Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-03T01:03:59.777Z Has data issue: false hasContentIssue false
  • English
  • Français

Maternal mental well-being during pregnancy and glucocorticoid receptor gene promoter methylation in the neonate

Published online by Cambridge University Press:  04 April 2016

Toby Mansell ,
Peter Vuillermin ,
Anne-Louise Ponsonby ,
Fiona Collier ,
Richard Saffery ,
Joanne Ryan  and
Barwon Infant Study Investigator Team
Toby Mansell
Affiliation:
Royal Children's Hospital University of Melbourne
Peter Vuillermin
Affiliation:
Royal Children's Hospital University of Melbourne Barwon Health Deakin University
Anne-Louise Ponsonby
Affiliation:
Royal Children's Hospital University of Melbourne
Fiona Collier
Affiliation:
Barwon Health Deakin University
Richard Saffery
Affiliation:
Royal Children's Hospital University of Melbourne
Joanne Ryan*
Affiliation:
Royal Children's Hospital University of Melbourne Hopital La Colombiere Universite Montpellier
*
Address correspondence and reprint requests to: Joanne Ryan, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia; E-mail: [email protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

Maternal mental health during pregnancy has been linked to health outcomes in progeny. Mounting evidence implicates fetal “programming” in this process, possibly via epigenetic disruption. Maternal mental health has been associated with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) in the neonate; however, most studies have been small (n < 100) and have failed to control for multiple testing in the statistical analysis. The Barwon Infant Study is a population-derived birth cohort with antenatal recruitment. Maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale and psychological distress using the Perceived Stress Scale. NR3C1 cord blood methylation levels were determined using Sequenom MassArray for 481 participants. Maternal psychological distress and anxiety were associated with a small increase in neonate NR3C1 methylation at specific CpG sites, thus replicating some previous findings. However, associations were only nominally significant and did not remain after correction for the number of CpG sites and exposures investigated. As the largest study to explore the relationship between maternal well-being and offspring NR3C1 cord blood methylation, our results highlight the need for caution when interpreting previous findings in this area. Future studies must ensure they are adequately powered to detect the likely small effect sizes while controlling for multiple testing.

