Association Between Maternal Perinatal Stress and Depression on Infant DNA Methylation in the First Year of Life

Overview

Journal Res Sq

Date 2024 Apr 2

PMID 38562779

Authors

Sarina Abrishamcar

Beryl Zhuang

Mara Thomas

Nicole Gladish

Julia MacIsaac

Meaghan Jones

Elinor Simons

Theo Moraes

Piush Mandhane

Jeffrey Brook

Padmaja Subbarao

Stuart Turvey

Edith Chen

Gregory Miller

Michael Kobor

Anke Huels

Affiliations

Soon will be listed here.

Abstract

Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with changes in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with changes in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To investigate the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including , and have been implicated in adverse fetal outcomes and neuropsychiatric disorders. This suggested that differential DNAm may play a role in the relationship between maternal mental health and child health.

References

Oberlander T, Weinberg J, Papsdorf M, Grunau R, Misri S, Devlin A . Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3(2):97-106. DOI: 10.4161/epi.3.2.6034. View

Ruehlmann A, Sammallahti S, Cortes Hidalgo A, Bakulski K, Binder E, Campbell M . Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation. Mol Psychiatry. 2023; 28(12):5090-5100. DOI: 10.1038/s41380-023-02010-5. View

Yamada T, Sakisaka T, Hisata S, Baba T, Takai Y . RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho. J Biol Chem. 2005; 280(38):33026-34. DOI: 10.1074/jbc.M504587200. View

Breton C, Marsit C, Faustman E, Nadeau K, Goodrich J, Dolinoy D . Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environ Health Perspect. 2017; 125(4):511-526. PMC: 5382002. DOI: 10.1289/EHP595. View

Kappil M, Lambertini L, Chen J . Environmental Influences on Genomic Imprinting. Curr Environ Health Rep. 2015; 2(2):155-62. PMC: 4443909. DOI: 10.1007/s40572-015-0046-z. View

Grote N, Bridge J, Gavin A, Melville J, Iyengar S, Katon W . A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry. 2010; 67(10):1012-24. PMC: 3025772. DOI: 10.1001/archgenpsychiatry.2010.111. View

Moosavi A, Motevalizadeh Ardekani A . Role of Epigenetics in Biology and Human Diseases. Iran Biomed J. 2016; 20(5):246-58. PMC: 5075137. DOI: 10.22045/ibj.2016.01. View

Kiyonaka S, Nakajima H, Takada Y, Hida Y, Yoshioka T, Hagiwara A . Physical and functional interaction of the active zone protein CAST/ERC2 and the β-subunit of the voltage-dependent Ca(2+) channel. J Biochem. 2012; 152(2):149-59. DOI: 10.1093/jb/mvs054. View

Sosnowski D, Booth C, York T, Amstadter A, Kliewer W . Maternal prenatal stress and infant DNA methylation: A systematic review. Dev Psychobiol. 2018; 60(2):127-139. DOI: 10.1002/dev.21604. View

10.

Bleker L, de Rooij S, Roseboom T . Programming Effects of Prenatal Stress on Neurodevelopment-The Pitfall of Introducing a Self-Fulfilling Prophecy. Int J Environ Res Public Health. 2019; 16(13). PMC: 6651796. DOI: 10.3390/ijerph16132301. View

11.

Teschendorff A, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D . A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 2012; 29(2):189-96. PMC: 3546795. DOI: 10.1093/bioinformatics/bts680. View

12.

Cheung K, Kim C, Zhou M . The Functions of BET Proteins in Gene Transcription of Biology and Diseases. Front Mol Biosci. 2021; 8:728777. PMC: 8446420. DOI: 10.3389/fmolb.2021.728777. View

13.

Sharma R, Frasch M, Zelgert C, Zimmermann P, Fabre B, Wilson R . Maternal-fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study. Clin Epigenetics. 2022; 14(1):87. PMC: 9281078. DOI: 10.1186/s13148-022-01310-x. View

14.

Van den Bergh B, Mulder E, Mennes M, Glover V . Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev. 2005; 29(2):237-58. DOI: 10.1016/j.neubiorev.2004.10.007. View

15.

Lilliecreutz C, Laren J, Sydsjo G, Josefsson A . Effect of maternal stress during pregnancy on the risk for preterm birth. BMC Pregnancy Childbirth. 2016; 16:5. PMC: 4714539. DOI: 10.1186/s12884-015-0775-x. View

16.

Liu Y, Murphy S, Murtha A, Fuemmeler B, Schildkraut J, Huang Z . Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements. Epigenetics. 2012; 7(7):735-46. PMC: 3414394. DOI: 10.4161/epi.20734. View

17.

Beck C . The effects of postpartum depression on child development: a meta-analysis. Arch Psychiatr Nurs. 1998; 12(1):12-20. DOI: 10.1016/s0883-9417(98)80004-6. View

18.

Robles-Matos N, Artis T, Simmons R, Bartolomei M . Environmental Exposure to Endocrine Disrupting Chemicals Influences Genomic Imprinting, Growth, and Metabolism. Genes (Basel). 2021; 12(8). PMC: 8393470. DOI: 10.3390/genes12081153. View

19.

Pope C, Mazmanian D . Breastfeeding and Postpartum Depression: An Overview and Methodological Recommendations for Future Research. Depress Res Treat. 2016; 2016:4765310. PMC: 4842365. DOI: 10.1155/2016/4765310. View

20.

Feng L, Huang Y, Zhang W, Li L . LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer. J Ovarian Res. 2021; 14(1):67. PMC: 8126133. DOI: 10.1186/s13048-021-00807-y. View