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Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy
Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood. In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placent...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803674/ https://www.ncbi.nlm.nih.gov/pubmed/36585414 http://dx.doi.org/10.1038/s41598-022-26071-8 |
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author | Inkster, Amy M. Konwar, Chaini Peñaherrera, Maria S. Brain, Ursula Khan, Almas Price, E. Magda Schuetz, Johanna M. Portales-Casamar, Élodie Burt, Amber Marsit, Carmen J. Vaillancourt, Cathy Oberlander, Tim F. Robinson, Wendy P. |
author_facet | Inkster, Amy M. Konwar, Chaini Peñaherrera, Maria S. Brain, Ursula Khan, Almas Price, E. Magda Schuetz, Johanna M. Portales-Casamar, Élodie Burt, Amber Marsit, Carmen J. Vaillancourt, Cathy Oberlander, Tim F. Robinson, Wendy P. |
author_sort | Inkster, Amy M. |
collection | PubMed |
description | Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood. In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placenta, an epigenetic mark that is established during development and is associated with gene expression. Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip; clinical assessments of maternal mood and SSRI treatment records were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression was defined using a mean maternal Hamilton Depression score > 8 to indicate symptomatic depressed mood (“maternally-depressed”), and we further classified cases into SSRI-exposed, maternally-depressed (n = 14); SSRI-exposed, not maternally-depressed (n = 6); SSRI non-exposed, maternally-depressed (n = 20); and SSRI non-exposed, not maternally-depressed (n = 24). For replication, Illumina 450K DNAme profiles were obtained from 34 additional cases from an independent cohort (n = 17 SSRI-exposed, n = 17 SSRI non-exposed). No CpGs were differentially methylated at FDR < 0.05 comparing SSRI-exposed to non-exposed placentas, in a model adjusted for mean maternal Hamilton Depression score, or in a model restricted to maternally-depressed cases with and without SSRI exposure. However, at a relaxed threshold of FDR < 0.25, five CpGs were differentially methylated (|Δβ| > 0.03) by SSRI exposure status. Four were covered by the replication cohort measured by the 450K array, but none replicated. No CpGs were differentially methylated (FDR < 0.25) comparing maternally depressed to not depressed cases. In sex-stratified analyses for SSRI-exposed versus non-exposed cases (females n = 31; males n = 33), three additional CpGs in females, but none in males, were differentially methylated at the relaxed FDR < 0.25 cut-off. We did not observe large-scale alterations of DNAme in placentas exposed to maternal SSRI treatment, as compared to placentas with no SSRI exposure. We also found no evidence for altered DNAme in maternal depression-exposed versus depression non-exposed placentas. This novel work in a prospectively-recruited cohort with clinician-ascertained SSRI exposure and mood assessments would benefit from future replication. |
format | Online Article Text |
id | pubmed-9803674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98036742023-01-01 Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy Inkster, Amy M. Konwar, Chaini Peñaherrera, Maria S. Brain, Ursula Khan, Almas Price, E. Magda Schuetz, Johanna M. Portales-Casamar, Élodie Burt, Amber Marsit, Carmen J. Vaillancourt, Cathy Oberlander, Tim F. Robinson, Wendy P. Sci Rep Article Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood. In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placenta, an epigenetic mark that is established during development and is associated with gene expression. Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip; clinical assessments of maternal mood and SSRI treatment records were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression was defined using a mean maternal Hamilton Depression score > 8 to indicate symptomatic depressed mood (“maternally-depressed”), and we further classified cases into SSRI-exposed, maternally-depressed (n = 14); SSRI-exposed, not maternally-depressed (n = 6); SSRI non-exposed, maternally-depressed (n = 20); and SSRI non-exposed, not maternally-depressed (n = 24). For replication, Illumina 450K DNAme profiles were obtained from 34 additional cases from an independent cohort (n = 17 SSRI-exposed, n = 17 SSRI non-exposed). No CpGs were differentially methylated at FDR < 0.05 comparing SSRI-exposed to non-exposed placentas, in a model adjusted for mean maternal Hamilton Depression score, or in a model restricted to maternally-depressed cases with and without SSRI exposure. However, at a relaxed threshold of FDR < 0.25, five CpGs were differentially methylated (|Δβ| > 0.03) by SSRI exposure status. Four were covered by the replication cohort measured by the 450K array, but none replicated. No CpGs were differentially methylated (FDR < 0.25) comparing maternally depressed to not depressed cases. In sex-stratified analyses for SSRI-exposed versus non-exposed cases (females n = 31; males n = 33), three additional CpGs in females, but none in males, were differentially methylated at the relaxed FDR < 0.25 cut-off. We did not observe large-scale alterations of DNAme in placentas exposed to maternal SSRI treatment, as compared to placentas with no SSRI exposure. We also found no evidence for altered DNAme in maternal depression-exposed versus depression non-exposed placentas. This novel work in a prospectively-recruited cohort with clinician-ascertained SSRI exposure and mood assessments would benefit from future replication. Nature Publishing Group UK 2022-12-30 /pmc/articles/PMC9803674/ /pubmed/36585414 http://dx.doi.org/10.1038/s41598-022-26071-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Inkster, Amy M. Konwar, Chaini Peñaherrera, Maria S. Brain, Ursula Khan, Almas Price, E. Magda Schuetz, Johanna M. Portales-Casamar, Élodie Burt, Amber Marsit, Carmen J. Vaillancourt, Cathy Oberlander, Tim F. Robinson, Wendy P. Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy |
title | Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy |
title_full | Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy |
title_fullStr | Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy |
title_full_unstemmed | Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy |
title_short | Profiling placental DNA methylation associated with maternal SSRI treatment during pregnancy |
title_sort | profiling placental dna methylation associated with maternal ssri treatment during pregnancy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803674/ https://www.ncbi.nlm.nih.gov/pubmed/36585414 http://dx.doi.org/10.1038/s41598-022-26071-8 |
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