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
Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
International Max Planck Research School for Translational Psychiatry (IMPRS-TP), 80804, Munich, Germany.
Int J Bipolar Disord. 2020 Feb 12;8(1):9. doi: 10.1186/s40345-019-0176-6.
Stressful life events influence the course of affective disorders, however, the mechanisms by which they bring about phenotypic change are not entirely known.
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.
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). Epigenetic aging over a 1-year period was not associated with changes in stress or symptom measures.
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.
应激性生活事件会影响情感障碍的病程，然而，其导致表型变化的机制尚不完全清楚。
我们在一项来自纵向PsyCourse研究的双相情感障碍患者队列（n = 96）中，探讨了DNA甲基化在应对近期应激性生活事件中的作用。在两个时间点对超过850,000个甲基化位点进行外周血DNA甲基化组分析。首先通过研究先前与应激反应相关的候选基因附近的甲基化位点，其次通过进行全表观基因组关联分析，评估应激性生活事件的影响评分与DNA甲基化之间的关联。第三，研究表观遗传衰老与应激和症状指标随时间变化之间的关联。
对甲基化特征随时间的研究表明，在1年的时间里，超过一半的测试CpG位点甲基化的绝对差异至少为1%。尽管没有一个CpG位点在多重检验校正后仍具有统计学意义，但一个位点（cg15212455）的甲基化与应激性生活事件存在提示性关联（p < 1.0×10）。1年期间的表观遗传衰老与应激或症状指标的变化无关。
据我们所知，我们的研究首次在双相情感障碍患者中，跨时间研究全表观基因组甲基化，并与近期非创伤性应激性生活事件相关。有限且不确定的证据表明，未来需要在更大样本的特征明确的双相情感障碍患者中进行纵向研究，以全面了解DNA甲基化在双相情感障碍病程中的作用。
