Abstract
Background: Recent work suggests that DNA methylation can be used as a proxy of fetal glucocorticoid exposure (MPS-GC), showing associations with maternal psychopathology during pregnancy. However, it is unknown whether the MPS-GC may act as a marker for broader prenatal stress and whether it partially mediates associations of prenatal stress with child internalizing and externalizing symptoms. Methods: Using harmonized data from three prospective birth cohorts (Npooled = 6086), we examined whether a cumulative measure of prenatal stress, and its individual stress domains, associate with the MPS-GC in cord blood at birth. Next, we examined (i) whether the MPS-GC at birth associates with child psychiatric symptoms, (ii) whether this association is moderated by postnatal stress, and (iii) whether the effect of prenatal stress on child psychiatric symptoms is partially mediated by the MPS-GC at birth. Results: Our meta-analysis revealed no significant associations between the MPS-GC at birth and prenatal stress or the individual stress domains. Moreover, the MPS-GC did not significantly associate with later child internalizing or externalizing symptoms, and there were no moderating effects of postnatal stress. Additionally, while prenatal stress significantly associated with child psychiatric symptoms, we found no partial mediation via the MPS-GC at birth. Conclusions: We did not find support that the MPS-GC in cord blood reliably proxies prenatal stress, associates with child psychiatric risk, or partially mediates the associations between prenatal stress and psychiatric risk.
| Original language | English |
|---|---|
| Article number | 107388 |
| Journal | Psychoneuroendocrinology |
| Volume | 175 |
| Early online date | 12 Feb 2025 |
| DOIs | |
| Publication status | E-pub ahead of print - 12 Feb 2025 |
Acknowledgements
The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The generation and management of the Illumina 450 K methylation array data (EWAS data) for the Generation R Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, The Netherlands. We thank Mr Michael Verbiest, Ms Mila Jhamai, Ms Sarah Higgins, Mr Marijn Verkerk and Dr Lisette Stolk for their help in creating the EWAS database. We thank Dr A. Teumer for his work on the quality control and normalization scripts.The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this on-going cohort study. We thank the Norwegian Institute of Public Health (NIPH) for generating high-quality genomic data. This research is part of the HARVEST collaboration, supported by the Research Council of Norway (#229624). We also thank the NORMENT Centre for providing genotype data, funded by the Research Council of Norway (#223273), South East Norway Versjon 7.0 3 Health Authorities and Stiftelsen Kristian Gerhard Jebsen. We further thank the Center for Diabetes Research, the University of Bergen for providing genotype data and performing quality control and imputation of the data funded by the ERC AdG project SELECTionPREDISPOSED, Stiftelsen Kristian Gerhard Jebsen, Trond Mohn Foundation, the Research Council of Norway, the Novo Nordisk Foundation, the University of Bergen, and the Western Norway Health Authorities.
Funding
The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. Additionally, This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme (EarlyCause [grant agreement No 848158, CAMC, JFF, EW, SD]), the European Union’s Horizon Europe Programme (STAGE [grant agreement no.101137146, CAMC, JFF]; FAMILY [grant agreement No 101057529, CAMC, AN]; HappyMums [grant agreement No 101057390, CAMC, IS]) and the European Research Council (TEMPO [grant agreement No 101039672, CAMC, AN). This research was conducted while CAMC was a Hevolution/AFAR New Investigator Awardee in Aging Biology and Geroscience Research. The work of NC was funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek [grant number 016.Vici.185.063]. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Esther Walton will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website. ARIES was specifically funded by the BBSRC (BBI025751/1 and BB/I025263/1). Supplementary funding to generate DNA methylation data which are (or will be) included in ARIES has been obtained from the MRC, ESRC, NIH and other sources. ARIES is maintained under the auspices of the MRC Integrative Epidemiology Unit at the University of Bristol (grant numbers MC_UU_12013/2, MC_UU_12013/8, and MC_UU_12013/9).
| Funders | Funder number |
|---|---|
| UK Research and Innovation Fund | 217065/Z/19/Z |
Keywords
- ALSPAC
- DNA methylation
- Externalizing
- Glucocorticoid
- Internalizing
- MoBa
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology
- Endocrine and Autonomic Systems
- Psychiatry and Mental health
- Biological Psychiatry
