Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan.
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
Sci Rep. 2021 Jan 27;11(1):2296. doi: 10.1038/s41598-021-81758-8.
The heterogeneity of major depressive disorder (MDD) is attributed to the fact that diagnostic criteria (e.g., DSM-5) are only based on clinical symptoms. The discovery of blood biomarkers has the potential to change the diagnosis of MDD. The purpose of this study was to identify blood biomarkers of DNA methylation by strategically subtyping patients with MDD by onset age. We analyzed genome-wide DNA methylation of patients with adult-onset depression (AOD; age ≥ 50 years, age at depression onset < 50 years; N = 10) and late-onset depression (LOD; age ≥ 50 years, age at depression onset ≥ 50 years; N = 25) in comparison to that of 30 healthy subjects. The methylation profile of the AOD group was not only different from that of the LOD group but also more homogenous. Six identified methylation CpG sites were validated by pyrosequencing and amplicon bisulfite sequencing as potential markers for AOD in a second set of independent patients with AOD and healthy control subjects (N = 11). The combination of three specific methylation markers achieved the highest accuracy (sensitivity, 64%; specificity, 91%; accuracy, 77%). Taken together, our findings suggest that DNA methylation markers are more suitable for AOD than for LOD patients.
重度抑郁症（MDD）的异质性归因于这样一个事实，即诊断标准（例如 DSM-5）仅基于临床症状。血液生物标志物的发现有可能改变 MDD 的诊断。本研究的目的是通过根据发病年龄对 MDD 患者进行策略性亚型分类来确定 DNA 甲基化的血液生物标志物。我们分析了成年发病抑郁（AOD；年龄≥50 岁，抑郁发病年龄＜50 岁；N=10）和晚发抑郁（LOD；年龄≥50 岁，抑郁发病年龄≥50 岁；N=25）患者与 30 名健康受试者的全基因组 DNA 甲基化。AOD 组的甲基化谱不仅与 LOD 组不同，而且更同质。通过焦磷酸测序和扩增子亚硫酸氢盐测序验证了六个确定的甲基化 CpG 位点，作为第二组独立的 AOD 患者和健康对照（N=11）中 AOD 的潜在标志物。三个特定甲基化标志物的组合实现了最高的准确性（灵敏度 64%，特异性 91%，准确性 77%）。总之，我们的研究结果表明，与 LOD 患者相比，DNA 甲基化标志物更适合 AOD。
