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

T. Hompes, B. Izzi, E. Gellens, M. Morreels, S. Fieuws, A. Pexsters, G. Schops, M. Dom, R. van Bree, K. Freson, J. Verhaeghe, B. Spitz, K. Demyttenaere, V. Glover, B.R.H. Van den Bergh, K. Allegaert, S. Claes

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background
The methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene.
Methods
We examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells.
Results
Univariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8% (p = 0.023) during T1.
Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9% and PVE:9.0%; Fear of delivery T2: PVE:8.0%, Fear of integrity T2: PVE:6.0% and STAI T2: PVE:5.9%) – (F12.13: PC PRAQ T1: PVE:6.9%, fear of integrity T2: PVE:6.0% and fear of delivery T2: PVE:8.0%)] and cortisol (F38.39: PVE:8.9%) in T2.
Conclusion
These data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.
Keywords: Prenatal maternal emotional wellbeing, Maternal HPA axis, Methylation state NR3C1, Maternal anxiety
Original languageEnglish
Pages (from-to)880-891
JournalJournal of Psychiatric Research
Volume47
Issue number7
DOIs
Publication statusPublished - 2013

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DNA Methylation
Fetal Blood
Mothers
Nerve Growth Factor
Newborn Infant
DNA

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Hompes, T. ; Izzi, B. ; Gellens, E. ; Morreels, M. ; Fieuws, S. ; Pexsters, A. ; Schops, G. ; Dom, M. ; van Bree, R. ; Freson, K. ; Verhaeghe, J. ; Spitz, B. ; Demyttenaere, K. ; Glover, V. ; Van den Bergh, B.R.H. ; Allegaert, K. ; Claes, S. / 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. In: Journal of Psychiatric Research. 2013 ; Vol. 47, No. 7. pp. 880-891.
@article{4192d8af8d19447fb761cf366d2993e4,
title = "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",
abstract = "BackgroundThe methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene.MethodsWe examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells.ResultsUnivariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8{\%} (p = 0.023) during T1.Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9{\%} and PVE:9.0{\%}; Fear of delivery T2: PVE:8.0{\%}, Fear of integrity T2: PVE:6.0{\%} and STAI T2: PVE:5.9{\%}) – (F12.13: PC PRAQ T1: PVE:6.9{\%}, fear of integrity T2: PVE:6.0{\%} and fear of delivery T2: PVE:8.0{\%})] and cortisol (F38.39: PVE:8.9{\%}) in T2.ConclusionThese data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.Keywords: Prenatal maternal emotional wellbeing, Maternal HPA axis, Methylation state NR3C1, Maternal anxiety",
author = "T. Hompes and B. Izzi and E. Gellens and M. Morreels and S. Fieuws and A. Pexsters and G. Schops and M. Dom and {van Bree}, R. and K. Freson and J. Verhaeghe and B. Spitz and K. Demyttenaere and V. Glover and {Van den Bergh}, B.R.H. and K. Allegaert and S. Claes",
year = "2013",
doi = "10.1016/j.jpsychires.2013.03.009",
language = "English",
volume = "47",
pages = "880--891",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier Limited",
number = "7",

}

Hompes, T, Izzi, B, Gellens, E, Morreels, M, Fieuws, S, Pexsters, A, Schops, G, Dom, M, van Bree, R, Freson, K, Verhaeghe, J, Spitz, B, Demyttenaere, K, Glover, V, Van den Bergh, BRH, Allegaert, K & Claes, S 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 Research, vol. 47, no. 7, pp. 880-891. https://doi.org/10.1016/j.jpsychires.2013.03.009

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. / Hompes, T.; Izzi, B.; Gellens, E.; Morreels, M.; Fieuws, S.; Pexsters, A.; Schops, G.; Dom, M.; van Bree, R.; Freson, K.; Verhaeghe, J.; Spitz, B.; Demyttenaere, K.; Glover, V.; Van den Bergh, B.R.H.; Allegaert, K.; Claes, S.

In: Journal of Psychiatric Research, Vol. 47, No. 7, 2013, p. 880-891.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - 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

AU - Hompes, T.

AU - Izzi, B.

AU - Gellens, E.

AU - Morreels, M.

AU - Fieuws, S.

AU - Pexsters, A.

AU - Schops, G.

AU - Dom, M.

AU - van Bree, R.

AU - Freson, K.

AU - Verhaeghe, J.

AU - Spitz, B.

AU - Demyttenaere, K.

AU - Glover, V.

AU - Van den Bergh, B.R.H.

AU - Allegaert, K.

AU - Claes, S.

PY - 2013

Y1 - 2013

N2 - BackgroundThe methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene.MethodsWe examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells.ResultsUnivariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8% (p = 0.023) during T1.Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9% and PVE:9.0%; Fear of delivery T2: PVE:8.0%, Fear of integrity T2: PVE:6.0% and STAI T2: PVE:5.9%) – (F12.13: PC PRAQ T1: PVE:6.9%, fear of integrity T2: PVE:6.0% and fear of delivery T2: PVE:8.0%)] and cortisol (F38.39: PVE:8.9%) in T2.ConclusionThese data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.Keywords: Prenatal maternal emotional wellbeing, Maternal HPA axis, Methylation state NR3C1, Maternal anxiety

AB - BackgroundThe methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene.MethodsWe examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells.ResultsUnivariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8% (p = 0.023) during T1.Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9% and PVE:9.0%; Fear of delivery T2: PVE:8.0%, Fear of integrity T2: PVE:6.0% and STAI T2: PVE:5.9%) – (F12.13: PC PRAQ T1: PVE:6.9%, fear of integrity T2: PVE:6.0% and fear of delivery T2: PVE:8.0%)] and cortisol (F38.39: PVE:8.9%) in T2.ConclusionThese data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.Keywords: Prenatal maternal emotional wellbeing, Maternal HPA axis, Methylation state NR3C1, Maternal anxiety

U2 - 10.1016/j.jpsychires.2013.03.009

DO - 10.1016/j.jpsychires.2013.03.009

M3 - Article

VL - 47

SP - 880

EP - 891

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

SN - 0022-3956

IS - 7

ER -