Department of Psychiatry and Psychotherapy, University Hospital Tübingen, Calwerstr. 14, 72076, Tübingen, Germany.
Graduate Training Centre of Neuroscience, University of Tübingen, Tübingen, Germany.
Clin Epigenetics. 2018 Aug 22;10(1):109. doi: 10.1186/s13148-018-0544-6.
The importance of epigenetic alterations in psychiatric disorders is increasingly acknowledged and the use of DNA methylation patterns as markers of disease is a topic of ongoing investigation. Recent studies suggest that patients suffering from Borderline Personality Disorder (BPD) display differential DNA methylation of various genes relevant for neuropsychiatric conditions. For example, several studies report differential methylation in the promoter region of the brain-derived neurotrophic factor gene (BDNF) in blood. However, little is known about BDNF methylation in other tissues.
In the present study, we analyzed DNA methylation of the BDNF IV promoter in saliva and blood of 41 BPD patients and 41 matched healthy controls and found significant hypermethylation in the BPD patient's saliva, but not blood. Further, we report that BDNF methylation in saliva of BPD patients significantly decreased after a 12-week psychotherapeutic intervention.
Providing a direct comparison of BDNF methylation in blood and saliva of the same individuals, our results demonstrate the importance of choice of tissue for the study of DNA methylation. In addition, they indicate a better suitability of saliva for the study of differential BDNF methylation in BPD patients. Further, our data appear to indicate a reversal of disease-specific alterations in BDNF methylation in response to psychotherapy, though further experiments are necessary to validate these results and determine the specificity of the effect.
精神疾病中表观遗传改变的重要性越来越受到认可，并且 DNA 甲基化模式作为疾病标志物的应用是一个正在研究的课题。最近的研究表明，患有边缘型人格障碍（BPD）的患者表现出与神经精神疾病相关的各种基因的 DNA 甲基化差异。例如，几项研究报告了在血液中脑源性神经营养因子基因（BDNF）的启动子区域存在差异甲基化。然而，关于其他组织中的 BDNF 甲基化知之甚少。
在本研究中，我们分析了 41 名 BPD 患者和 41 名匹配的健康对照者唾液和血液中的 BDNF IV 启动子的 DNA 甲基化，发现 BPD 患者唾液中的 BDNF 呈显著高甲基化，但血液中无此现象。此外，我们报告称，BPD 患者唾液中的 BDNF 甲基化在 12 周心理治疗干预后显著降低。
提供了对同一个体血液和唾液中 BDNF 甲基化的直接比较，我们的结果表明了研究 DNA 甲基化时组织选择的重要性。此外，它们表明唾液更适合研究 BPD 患者中 BDNF 甲基化的差异。此外，我们的数据似乎表明，BDNF 甲基化的疾病特异性改变在心理治疗后出现逆转，尽管需要进一步的实验来验证这些结果并确定该效应的特异性。
