Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Transl Psychiatry. 2021 Jun 5;11(1):347. doi: 10.1038/s41398-021-01474-9.
Electroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák's p = 0.0031) and 20 (Šídák's p = 4.2 × 10) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.
电抽搐治疗（ECT）是一种快速起效且强效的抗抑郁治疗方法，被认为对治疗严重和药物治疗抵抗的抑郁症有效。最近的研究表明，表观遗传机制可以介导治疗反应，目前关于 ECT 效果与 DNA 甲基化之间关系的研究主要采用候选方法。在本研究中，我们检测了 ECT 对接受治疗的抑郁症患者（n=34）反应相关的甲基组的影响，在第一次和最后一次 ECT 治疗前检测差异甲基化 CpG 位点。我们发现一个与 ECT 反应效果相关的差异甲基化 CpG 位点（定义为汉密尔顿抑郁量表评分下降>50%，HDRS），TNKS（q<0.05;p=7.15×10）。当连续定义反应（ΔHDRS）时，FKBP5 上的差异甲基化 CpG 位点最具提示性（p=3.94×10）。区域分析确定了两个与ΔHDRS 相关的差异甲基化区域，位于 8 号染色体（Šídák 的 p=0.0031）和 20 号染色体（Šídák 的 p=4.2×10）上。功能途径分析未发现任何显著途径。对先前提出的与 ECT 机制相关的候选物进行验证性检查，仅在名义上显著水平（p<0.05）发现与反应相关的 CpG 位点。尽管样本量有限，但本研究能够鉴定与 ECT 反应相关的表观遗传变化，这表明这种方法，特别是当涉及更大的样本时，有可能为研究 ECT 和严重及治疗抵抗性抑郁症相关的机制提供信息。
