Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections.
Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections.
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DOI：
10.1371/journal.pone.0009166
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发表时间：
2010-02-11
期刊：
影响因子：
3.7
通讯作者：
Muglia P
中科院分区：
文献类型：
--
作者：
Domenici E;Willé DR;Tozzi F;Prokopenko I;Miller S;McKeown A;Brittain C;Rujescu D;Giegling I;Turck CW;Holsboer F;Bullmore ET;Middleton L;Merlo-Pich E;Alexander RC;Muglia P
尽管有大量的研究工作旨在了解精神疾病的神经生物学基础，但这些疾病的诊断和治疗评价仍然仅仅基于对症状的相对主观的评估。因此，生物标记物，可以改善目前的精神病学障碍的分类，并在生物学基础上的角度分层患者到更同质的临床不同的亚组，是非常需要的。为了确定新的候选生物标记物的抑郁症和精神分裂症，我们已经应用了一个集中的蛋白质组学方法，使用血浆样本从一个大的病例对照集合。使用结构化访谈根据DSM标准对患者进行诊断，并评估了许多其他临床变量和人口统计信息。来自245名抑郁症患者、229名精神分裂症患者和254名对照的血浆样本被提交给多分析物分析，允许对多达79种蛋白质进行评估，包括一系列先前被认为参与抑郁症和精神分裂症的病理生理学的细胞因子、趋化因子和神经营养因子。单变量数据分析显示了比偶然预期更显著的p值，并强调了属于先前怀疑参与重度抑郁症或精神分裂症病理生理学的途径或机制的几种蛋白质，如抑郁症的胰岛素和MMP-9，以及精神分裂症的BDNF，EGF和一些趋化因子。进行多变量分析以提高病例与对照的区分，并确定信息量最大的标志物组。这些结果说明了在大量收集中进行的精神疾病血浆生物标志物分析的潜力。该研究强调了一组分析物作为抑郁症和精神分裂症的候选生物标志物特征，并在独立收集中进行了进一步研究。
Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections.
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