The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring

A Soubry,Sk Murphy,W Demark-Wahnefried,C Hoyo,Jm Schildkraut,J Kurtzberg,F Wang,A Murtha,Rl Jirtle,Z Huang,Mr Forman

doi:10.1186/1868-7083-3-2

Abstract

In utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. Aberrant DNA methylation at the IGF2 and neighboring H19 DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436), as part of the Newborn Epigenetics Study (NEST). A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the H19 DMRs in newborns of African American (n = 177) but not Caucasian (n = 168) mothers who reported the use of antidepressive drugs during pregnancy (β = +6.89, p = 0.01). Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the IGF2 DMR (+3.05%, p = 0.01). In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the IGF2 DMRs in the offspring.

Highlights

Epigenetic mechanisms are important for regulating gene expression and differentiation during early life
We evaluate whether in utero exposure to maternal depression or intake of antidepressants is associated with variation in methylation at the two regulatory differentially methylated regions (DMRs) of the Insulin-like Growth Factor 2 (IGF2) imprinted domain
Our data suggest a race-specific influence of the use of antidepressive drugs on the methylation outcomes at the DMR upstream of H19, but not significantly at the IGF2 DMR

Summary

Introduction

Epigenetic mechanisms are important for regulating gene expression and differentiation during early life. In utero exposure to chemicals, nutrition, or social factors may change the methylation status at CpG-rich regions of gene promoter regions, causing permanent modification of gene expression patterns [1,2,3]. Such alterations may lead to increased risk of Maternal depression, and associated drug use are common exposures to the developing fetus. It has been shown that in utero exposure to maternal depression adversely affect fetal growth [10,11], fetal neurobehavioral development, or childhood behavior [12,13,14,15]. Treatment of psychiatric disorders during pregnancy is controversial; the fetus is either exposed to the psychotropic drugs or to the disease itself

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Conclusion