Van Assche Evelien, Hohoff Christa, Su Atil Ecem, Wissing Sophia M, Serretti Alessandro, Fabbri Chiara, Pisanu Claudia, Squassina Alessio, Minelli Alessandra, Baune Bernhard T
Department of Psychiatry, University of Münster, Münster, Germany.
Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
Brain Behav Immun. 2025 Jan;123:597-605. doi: 10.1016/j.bbi.2024.09.026. Epub 2024 Sep 26.
Alterations in DNA methylation and inflammation could represent valid biomarkers for the stratification of patients with major depressive disorder (MDD). This study explored the use of DNA-methylation based immunological cell-type profiles in the context of MDD and symptom severity over time. In 119 individuals with MDD, DNA-methylation was assessed on whole blood using the Illumina Infinium MethylationEPIC 850 k BeadChip. Quality control and data processing, as well as cell type estimation was conducted using the RnBeads package. The cell type composition was estimated using epigenome-wide DNA methylation signatures, applying the Houseman method, considering six cell types (neutrophils, natural killer cells (NK), B cells, CD4+ T cells, CD8+ T cells and monocytes). Two cytokines (IL-6 and IL-1β) and hsCRP were quantified in serum. We performed a hierarchical cluster analysis on the six estimated cell-types and tested the differences between these clusters in relation to the two cytokines and hsCRP, depression severity at baseline, and after 6 weeks of treatment (celecoxib/placebo + vortioxetine). We performed a second cluster analysis with cell-types and cytokines combined. ANCOVA was used to test for differences across clusters. We applied the Bonferroni correction. After quality control, we included 113 participants. Two clusters were identified, cluster 1 was high in CD4+ cells and NK, cluster 2 was high in CD8+ T-cells and B-cells, with similar fractions of neutrophils and monocytes. The clusters were not associated with either of the two cytokines and hsCRP, or depression severity at baseline, but cluster 1 showed higher depression severity after 6 weeks, corrected for baseline (p = 0.0060). The second cluster analysis found similar results: cluster 1 was low in CD8+ T-cells, B-cells, and IL-1β. Cluster 2 was low in CD4+ cells and natural killer cells. Neutrophils, monocytes, IL-6 and hsCRP were not different between the clusters. Participants in cluster 1 showed higher depression severity at baseline than cluster 2 (p = 0.034), but no difference in depression severity after 6 weeks. DNA-methylation based cell-type profiles may be valuable in the immunological characterization and stratification of patients with MDD. Future models should consider the inclusion of more cell-types and cytokines for better a prediction of treatment outcomes.
DNA甲基化和炎症的改变可能是重度抑郁症（MDD）患者分层的有效生物标志物。本研究探讨了基于DNA甲基化的免疫细胞类型谱在MDD及症状严重程度随时间变化方面的应用。在119例MDD患者中，使用Illumina Infinium MethylationEPIC 850k BeadChip对全血进行DNA甲基化评估。使用RnBeads软件包进行质量控制、数据处理以及细胞类型估计。采用Houseman方法，考虑六种细胞类型（中性粒细胞、自然杀伤细胞（NK）、B细胞、CD4 + T细胞、CD8 + T细胞和单核细胞），通过全基因组DNA甲基化特征估计细胞类型组成。在血清中定量两种细胞因子（IL - 6和IL - 1β）和hsCRP。我们对六种估计的细胞类型进行了层次聚类分析，并测试了这些聚类在两种细胞因子、hsCRP、基线时的抑郁严重程度以及治疗6周后（塞来昔布/安慰剂 + 伏硫西汀）的差异。我们对细胞类型和细胞因子进行了第二次聚类分析。使用协方差分析测试聚类间的差异。我们应用了Bonferroni校正。质量控制后，纳入了113名参与者。识别出两个聚类，聚类1中CD4 + 细胞和NK细胞含量高，聚类2中CD8 + T细胞和B细胞含量高，中性粒细胞和单核细胞比例相似。这些聚类与两种细胞因子、hsCRP以及基线时的抑郁严重程度均无关联，但聚类1在6周后经基线校正后的抑郁严重程度更高（p = 0.0060）。第二次聚类分析得到了类似的结果：聚类1中CD8 + T细胞、B细胞和IL - 1β含量低。聚类2中CD4 + 细胞和自然杀伤细胞含量低。聚类间中性粒细胞、单核细胞、IL - 6和hsCRP无差异。聚类1中的参与者在基线时的抑郁严重程度高于聚类2（p = 0.034），但6周后的抑郁严重程度无差异。基于DNA甲基化的细胞类型谱可能对MDD患者的免疫学特征和分层有价值。未来的模型应考虑纳入更多细胞类型和细胞因子，以更好地预测治疗结果。
