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Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates Gurnot, Cécile; Martin-Subero, Ignacio; Mah, Sarah M.; Weikum, Whitney Marie; Goodman, Sarah Jessica; Brain, Ursula; Werker, Janet Feldman, 1951-; Kobor, Michael S. (Geneticist); Esteller, Manel; Oberlander, Tim F.; et al.

Abstract

Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these two exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status—both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05)—was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 methylation status, which, in turn, appeared to be associated with birth weight.

Item Metadata

Title
Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates
Creator
Gurnot, Cécile; Martin-Subero, Ignacio; Mah, Sarah M.; Weikum, Whitney Marie; Goodman, Sarah Jessica; Brain, Ursula; Werker, Janet Feldman, 1951-; Kobor, Michael S. (Geneticist); Esteller, Manel; Oberlander, Tim F.; Hensch, Takao K.
Contributor
Child and Family Research Institute; University of British Columbia. Centre for Molecular Medicine and Therapeutics; Human Early Learning Partnership (Vancouver, B.C.)
Publisher
Taylor & Francis
Date Issued
2015-04-27
Description
Some but not all neonates are affected by prenatal exposure to serotonin reuptake inhibitor antidepressants (SRI) and maternal mood disturbances. Distinguishing the impact of these two exposures is challenging and raises critical questions about whether pharmacological, genetic, or epigenetic factors can explain the spectrum of reported outcomes. Using unbiased DNA methylation array measurements followed by a detailed candidate gene approach, we examined whether prenatal SRI exposure was associated with neonatal DNA methylation changes and whether such changes were associated with differences in birth outcomes. Prenatal SRI exposure was first associated with increased DNA methylation status primarily at CYP2E1(βNon-exposed = 0.06, βSRI-exposed = 0.30, FDR = 0); however, this finding could not be distinguished from the potential impact of prenatal maternal depressed mood. Then, using pyrosequencing of CYP2E1 regulatory regions in an expanded cohort, higher DNA methylation status—both the mean across 16 CpG sites (P < 0.01) and at each specific CpG site (P < 0.05)—was associated with exposure to lower 3rd trimester maternal depressed mood symptoms only in the SRI-exposed neonates, indicating a maternal mood x SRI exposure interaction. In addition, higher DNA methylation levels at CpG2 (P = 0.04), CpG9 (P = 0.04) and CpG10 (P = 0.02), in the interrogated CYP2E1 region, were associated with increased birth weight independently of prenatal maternal mood, SRI drug exposure, or gestational age at birth. Prenatal SRI antidepressant exposure and maternal depressed mood were associated with altered neonatal CYP2E1 methylation status, which, in turn, appeared to be associated with birth weight.
Subject
Serotonin reuptake inhibitor (SRI) antidepressants; Depression; Pregnancy; Neonatal health; CYP2E1
Genre
Article; Postprint
Type
Text
Language
eng
Date Available
2019-12-19
Provider
Vancouver : University of British Columbia Library
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
DOI
10.14288/1.0387233
URI
http://hdl.handle.net/2429/72881
Affiliation
Arts, Faculty of; Medicine, Faculty of; Other UBC; Non UBC; Medical Genetics, Department of; Pediatrics, Department of; Psychology, Department of
Citation
Gurnot, C., Martin-Subero, J., Mah, J., Weikum, W., Goodman, S., Brain, U., Werker, J.F., Kobor, M., Esteller, M., Oberlander, T., & Hensch, T.K. (2015). Prenatal antidepressant exposure associated with CYP2E1 DNA methylation change in neonates. Epigenetics, 10(5), 361-372.
Publisher DOI
10.1080/15592294.2015.1026031
Peer Review Status
Reviewed
Scholarly Level
Faculty; Graduate
Rights URI
http://creativecommons.org/licenses/by-nc-nd/4.0/
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Attribution-NonCommercial-NoDerivatives 4.0 International