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).

Keywords: biological markers; depression; gene–environment; postpartum; pregnancy; stress.

Conflict of interest statement

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.

Figures

Figure 1.. Latent class trajectory for Edinburgh Postnatal Depression Scale scores of pregnant women of the fetal growth studies across six time point assessments.

Figure 2.. Latent class trajectory for Cohen’s Perceived Stress Scale scores of pregnant women of the fetal growth studies across six time point assessments.

Figure 3.. Correlations between placental expression of (A) CPE, (B) ADAM23, (C) CTDP1 and (D) LOC105377590 and DNA methylation levels of depression-associated CpGs.