The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder
Abstract Background Stressful life events influence the course of affective disorders, however, the mechanisms by which they bring about phenotypic change are not entirely known. Methods We explored the role of DNA methylation in response to recent stressful life events in a cohort of bipolar patien...
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SpringerOpen
2020-02-01
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Series: | International Journal of Bipolar Disorders |
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Online Access: | https://doi.org/10.1186/s40345-019-0176-6 |
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language |
English |
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DOAJ |
author |
Ashley L. Comes Darina Czamara Kristina Adorjan Heike Anderson-Schmidt Till F. M. Andlauer Monika Budde Katrin Gade Maria Hake Janos L. Kalman Sergi Papiol Daniela Reich-Erkelenz Farah Klöhn-Saghatolislam Sabrina K. Schaupp Eva C. Schulte Fanny Senner Georg Juckel Max Schmauß Jörg Zimmermann Jens Reimer Eva Reininghaus Ion-George Anghelescu Carsten Konrad Andreas Thiel Christian Figge Martin von Hagen Manfred Koller Detlef E. Dietrich Sebastian Stierl Harald Scherk Stephanie H. Witt Sugirthan Sivalingam Franziska Degenhardt Andreas J. Forstner Marcella Rietschel Markus M. Nöthen Jens Wiltfang Peter Falkai Thomas G. Schulze Urs Heilbronner |
spellingShingle |
Ashley L. Comes Darina Czamara Kristina Adorjan Heike Anderson-Schmidt Till F. M. Andlauer Monika Budde Katrin Gade Maria Hake Janos L. Kalman Sergi Papiol Daniela Reich-Erkelenz Farah Klöhn-Saghatolislam Sabrina K. Schaupp Eva C. Schulte Fanny Senner Georg Juckel Max Schmauß Jörg Zimmermann Jens Reimer Eva Reininghaus Ion-George Anghelescu Carsten Konrad Andreas Thiel Christian Figge Martin von Hagen Manfred Koller Detlef E. Dietrich Sebastian Stierl Harald Scherk Stephanie H. Witt Sugirthan Sivalingam Franziska Degenhardt Andreas J. Forstner Marcella Rietschel Markus M. Nöthen Jens Wiltfang Peter Falkai Thomas G. Schulze Urs Heilbronner The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder International Journal of Bipolar Disorders DNA methylation Bipolar disorder Stressful life events Longitudinal Epigenomics Epigenetic aging |
author_facet |
Ashley L. Comes Darina Czamara Kristina Adorjan Heike Anderson-Schmidt Till F. M. Andlauer Monika Budde Katrin Gade Maria Hake Janos L. Kalman Sergi Papiol Daniela Reich-Erkelenz Farah Klöhn-Saghatolislam Sabrina K. Schaupp Eva C. Schulte Fanny Senner Georg Juckel Max Schmauß Jörg Zimmermann Jens Reimer Eva Reininghaus Ion-George Anghelescu Carsten Konrad Andreas Thiel Christian Figge Martin von Hagen Manfred Koller Detlef E. Dietrich Sebastian Stierl Harald Scherk Stephanie H. Witt Sugirthan Sivalingam Franziska Degenhardt Andreas J. Forstner Marcella Rietschel Markus M. Nöthen Jens Wiltfang Peter Falkai Thomas G. Schulze Urs Heilbronner |
author_sort |
Ashley L. Comes |
title |
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder |
title_short |
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder |
title_full |
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder |
title_fullStr |
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder |
title_full_unstemmed |
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder |
title_sort |
role of environmental stress and dna methylation in the longitudinal course of bipolar disorder |
publisher |
SpringerOpen |
series |
International Journal of Bipolar Disorders |
issn |
2194-7511 |
publishDate |
2020-02-01 |
description |
Abstract Background Stressful life events influence the course of affective disorders, however, the mechanisms by which they bring about phenotypic change are not entirely known. Methods We explored the role of DNA methylation in response to recent stressful life events in a cohort of bipolar patients from the longitudinal PsyCourse study (n = 96). Peripheral blood DNA methylomes were profiled at two time points for over 850,000 methylation sites. The association between impact ratings of stressful life events and DNA methylation was assessed, first by interrogating methylation sites in the vicinity of candidate genes previously implicated in the stress response and, second, by conducting an exploratory epigenome-wide association analysis. Third, the association between epigenetic aging and change in stress and symptom measures over time was investigated. Results Investigation of methylation signatures over time revealed just over half of the CpG sites tested had an absolute difference in methylation of at least 1% over a 1-year period. Although not a single CpG site withstood correction for multiple testing, methylation at one site (cg15212455) was suggestively associated with stressful life events (p < 1.0 × 10−5). Epigenetic aging over a 1-year period was not associated with changes in stress or symptom measures. Conclusions To the best of our knowledge, our study is the first to investigate epigenome-wide methylation across time in bipolar patients and in relation to recent, non-traumatic stressful life events. Limited and inconclusive evidence warrants future longitudinal investigations in larger samples of well-characterized bipolar patients to give a complete picture regarding the role of DNA methylation in the course of bipolar disorder. |
