Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University, Daejeon, Republic of Korea.
Department of Neuropsychiatry, School of Medicine, Eulji University, Daejeon, Republic of Korea.
Psychiatry Investig. 2015 Apr;12(2):249-59. doi: 10.4306/pi.2015.12.2.249. Epub 2015 Mar 18.
Currently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum.
Blood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed.
The quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together.
This is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation.
目前,有一些生物标志物可辅助诊断和治疗抑郁症。然而,这些标志物的数量还不够。我们试图通过对血清进行定量蛋白质组学分析,鉴定抑郁情绪期间差异表达的蛋白质,作为潜在的诊断生物标志物。
从 5 例重度抑郁症(MDD)患者在治疗前的抑郁状态和治疗期间的缓解状态下采集两次血样。通过液相色谱-串联质谱法对蛋白质谱进行个体分析。通过无标记定量分析差异表达蛋白。酶联免疫吸附试验(ELISA)结果和受试者工作特征(ROC)曲线用于验证差异表达蛋白。为了验证,对 8 例 MDD 患者(包括 3 例额外患者和 8 例匹配的正常对照者)进行了分析。
定量蛋白质组学研究鉴定出 10 种在 5 例 MDD 患者中一致上调或下调的蛋白。ELISA 产生的结果与 3 种蛋白质的蛋白质组学分析结果一致。正常对照组和 MDD 患者之间的表达水平差异显著。3 种蛋白分别为铜蓝蛋白、α-胰蛋白酶抑制剂重链 H4 和补体成分 1qC,在抑郁状态下表达上调。这些蛋白的 ROC 曲线可将抑郁状态与缓解状态区分开来,当同时分析这 3 种蛋白时,这种区分效果增强。
这是第一项比较基于情绪的个体内差异的 MDD 患者的蛋白质组学研究。该技术可能是识别 MDD 生物标志物的有用方法,但需要进一步的蛋白质组学研究进行验证。