Impact of depression and stress on placental DNA methylation in ethnically diverse pregnant women

Epigenomics. 2021 Sep;13(18):1485-1496. doi: 10.2217/epi-2021-0192. Epub 2021 Sep 29.

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.

Plain language summary

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.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CpG Islands
  • DNA Methylation*
  • Depression / complications*
  • Depression / etiology*
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Placenta / metabolism*
  • Pregnancy
  • Pregnant People* / ethnology
  • Quantitative Trait Loci
  • Stress, Psychological / genetics*
  • Transcriptome
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT00912132