Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
Int J Neuropsychopharmacol. 2024 Nov 1;27(11). doi: 10.1093/ijnp/pyae045.
Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment nonresponse rates are high. Recent years have seen an increase in research into predictive biomarkers toward improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the largest sample to date of patients with MDD.
Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of n = 230 Caucasian patients with MDD receiving 6-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of n = 107 patients primarily receiving continuous treatment with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. Treatment response was assessed by means of the Hamilton Depression Scale.
No genome-wide significant hits were observed. Suggestive (P < 1E-5) epigenome-wide evidence was discerned for altered DNA methylation at 6 CpG sites (LOC102724467, LOC100506023, RSPO2, SAG, IL16, PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors, differential DNA methylation at 11 CpGs, for example, mapping to the TIMP2, VDAC1, or SORL1 genes, was suggestively associated with treatment response.
The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision-making toward more individualized and thus more efficacious treatments of MDD.
尽管抗抑郁药治疗重度抑郁症（MDD）的疗效已有充分记录，但初始治疗无反应率仍然很高。近年来，人们越来越关注预测生物标志物，以改善诊断和个体化治疗。在这些标志物中，DNA 甲基化等表观遗传机制是预测 MDD 抗抑郁治疗反应的有前途的候选标志物。本研究旨在针对迄今为止最大的 MDD 患者样本，探讨全基因组 DNA 甲基化为抗抑郁治疗反应的预测因子。
使用 Infinium MethylationEPIC BeadChip 分析了 230 名接受自然住院环境下 6 周抗抑郁治疗的白种人 MDD 患者以及 107 名主要接受选择性 5-羟色胺再摄取抑制剂或 5-羟色胺和去甲肾上腺素再摄取抑制剂连续治疗的患者的外周血全基因组 DNA 甲基化。采用汉密尔顿抑郁量表评估治疗反应。
未观察到全基因组显著命中。在预测自然抗抑郁治疗反应方面，发现了 6 个 CpG 位点（LOC102724467、LOC100506023、RSPO2、SAG、IL16、PRKCI）的 DNA 甲基化改变的提示性（P<1E-5）全基因组范围内的证据。在接受选择性 5-羟色胺再摄取抑制剂或 5-羟色胺和去甲肾上腺素再摄取抑制剂治疗的患者中，例如，映射到 TIMP2、VDAC1 或 SORL1 基因的 11 个 CpG 差异 DNA 甲基化与治疗反应呈提示性相关。
本研究结果初步证明了 DNA 甲基化模式与 MDD 的抗抑郁治疗反应相关。如果在独立且更大的样本中得到显著复制，这些发现将来可能有助于临床决策，实现更个体化和更有效的 MDD 治疗。