Type
Regular Articles
Information
Development and Psychopathology , Volume 28 , Special Issue 4pt2: Epigenetics: Development, Psychopathology, Resilience, and Preventive Intervention , November 2016 , pp. 1421 - 1430
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bergink, V., Kooistra, L., Lambregtse-van den Berg, M. P., Wijnen, H., Bunevicius, R., van Baar, A., & Pop, V. (2011). Validation of the Edinburgh Depression Scale during pregnancy. Journal of Psychosomatic Research, 70, 385–389.CrossRefGoogle ScholarPubMed
Beydoun, H., & Saftlas, A. F. (2008). Physical and mental health outcomes of prenatal maternal stress in human and animal studies: A review of recent evidence. Paediatric and Perinatal Epidemiology, 22, 438–466 CrossRefGoogle ScholarPubMed
Braithwaite, E. C., Kundakovic, M., Ramchandani, P. G., Murphy, S. E., & Champagne, F. A. (2015). Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics. Advance online publication.CrossRefGoogle ScholarPubMed
Bureau, J. F., Easterbrooks, M. A., & Lyons-Ruth, K. (2009). Maternal depressive symptoms in infancy: Unique contribution to children's depressive symptoms in childhood and adolescence? Development and Psychopathology, 21, 519–537.CrossRefGoogle ScholarPubMed
Button, K. S., Ioannidis, J. P., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S., et al. (2013). Power failure: Why small sample size undermines the reliability of neuroscience. Nature Reviews Neuroscience, 14, 365–376.CrossRefGoogle ScholarPubMed
Capra, L., Tezza, G., Mazzei, F., & Boner, A. L. (2013). The origins of health and disease: The influence of maternal diseases and lifestyle during gestation. Italian Journal of Pediatrics, 39, 7.CrossRefGoogle ScholarPubMed
Cohen, S., Kamarck, T., & Mermelstein, R. (1983). A global measure of perceived stress. Journal of Health and Social Behavior, 24, 385–396.CrossRefGoogle ScholarPubMed
Conradt, E., Lester, B., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013). The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics, 8, 1321.CrossRefGoogle ScholarPubMed
Cox, J. L., Holden, J. M., & Sagovsky, R. (1987). Detection of postnatal depression: Development of the 10-item Edinburgh Postnatal Depression Scale. British Journal of Psychiatry, 150, 782–786.CrossRefGoogle ScholarPubMed
Ehrich, M., Nelson, M. R., Stanssens, P., Zabeau, M., Liloglou, T., Xinarianos, G., et al. (2005). Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proceedings of the National Academy of Sciences, 102, 15785–15790.CrossRefGoogle ScholarPubMed
Entringer, S., Kumsta, R., Hellhammer, D. H., Wadhwa, P. D., & Wust, S. (2009). Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults. Hormones and Behavior, 55, 292–298.CrossRefGoogle ScholarPubMed
Geuze, E. E. J. D. (2005). MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Molecular Psychiatry, 10, 160–184.CrossRefGoogle ScholarPubMed
Gluckman, P. D., & Hanson, M. A. (2004). Developmental origins of disease paradigm: A mechanistic and evolutionary perspective. Pediatric Research, 56, 311–317.CrossRefGoogle ScholarPubMed
Gotz, A. A., & Stefanski, V. (2007). Psychosocial maternal stress during pregnancy affects serum corticosterone, blood immune parameters and anxiety behavior in adult male rat offspring. Physiology & Behavior, 90, 108–115.CrossRefGoogle ScholarPubMed
Grigoriadis, S., VonderPorten, E. H., Mamisashvili, L., Tomlinson, G., Dennis, C. L., Koren, G., et al. (2013). The impact of maternal depression during pregnancy on perinatal outcomes: A systematic review and meta-analysis. Journal of Clinical Psychiatry, 74, e321–e341.CrossRefGoogle ScholarPubMed
Grote, N. K., Bridge, J. A., Gavin, A. R., Melville, J. L., Iyengar, S., & Katon, W. J. (2010). A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Archives of General Psychiatry, 67, 1012–1024.CrossRefGoogle ScholarPubMed
Hedegaard, M., Henriksen, T. B., Secher, N. J., Hatch, M. C., & Sabroe, S. (1996). Do stressful life events affect duration of gestation and risk of preterm delivery? Epidemiology, 7, 339–345.CrossRefGoogle ScholarPubMed
Herbert, J. (2013). Cortisol and depression: Three questions for psychiatry. Psychological Medicine, 43, 449–469.CrossRefGoogle ScholarPubMed
Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., et al. (2013). Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Reserch, 47, 880–891.CrossRefGoogle ScholarPubMed
Igosheva, N., Taylor, P. D., Poston, L., & Glover, V. (2007). Prenatal stress in the rat results in increased blood pressure responsiveness to stress and enhanced arterial reactivity to neuropeptide Y in adulthood. Journal of Physiology, 582, 665–674.CrossRefGoogle ScholarPubMed
Jacobson, L. (2014). Hypothalamic-pituitary-adrenocortical axis: Neuropsychiatric aspects. Comprehensive Physiology, 4, 715–738.CrossRefGoogle ScholarPubMed
