Schwarz Emanuel, Bahn Sabine
Institute of Biotechnology, University of Cambridge, Cambridge, UK.
Electrophoresis. 2008 Jul;29(13):2884-90. doi: 10.1002/elps.200700710.
Schizophrenia is a multifaceted neuropsychiatric disorder. Its onset is the result of complex interactions between genetic, developmental and environmental factors. It almost certainly presents a heterogeneous group of aetiologies which may not be reflected in the symptomatic/clinical presentation of patients. Therefore, a better molecular understanding of the disease onset and progression is urgently needed. The high complexity of the disorder and the heterogeneity of patient populations account for the slow progress of biomarker discovery approaches. Multi-omics profiling approaches can be employed to investigate large numbers of patient and control samples in a single experiment. These large scale experiments are required to identify disease intrinsic molecular signatures as well as patient subgroups with potentially distinct biochemical pathways underpinning their symptoms. In this overview, we describe some of the most important challenges for biomarker discovery for psychiatric disorders and emphasize how these problems contribute to the requirement of large sample numbers. Results of MS-based protein profiling studies in schizophrenia research are reviewed and technical advantages and difficulties of the methodologies described. We outline recent technological advances that generated impressive results in other areas of research and point to their applicability for biomarker discovery in psychiatric disorders.
精神分裂症是一种多方面的神经精神疾病。其发病是遗传、发育和环境因素之间复杂相互作用的结果。几乎可以肯定的是，它呈现出一组异质性的病因，这可能不会在患者的症状/临床表现中体现出来。因此，迫切需要从分子层面更好地理解该疾病的发病和进展。该疾病的高度复杂性以及患者群体的异质性导致生物标志物发现方法进展缓慢。多组学分析方法可用于在单个实验中研究大量患者和对照样本。需要进行这些大规模实验来识别疾病内在的分子特征以及具有潜在不同生化途径支撑其症状的患者亚组。在本综述中，我们描述了精神疾病生物标志物发现面临的一些最重要挑战，并强调这些问题如何导致需要大量样本。回顾了基于质谱的蛋白质谱分析研究在精神分裂症研究中的结果，并描述了这些方法的技术优势和困难。我们概述了近期在其他研究领域取得显著成果的技术进展，并指出它们在精神疾病生物标志物发现中的适用性。
