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Research Paper

The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior

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Pages 1321-1329 | Received 20 Jun 2013, Accepted 26 Sep 2013, Published online: 17 Oct 2013
 

Abstract

Exposure to maternal mood disorder in utero may program infant neurobehavior via DNA methylation of the glucocorticoid receptor (NR3C1) and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), two placental genes that have been implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA) axis. We tested the relations among prenatal exposure to maternal depression or anxiety, methylation of exon 1F of NR3C1 and 11β-HSD-2, and newborn neurobehavior. Controlling for relevant covariates, infants whose mothers reported depression during pregnancy and showed greater methylation of placental NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than infants whose mothers did not report depression. On the other hand, infants whose mothers reported anxiety during pregnancy and showed greater methylation of placental 11β-HSD-2 CpG4 were more hypotonic compared with infants of mothers who did not report anxiety during pregnancy. Our results support the fetal programming hypothesis and suggest that fetal adjustments to cues from the intrauterine environment, in this case an environment that could be characterized by increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.

10.4161/epi.26634

Potential Conflicts of Interest

The authors report no conflict of interest.

Financial Disclosure

This study was supported by the National Institute of Mental Health R01MH094609 (to Marsit CJ) and a National Research Service Award from the National Institute on Drug Abuse F32DA032175 (to Conradt E). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, National Institute on Drug Abuse, or the National Institutes of Health.

Acknowledgments

We would like to thank Gilda Ferro, Joyce Lee, Erica Oliveria, and Susan Capobianco for their hard work in recruitment of subjects and the support and staff of the Brown Center for the Study of Children at Risk.

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