Identifying Plasma Biomarkers with high specificity for major depressive disorder: A multi-level proteomics study.
Identifying Plasma Biomarkers with high specificity for major depressive disorder: A multi-level proteomics study.
复制标题
DOI：
10.1016/j.jad.2020.08.078
复制
发表时间：
2020-09
影响因子：
6.6
通讯作者：
Yachen Shi;R. Song;Liping Wang;Yang-Jian Qi;Hongxing Zhang;Jianli Zhu;Xiaobin Zhang;Xiaowei Tang;Qiongqiong Zhan;Yang Zhao;D. Swaab;Ai-min Bao;Zhijun Zhang
中科院分区：
文献类型：
--
作者：
Yachen Shi;R. Song;Liping Wang;Yang-Jian Qi;Hongxing Zhang;Jianli Zhu;Xiaobin Zhang;Xiaowei Tang;Qiongqiong Zhan;Yang Zhao;D. Swaab;Ai-min Bao;Zhijun Zhang
背景由于抑郁症的生物学复杂性，目前尚无诊断抑郁症的客观生物标志物。基于血液的生物标志物的存在，具有高度的特异性将是方便的临床诊断的MDD.MethodsA全面的血浆蛋白质组学分析进行了高度同质的队列[7药物初治MDD患者和7健康对照（HC）]，与生物信息学分析相结合的机器学习用于筛选候选蛋白质。在独立队列[60例HC和74例MDD、42例精神分裂症（SZ）和39例双相I型障碍（BD-I）药物初治患者]中进行了重现性和特异性验证。此外，验证的一致性，完成了16例MDD患者和16例HC的死后脑组织的蛋白质组学分析。结果如下：在发现队列和独立重复队列中，MDD患者的C反应蛋白（CRP）、抗凝血酶III（ATIII）、α-胰蛋白酶抑制剂间重链4（ITIH 4）和维生素D结合蛋白（VDB）水平均显著较高。与SZ或BD-I患者相比，两种蛋白质（VDB和ITIH 4）仅在MDD患者中显著升高。此外，在MDD患者的血浆和死后背外侧前额叶皮质组织中观察到VDB和ITIH 4的增加。此外，由所有四种血浆蛋白组成的面板能够区分MDD患者与HC或SZ或BD-I patients.ConclusionPlasma ITIH 4和VDB具有最高的准确性，可能是MDD的潜在血浆生物标志物，具有高度特异性。四蛋白组更适合作为MDD的潜在临床诊断标志物。
BackgroundThere are currently no objective diagnostic biomarkers for major depressive disorder (MDD) due to the biological complexity of the disorder. The existence of blood-based biomarkers with high specificity would be convenient for the clinical diagnosis of MDD.MethodsA comprehensive plasma proteomic analysis was conducted in a highly homogeneous cohort [7 drug-naïve MDD patients and 7 healthy controls (HCs)], with bioinformatics analysis combined with machine learning used to screen candidate proteins. Verification of reproducibility and specificity was conducted in independent cohorts [60 HCs and 74 MDD, 42 schizophrenia (SZ) and 39 bipolar I disorder (BD-I) drug-naïve patients]. Furthermore, verification of consistency was accomplished by proteomic analysis of postmortem brain tissue from 16 MDD patients and 16 HCs. Results: Levels of C-reactive protein (CRP), antithrombin III (ATIII), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and vitamin D-binding protein (VDB) were significantly higher in MDD patients, both in the discovery cohort and independent replication cohort. In comparison with SZ or BD-I patients, two proteins (VDB and ITIH4) were significantly elevated only in MDD patients. In addition, increased VDB and ITIH4 were observed consistently in both plasma and postmortem dorsolateral prefrontal cortex tissues of MDD patients. Furthermore, a panel consisting of all four plasma proteins was able to distinguish MDD patients from HCs or SZ or BD-I patients with the highest accuracy.ConclusionPlasma ITIH4 and VDB may be potential plasma biomarkers of MDD with high specificity. The four-protein panel is more suitable as a potential clinical diagnostic marker for MDD.