International Journal of Bipolar Disorders (Feb 2020)
The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder
- 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
Affiliations
- Ashley L. Comes
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Darina Czamara
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry
- Kristina Adorjan
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Heike Anderson-Schmidt
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Till F. M. Andlauer
- Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry
- Monika Budde
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Katrin Gade
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen
- Maria Hake
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Janos L. Kalman
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Sergi Papiol
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Daniela Reich-Erkelenz
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Farah Klöhn-Saghatolislam
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Sabrina K. Schaupp
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Eva C. Schulte
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Fanny Senner
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Georg Juckel
- Department of Psychiatry, Ruhr University Bochum, LWL University Hospital
- Max Schmauß
- Department of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, University of Augsburg
- Jörg Zimmermann
- Psychiatrieverbund Oldenburger Land gGmbH, Karl-Jaspers-Klinik
- Jens Reimer
- Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf
- Eva Reininghaus
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz
- Ion-George Anghelescu
- Department of Psychiatry, Dr. Frontheim-Mental Health
- Carsten Konrad
- Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum
- Andreas Thiel
- Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum
- Christian Figge
- Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen
- Martin von Hagen
- Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner
- Manfred Koller
- Asklepios Specialized Hospital
- Detlef E. Dietrich
- AMEOS Clinical Center Hildesheim
- Sebastian Stierl
- Psychiatric Hospital Lüneburg
- Harald Scherk
- AMEOS Clinical Center Osnabrück
- Stephanie H. Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Sugirthan Sivalingam
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Franziska Degenhardt
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Andreas J. Forstner
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen
- Peter Falkai
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich
- Thomas G. Schulze
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- Urs Heilbronner
- Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich
- DOI
- https://doi.org/10.1186/s40345-019-0176-6
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 12
Abstract
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.
Keywords
