Department of Molecular and Translational Medicine, Biology and Genetic Division, University of Brescia, Viale Europa, 11, 25123, Brescia, Italy.
Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
Clin Epigenetics. 2024 Jul 17;16(1):93. doi: 10.1186/s13148-024-01704-z.
Electroconvulsive therapy (ECT) benefits patients with treatment-resistant depression (TRD), but the underlying biological processes are unclear. We conducted an epigenome-wide association study in 32 TRD patients undergoing ECT to depict ECT-associated methylation changes. Illness severity and ECT outcomes were assessed with the Montgomery-Åsberg Depression Rating Scale at baseline (T0) and 1 month after its end (T1). Methylation was profiled at T0 and T1 with the Illumina Infinium Methylation EPIC BeadChip array.
Longitudinal T0-T1 analyses showed 3 differentially methylated probes (DMPs) with nominal p values ≤ 10, with 2 annotated in the genes CYB5B and PVRL4. Including covariates, we found 4 DMPs for symptoms variation, annotated in FAM20C, EPB41, OTUB1 and ADARB1, and 3 DMPs for response status, with 2 annotated in IQCE and FAM20C. Regional analysis revealed 54 differentially methylated regions (DMRs) with nominal p value area ≤ 0.05, with 9 presenting adjusted p-value area ≤ 0.10, annotated in MCF2L, SLC25A24, RUNX3, MIR637, FOXK2, FAM180B, POU6F1, ALS2CL and CCRL2. Considering covariates, we found 21 DMRs for symptoms variation and 26 DMRs for response (nominal p value area ≤ 0.05), with 4 presenting adjusted p-value area ≤ 0.10 for response, annotated in SNORD34, NLRP6, GALNT2 and SFT2D3. None remained significant after false discovery rate correction. Notably, ADARB1 variants are associated with suicide attempt in patients with psychiatric disorders, and SLC25A24 relates to conduct disorder. Several DMPs and DMRs are annotated in genes associated with inflammatory/immune processes. Longitudinal analyses on females (n = 22) revealed statistically significant DMRs (adjusted p value area ≤ 0.05) and trend-significant DMRs (adjusted p value area ≤ 0.07) for symptoms variation and response status, annotated in genes related to psychiatric disorders (ZFP57, POLD4, TRIM10, GAS7, ADORA2A, TOLLIP), trauma exposure (RIPOR2) and inflammatory/immune responses (LAT, DLX4, POLD4, FAM30A, H19). Pathway analysis on females revealed enrichment for transcriptional activity, growth factors, DNA maintenance, and immune pathways including IRF7 and IRF2.
Although no significant results were found for the whole cohort, the study provides insights into ECT-associated methylation changes, highlighting DMPs and DMRs related to ECT outcomes. Analyses on females revealed significant DMRs and pathways related to psychiatric disorders and inflammatory/immune processes.
电抽搐疗法（ECT）对治疗抵抗性抑郁症（TRD）患者有益，但潜在的生物学过程尚不清楚。我们对 32 名接受 ECT 的 TRD 患者进行了全基因组关联研究，以描绘 ECT 相关的甲基化变化。在基线（T0）和结束后 1 个月（T1），使用蒙哥马利-阿斯伯格抑郁评定量表评估疾病严重程度和 ECT 结果。T0 和 T1 时使用 Illumina Infinium Methylation EPIC BeadChip 阵列进行甲基化分析。
纵向 T0-T1 分析显示有 3 个具有名义 p 值≤10 的差异甲基化探针（DMP），其中 2 个注释在 CYB5B 和 PVRL4 基因中。包括协变量后，我们发现 4 个用于症状变化的 DMP，注释在 FAM20C、EPB41、OTUB1 和 ADARB1 中，3 个用于反应状态的 DMP，其中 2 个注释在 IQCE 和 FAM20C 中。区域分析显示有 54 个差异甲基化区域（DMR），名义 p 值区域≤0.05，其中 9 个具有调整后的 p 值区域≤0.10，注释在 MCF2L、SLC25A24、RUNX3、MIR637、FOXK2、FAM180B、POU6F1、ALS2CL 和 CCRL2 中。考虑到协变量，我们发现 21 个用于症状变化，26 个用于反应的 DMR（名义 p 值区域≤0.05），其中 4 个用于反应的 DMR 具有调整后的 p 值区域≤0.10，注释在 SNORD34、NLRP6、GALNT2 和 SFT2D3 中。在假发现率校正后，没有一个结果仍然显著。值得注意的是，ADARB1 变体与精神障碍患者的自杀企图有关，SLC25A24 与行为障碍有关。几个 DMP 和 DMR 注释在与炎症/免疫过程相关的基因中。对女性（n=22）的纵向分析显示，对于症状变化和反应状态有统计学显著的 DMR（调整后的 p 值区域≤0.05）和趋势显著的 DMR（调整后的 p 值区域≤0.07），注释在与精神障碍（ZFP57、POLD4、TRIM10、GAS7、ADORA2A、TOLLIP）、创伤暴露（RIPOR2）和炎症/免疫反应（LAT、DLX4、POLD4、FAM30A、H19）相关的基因中。对女性的途径分析显示，转录活性、生长因子、DNA 维持以及包括 IRF7 和 IRF2 在内的免疫途径富集。
尽管整个队列没有发现显著结果，但该研究提供了 ECT 相关甲基化变化的见解，突出了与 ECT 结果相关的 DMP 和 DMR。对女性的分析显示，与精神障碍和炎症/免疫过程相关的有意义的 DMR 和途径。
