Impact of Depression and Stress on Placental DNA Methylation in Ethnically Diverse Pregnant Women

Abstract

Aim: To investigate the association between placental genome-wide methylation at birth and antenatal depression and stress during pregnancy. Methods: We examined the association between placental genome-wide DNA methylation (n = 301) and maternal depression and stress assessed at six gestation periods during pregnancy. Correlation between DNA methylation at the significantly associated CpGs and expression of nearby genes in the placenta was tested. Results: Depression and stress were associated with methylation of 16 CpGs and two CpGs, respectively, at a 5% false discovery rate. Methylation levels at two of the CpGs associated with depression were significantly associated with expression of ADAM23 and CTDP1, genes implicated in neurodevelopment and neuropsychiatric diseases. Conclusion: Placental epigenetic changes linked to antenatal depression suggest potential fetal brain programming.

Clinical trial registration number: NCT00912132 (ClinicalTrials.gov)

Lay abstract

Our research examined 301 women at six time points during their pregnancies in regard to depression or stress. We then examined samples of the placenta after birth for epigenetic changes and explored whether they were linked to the status of depression or stress observed during pregnancy. We found that 16 epigenetic changes were linked to depression and two were linked to stress. Some of the epigenetic changes in the placenta linked to depression were located close to genes which are known to have important roles in brain development and occurrence of psychiatric disorders. Therefore maternal depression may have implications for the long-term mental health of the child.

Keywords::

• biological markers
• depression
• gene–environment
• postpartum
• pregnancy
• stress

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0192

Author contributions

M Tesfaye, F Tekola-Ayele and P Joseph conceived and designed this study; M Tesfaye and X Zeng performed statistical analyses; S Chatterjee helped with statistical methodology; M Tesfaye wrote the draft manuscript. All authors contributed to the interpretation of the findings, provided critical intellectual content and approved the final manuscript.

Acknowledgments

The authors wish to thank T Workalemahu for their help with IPA. The authors wish to thank research teams at all participating clinical centers (which include Christina Care Health Systems; Columbia University; Fountain Valley Hospital, California; Long Beach Memorial Medical Center; New York Hospital, Queens; Northwestern University; University of Alabama at Birmingham; University of California, Irvine; Medical University of South Carolina; Saint Peters University Hospital; Tufts University and Women and Infants Hospital of Rhode Island). The authors also acknowledge the Wadsworth Center, C-TASC and The EMMES Corporations in providing data and imaging support. This work utilized the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov).

Financial & competing interests disclosure

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, including American Recovery and Reinvestment Act funding via contract numbers: HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C and HHSN27500008. Additional support was obtained from the National Institute on Minority Health and Health Disparities and the National Institute of Diabetes and Digestive and Kidney Diseases. P Joseph is supported by the National Institute of Nursing Research (1ZIANR000035-01), the Office of Workforce Diversity and the NIH Distinguished Scholars Award, and by the Rockefeller University Heilbrunn Nurse Scholar Award. M Tesfaye received Intramural Research Training Award, National Institute of Nursing Research, African Postdoctoral Training Initiative, NIH and Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The authors certify that this manuscript reports the secondary analysis of clinical trial data that have been shared with them, and that the use of this shared data is in accordance with the terms (if any) agreed upon their receipt. The source of this data is: NCT00912132. The placental DNA methylation, genotype, and gene expression data are available through dbGaP with accession number phs001717.v1.p1. The analytic codes for the current study are available upon request to the corresponding author.

Additional information

Funding

This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, including American Recovery and Reinvestment Act funding via contract numbers: HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C and HHSN27500008. Additional support was obtained from the National Institute on Minority Health and Health Disparities and the National Institute of Diabetes and Digestive and Kidney Diseases. P Joseph is supported by the National Institute of Nursing Research (1ZIANR000035-01), the Office of Workforce Diversity and the NIH Distinguished Scholars Award, and by the Rockefeller University Heilbrunn Nurse Scholar Award. M Tesfaye received Intramural Research Training Award, National Institute of Nursing Research, African Postdoctoral Training Initiative, NIH and Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.