offspring’s behavioral measures was not supported. View Full-Text
Keywords: DNA methylation; NR3C1; IGF2/H19; LINE1; maternal anxiety; interaction; mediation; sex-specific effects DNA methylation; NR3C1; IGF2/H19; LINE1; maternal anxiety; interaction; mediation; sex-specific effects
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MDPI and ACS Style

Cao-Lei, L.; van den Heuvel, M.I.; Huse, K.; Platzer, M.; Elgbeili, G.; Braeken, M.A.K.A.; Otte, R.A.; Witte, O.W.; Schwab, M.; Van den Bergh, B.R.H. Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children’s Behavioral Measures. Cells 2021, 10, 2421. https://doi.org/10.3390/cells10092421

AMA Style

Cao-Lei L, van den Heuvel MI, Huse K, Platzer M, Elgbeili G, Braeken MAKA, Otte RA, Witte OW, Schwab M, Van den Bergh BRH. Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children’s Behavioral Measures. Cells. 2021; 10(9):2421. https://doi.org/10.3390/cells10092421

Chicago/Turabian Style

Cao-Lei, Lei, Marion I. van den Heuvel, Klaus Huse, Matthias Platzer, Guillaume Elgbeili, Marijke A.K.A. Braeken, Renée A. Otte, Otto W. Witte, Matthias Schwab, and Bea R.H. Van den Bergh 2021. "Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children’s Behavioral Measures" Cells 10, no. 9: 2421. https://doi.org/10.3390/cells10092421

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