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Int J Bipolar Disord. 2020 Feb 12;8(1):9. doi: 10.1186/s40345-019-0176-6.

The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder.

Author information

1
Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany. Ashley.Comes@med.uni-muenchen.de.
2
International Max Planck Research School for Translational Psychiatry (IMPRS-TP), 80804, Munich, Germany. Ashley.Comes@med.uni-muenchen.de.
3
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804, Munich, Germany.
4
Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
5
Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, 80336, Munich, Germany.
6
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075, Göttingen, Germany.
7
Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675, Munich, Germany.
8
International Max Planck Research School for Translational Psychiatry (IMPRS-TP), 80804, Munich, Germany.
9
Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, 44791, Bochum, Germany.
10
Department of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, University of Augsburg, 86156, Augsburg, Germany.
11
Psychiatrieverbund Oldenburger Land gGmbH, Karl-Jaspers-Klinik, 26160, Bad Zwischenahn, Germany.
12
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
13
Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, 8036, Graz, Austria.
14
Department of Psychiatry, Dr. Frontheim-Mental Health, 38704, Liebenburg, Germany.
15
Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, 27356, Rotenburg, Germany.
16
Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, 26160, Oldenburg, Germany.
17
Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, 37269, Eschwege, Germany.
18
Asklepios Specialized Hospital, 37081, Göttingen, Germany.
19
AMEOS Clinical Center Hildesheim, 31135, Hildesheim, Germany.
20
Center für Systems Neuroscience (ZSN) Hannover, 30559, Hannover, Germany.
21
Department of Psychiatry, Medical School of Hannover, 30625, Hannover, Germany.
22
Psychiatric Hospital Lüneburg, 21339, Lüneburg, Germany.
23
AMEOS Clinical Center Osnabrück, 49088, Osnabrück, Germany.
24
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany.
25
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, 53127, Bonn, Germany.
26
Center for Human Genetics, University of Marburg, 35033, Marburg, Germany.
27
Department of Biomedicine, University of Basel, 4031, Basel, Switzerland.
28
Department of Psychiatry (UPK), University of Basel, 4002, Basel, Switzerland.
29
German Center for Neurodegenerative Diseases (DZNE), 37075, Göttingen, Germany.
30
iBiMED, Medical Sciences Department, University of Aveiro, 3810-193, Aveiro, Portugal.

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:

Bipolar disorder; DNA methylation; Epigenetic aging; Epigenomics; Longitudinal; Stressful life events

PMID:
32048126
DOI:
10.1186/s40345-019-0176-6

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