The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder
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The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder. / Comes, Ashley L; Czamara, Darina; Adorjan, Kristina; Anderson-Schmidt, Heike; Andlauer, Till F M; Budde, Monika; Gade, Katrin; Hake, Maria; Kalman, Janos L; Papiol, Sergi; Reich-Erkelenz, Daniela; Klöhn-Saghatolislam, Farah; Schaupp, Sabrina K; Schulte, Eva C; Senner, Fanny; Juckel, Georg; Schmauß, Max; Zimmermann, Jörg; Reimer, Jens; Reininghaus, Eva; Anghelescu, Ion-George; Konrad, Carsten; Thiel, Andreas; Figge, Christian; von Hagen, Martin; Koller, Manfred; Dietrich, Detlef E; Stierl, Sebastian; Scherk, Harald; Witt, Stephanie H; Sivalingam, Sugirthan; Degenhardt, Franziska; Forstner, Andreas J; Rietschel, Marcella; Nöthen, Markus M; Wiltfang, Jens; Falkai, Peter; Schulze, Thomas G; Heilbronner, Urs.
In: INT J BIPOLAR DISORD, Vol. 8, No. 1, 12.02.2020, p. 9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The role of environmental stress and DNA methylation in the longitudinal course of bipolar disorder
AU - Comes, Ashley L
AU - Czamara, Darina
AU - Adorjan, Kristina
AU - Anderson-Schmidt, Heike
AU - Andlauer, Till F M
AU - Budde, Monika
AU - Gade, Katrin
AU - Hake, Maria
AU - Kalman, Janos L
AU - Papiol, Sergi
AU - Reich-Erkelenz, Daniela
AU - Klöhn-Saghatolislam, Farah
AU - Schaupp, Sabrina K
AU - Schulte, Eva C
AU - Senner, Fanny
AU - Juckel, Georg
AU - Schmauß, Max
AU - Zimmermann, Jörg
AU - Reimer, Jens
AU - Reininghaus, Eva
AU - Anghelescu, Ion-George
AU - Konrad, Carsten
AU - Thiel, Andreas
AU - Figge, Christian
AU - von Hagen, Martin
AU - Koller, Manfred
AU - Dietrich, Detlef E
AU - Stierl, Sebastian
AU - Scherk, Harald
AU - Witt, Stephanie H
AU - Sivalingam, Sugirthan
AU - Degenhardt, Franziska
AU - Forstner, Andreas J
AU - Rietschel, Marcella
AU - Nöthen, Markus M
AU - Wiltfang, Jens
AU - Falkai, Peter
AU - Schulze, Thomas G
AU - Heilbronner, Urs
PY - 2020/2/12
Y1 - 2020/2/12
N2 - 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.
AB - 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.
U2 - 10.1186/s40345-019-0176-6
DO - 10.1186/s40345-019-0176-6
M3 - SCORING: Journal article
C2 - 32048126
VL - 8
SP - 9
JO - INT J BIPOLAR DISORD
JF - INT J BIPOLAR DISORD
SN - 2194-7511
IS - 1
ER -
