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Published Online: 25 March 2016

Distress During Pregnancy: Epigenetic Regulation of Placenta Glucocorticoid-Related Genes and Fetal Neurobehavior

Catherine Monk, Ph.D., Tianshu Feng, M.S., Seonjoo Lee, Ph.D., Izabela Krupska, M.A., Frances A. Champagne, Ph.D., and Benjamin Tycko, M.D., Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 173, Number 7
https://doi.org/10.1176/appi.ajp.2015.15091171
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Abstract

Objective:

Increased risk of psychopathology is observed in children exposed to maternal prenatal distress, and elevated maternal cortisol and epigenetic regulation of placental glucocorticoid-pathway genes are potential mechanisms. The authors examined maternal distress and salivary cortisol in relation to fetal movement and heart rate (“coupling”) and DNA methylation of three glucocorticoid pathway genes—HSD11B2, NR3C1, and FKBP5—in term placentas.

Method:

Mood questionnaires and salivary cortisol were collected from 61 women between 24–27 gestational weeks, and fetal assessment was conducted at 34–37 weeks. Placental CpG methylation in the three genes was analyzed using 450K Beadchips and bisulfite sequencing; correlations between maternal and fetal variables and DNA methylation were tested; and maternal distress effects on fetal behavior via DNA methylation were investigated.

Results:

Perceived stress (Perceived Stress Scale), but not cortisol, was associated with altered CpG methylation in placentas. In the highest tertile of the Perceived Stress Scale, the Beadchip data revealed modestly elevated methylation of HSD11B2, associated with lower fetal coupling (β=−0.51), and modestly elevated methylation of FKBP5, also with lower fetal coupling (β=−0.47). These increases in methylation were validated by bisulfite sequencing, where they occurred in a minority of clones.

Conclusions:

This is the first study to link the effects of pregnant women's distress on the fetus and epigenetic changes in placental genes. Since increased DNA methylation in HSD11B2 and FKBP5 are seen in a minority of bisulfite sequencing clones, these epigenetic changes, and functional consequences, may affect subpopulations of placental cells.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
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American Journal of Psychiatry
Volume 173 • Number 7 • July 01, 2016
Pages: 705 - 713
PubMed: 27013342

History

Received: 13 September 2015
Revision received: 16 November 2015
Accepted: 3 December 2015
Published online: 25 March 2016
Published in print: July 01, 2016

Authors

Details

Catherine Monk, Ph.D.
From the Department of Psychiatry, Columbia University Medical Center, New York; New York State Psychiatric Institute, New York; the Department of Obstetrics and Gynecology, Columbia University Medical Center, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York; Institute for Cancer Genetics, Columbia University Medical Center, New York; the Department of Psychology, Columbia University, New York; and the Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
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Tianshu Feng, M.S.
From the Department of Psychiatry, Columbia University Medical Center, New York; New York State Psychiatric Institute, New York; the Department of Obstetrics and Gynecology, Columbia University Medical Center, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York; Institute for Cancer Genetics, Columbia University Medical Center, New York; the Department of Psychology, Columbia University, New York; and the Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
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Seonjoo Lee, Ph.D.
From the Department of Psychiatry, Columbia University Medical Center, New York; New York State Psychiatric Institute, New York; the Department of Obstetrics and Gynecology, Columbia University Medical Center, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York; Institute for Cancer Genetics, Columbia University Medical Center, New York; the Department of Psychology, Columbia University, New York; and the Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
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Izabela Krupska, M.A.
From the Department of Psychiatry, Columbia University Medical Center, New York; New York State Psychiatric Institute, New York; the Department of Obstetrics and Gynecology, Columbia University Medical Center, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York; Institute for Cancer Genetics, Columbia University Medical Center, New York; the Department of Psychology, Columbia University, New York; and the Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
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Frances A. Champagne, Ph.D.
From the Department of Psychiatry, Columbia University Medical Center, New York; New York State Psychiatric Institute, New York; the Department of Obstetrics and Gynecology, Columbia University Medical Center, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York; Institute for Cancer Genetics, Columbia University Medical Center, New York; the Department of Psychology, Columbia University, New York; and the Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
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Benjamin Tycko, M.D., Ph.D.
From the Department of Psychiatry, Columbia University Medical Center, New York; New York State Psychiatric Institute, New York; the Department of Obstetrics and Gynecology, Columbia University Medical Center, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York; Institute for Cancer Genetics, Columbia University Medical Center, New York; the Department of Psychology, Columbia University, New York; and the Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
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Notes

Address correspondence to Dr. Monk ([email protected]).
Previously presented at the Annual Conference of Biological Psychiatry, Toronto, May 13–15, 2015.

Competing Interests

The authors report no financial relationships with commercial interests.

Funding Information

National Institute of Mental Health10.13039/100000025: NIMH R01 MH092580
Supported by NIMH grant R01 MH092580 (to Dr. Monk, Champagne, Tycko).

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