Kapoor, A., Dunn, E., Kostaki, A., Andrews, M. H., & Matthews, S. G. (2006). Fetal programming of hypothalamo-pituitary-adrenal function: Prenatal stress and glucocorticoids. Journal of Physiology, 572, 31–44.CrossRefGoogle ScholarPubMed
Martino, D., Loke, Y. J., Gordon, L., Ollikainen, M., Cruickshank, M. N., Saffery, R., et al. (2013). Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance. Genome Biology, 14, R42.CrossRefGoogle ScholarPubMed
Matthey, S. (2008). Using the Edinburgh Postnatal Depression Scale to screen for anxiety disorders. Depression and Anxiety, 25, 926–931.CrossRefGoogle ScholarPubMed
Matthey, S., Fisher, J., & Rowe, H. (2013). Using the Edinburgh Postnatal Depression Scale to screen for anxiety disorders: Conceptual and methodological considerations. Journal of Affective Disorders, 146, 224–230.CrossRefGoogle ScholarPubMed
Mulligan, C. J., D'Errico, N. C., Stees, J., & Hughes, D. A. (2012). Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics, 7, 853–857.CrossRefGoogle ScholarPubMed
Mund, M., Louwen, F., Klingelhoefer, D., & Gerber, A. (2013). Smoking and pregnancy—A review on the first major environmental risk factor of the unborn. International Journal of Environmental Research and Public Health, 10, 6485–6499.CrossRefGoogle ScholarPubMed
Nemoda, Z., Massart, R., Suderman, M., Hallett, M., Li, T., Coote, M., et al. (2015). Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi. Translational Psychiatry, 5, e545.CrossRefGoogle ScholarPubMed
Non, A. L., Binder, A. M., Kubzansky, L. D., & Michels, K. B. (2014). Genome-wide DNA methylation in neonates exposed to maternal depression, anxiety, or SSRI medication during pregnancy. Epigenetics, 9, 964–972.CrossRefGoogle ScholarPubMed
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3, 97–106.CrossRefGoogle ScholarPubMed
Pariante, C. M., & Lightman, S. L. (2008). The HPA axis in major depression: Classical theories and new developments. Trends in Neurosciences, 31, 464–468.CrossRefGoogle ScholarPubMed
Potter, C., McKay, J., Groom, A., Ford, D., Coneyworth, L., Mathers, J. C., et al. (2013). Influence of DNMT genotype on global and site specific DNA methylation patterns in neonates and pregnant women. PLOS ONE, 8, e76506.CrossRefGoogle ScholarPubMed
Rallis, S., Skouteris, H., McCabe, M., & Milgrom, J. (2014). A prospective examination of depression, anxiety and stress throughout pregnancy. Women and Birth, 27, e36–e42.CrossRefGoogle ScholarPubMed
Rodriguez, A. G. (2005). Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? Journal of Child Psychology & Psychiatry, 46, 246–254.CrossRefGoogle ScholarPubMed
Schroeder, J. W., Smith, A. K., Brennan, P. A., Conneely, K. N., Kilaru, V., Knight, B. T., et al. (2012). DNA methylation in neonates born to women receiving psychiatric care. Epigenetics, 7, 409–414.CrossRefGoogle ScholarPubMed
Sharp, H., Hill, J., Hellier, J., & Pickles, A. (2014). Maternal antenatal anxiety, postnatal stroking and emotional problems in children: Outcomes predicted from pre- and postnatal programming hypotheses. Psychological Medicine. Advance online publication.Google ScholarPubMed
Slykerman, R. F., Thompson, J., Waldie, K., Murphy, R., Wall, C., & Mitchell, E. A. (2014). Maternal stress during pregnancy is associated with moderate to severe depression in 11-year-old children. Acta Paediatrica. Advance online publication.Google ScholarPubMed
Swalm, D., Brooks, J., Doherty, D., Nathan, E., & Jacques, A. (2010). Using the Edinburgh Postnatal Depression Scale to screen for perinatal anxiety. Archives of Women's Mental Health, 13, 515–522.CrossRefGoogle ScholarPubMed
Teh, A. L., Pan, H., Chen, L., Ong, M. L., Dogra, S., Wong, J., et al. (2014). The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. Genome Research, 24, 1064–1074.CrossRefGoogle ScholarPubMed
Turecki, G., & Meaney, M. J. (2014). Effects of the social environment and stress on glucocorticoid receptor gene methylation: A systematic review. Biological Psychiatry. Advance online publication. doi:10.1016/j.biopsych.2014.11.022.Google ScholarPubMed
Vuillermin, P., Saffery, R., Allen, K. J., Carlin, J. B., Tang, M. L., Ranganathan, S., et al. (2015). Cohort profile: The Barwon Infant Study. International Journal of Epidemiology. Advance online publication.CrossRefGoogle ScholarPubMed
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 8, 847.CrossRefGoogle Scholar
Weinstock, M. (2001). Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Progress in Neurobiology, 65, 427–451.CrossRefGoogle ScholarPubMed
Supplementary material: File

Mansell supplementary material

Supplementary Figure

Download Mansell supplementary material(File)
File 38.3 KB