topic |
DNA methylation Bipolar disorder Stressful life events Longitudinal Epigenomics Epigenetic aging |
url |
https://doi.org/10.1186/s40345-019-0176-6 |
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doaj-d9a20649518a4c5f8f2c241edc22b7812021-02-14T12:19:55ZengSpringerOpenInternational Journal of Bipolar Disorders2194-75112020-02-018111210.1186/s40345-019-0176-6The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorderAshley L. Comes0Darina Czamara1Kristina Adorjan2Heike Anderson-Schmidt3Till F. M. Andlauer4Monika Budde5Katrin Gade6Maria Hake7Janos L. Kalman8Sergi Papiol9Daniela Reich-Erkelenz10Farah Klöhn-Saghatolislam11Sabrina K. Schaupp12Eva C. Schulte13Fanny Senner14Georg Juckel15Max Schmauß16Jörg Zimmermann17Jens Reimer18Eva Reininghaus19Ion-George Anghelescu20Carsten Konrad21Andreas Thiel22Christian Figge23Martin von Hagen24Manfred Koller25Detlef E. Dietrich26Sebastian Stierl27Harald Scherk28Stephanie H. Witt29Sugirthan Sivalingam30Franziska Degenhardt31Andreas J. Forstner32Marcella Rietschel33Markus M. Nöthen34Jens Wiltfang35Peter Falkai36Thomas G. Schulze37Urs Heilbronner38Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichDepartment of Psychiatry and Psychotherapy, University Medical Center GöttingenInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichDepartment of Psychiatry, Ruhr University Bochum, LWL University HospitalDepartment of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, University of AugsburgPsychiatrieverbund Oldenburger Land gGmbH, Karl-Jaspers-KlinikDepartment of Psychiatry and Psychotherapy, University Medical Center Hamburg-EppendorfDepartment of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of GrazDepartment of Psychiatry, Dr. Frontheim-Mental HealthDepartment of Psychiatry and Psychotherapy, Agaplesion DiakonieklinikumDepartment of Psychiatry and Psychotherapy, Agaplesion DiakonieklinikumKarl-Jaspers Clinic, European Medical School Oldenburg-GroningenClinic for Psychiatry and Psychotherapy, Clinical Center Werra-MeißnerAsklepios Specialized HospitalAMEOS Clinical Center HildesheimPsychiatric Hospital LüneburgAMEOS Clinical Center OsnabrückDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of HeidelbergInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnDepartment of Psychiatry and Psychotherapy, University Medical Center GöttingenDepartment of Psychiatry and Psychotherapy, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichInstitute of Psychiatric Phenomics and Genomics, University Hospital, LMU MunichAbstract Background Stressful life events influence the course of affective disorders, however, the mechanisms by which they bring about phenotypic change are not entirely known. Methods We explored the role of DNA methylation in response to recent stressful life events in a cohort of bipolar patients from the longitudinal PsyCourse study (n = 96). Peripheral blood DNA methylomes were profiled at two time points for over 850,000 methylation sites. The association between impact ratings of stressful life events and DNA methylation was assessed, first by interrogating methylation sites in the vicinity of candidate genes previously implicated in the stress response and, second, by conducting an exploratory epigenome-wide association analysis. Third, the association between epigenetic aging and change in stress and symptom measures over time was investigated. Results Investigation of methylation signatures over time revealed just over half of the CpG sites tested had an absolute difference in methylation of at least 1% over a 1-year period. Although not a single CpG site withstood correction for multiple testing, methylation at one site (cg15212455) was suggestively associated with stressful life events (p < 1.0 × 10−5). Epigenetic aging over a 1-year period was not associated with changes in stress or symptom measures. Conclusions To the best of our knowledge, our study is the first to investigate epigenome-wide methylation across time in bipolar patients and in relation to recent, non-traumatic stressful life events. Limited and inconclusive evidence warrants future longitudinal investigations in larger samples of well-characterized bipolar patients to give a complete picture regarding the role of DNA methylation in the course of bipolar disorder.https://doi.org/10.1186/s40345-019-0176-6DNA methylationBipolar disorderStressful life eventsLongitudinalEpigenomicsEpigenetic aging |