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[精神病学中的生物标志物进展如何?]

[How far have biomarkers in psychiatry advanced?].

作者信息

Hashimoto Ryota, Yasuda Yuka, Yamamori Hidenaga, Fujimoto Michiko, Ohi Kazutaka, Fukumoto Motoyuki, Umeda-Yano Satomi, Takeda Masatoshi

机构信息

Department of Psychiatry, Osaka University Graduate School of Medicine.

Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University.

出版信息

Seishin Shinkeigaku Zasshi. 2013;115(12):1203-10.

Abstract

A biomarker is defined as a biological indicator of normal or pathological processes, and a pharmacological response to a therapeutic intervention, whose characteristics can be measured and evaluated objectively. In medicine and health, biomarkers can be paraphrased as diagnostic methods objectively conducive to treatment. Here, we discuss biomarkers of schizophrenia as a representative mental illness, whose research has advanced compared with that of other disorders. Schizophrenia is a syndrome with a typical course and symptoms. Its pathophysiology and pathogenesis have not been elucidated (medically however, its underlying biological mechanisms are assumed to be present. That is, in biomarker discovery, when the pathogenesis and cause are elucidated, the patient group would not consiste of schizophrenia but, it is a new disease of "x x disease." For example, neurosyphilis is exogenous psychosis, by finding a biomarker of syphilis spirochete, a new disease concept of neurosyphilis could be distinguished from the schizophrenia). In this way, it can be said that biomarker research is essential for the development of new diagnostic and treatment methods for mental illness. There are several biomarker research methods such as genetic analysis, biological sample analysis, cognitive analysis, neurophysiology, neuroimaging, animal models, and post-mortem brain analysis. Further, studies have been made, however, biomarkers that can explain all of schizophrenia has not been found yet. As schizophrenia is assumed to be a heterogenous syndrome, it is believed that the etiology varies. Thus, there is a possibility that targeting schizophrenia as a whole will make it difficulty to find biomarkers for patients with schizophrenia. It is considered that appropriate subgroup analysis is needed. In order to overcome it, amount-of-resources strategy to find patients by using large of samples has been made mainly in Europe and the United States. In Japan, we have used sub-group analysis strategy to elaborate this issue such as the use of an intermediate phenotype. It is not possible to research a similar strategy, because of the limited funds and manpower in Japan compared to U. S. and Europe. As nationwide research organizations in Japan, such as IGC (Imaging genetics consortium), combination analysis of genetics and neuroimaging and COCORO (Cognitive genetics collaborative research organization), combination analysis of genetics and cognitive function, have been established, the development of biomarkers for mental illnesses is expected in the near future.

摘要

生物标志物被定义为正常或病理过程以及对治疗干预的药理反应的生物学指标,其特征可以被客观地测量和评估。在医学和健康领域,生物标志物可以被解释为客观上有利于治疗的诊断方法。在此,我们将讨论精神分裂症这一具有代表性的精神疾病的生物标志物,相较于其他疾病,其研究进展更为显著。精神分裂症是一种具有典型病程和症状的综合征。其病理生理学和发病机制尚未阐明(然而在医学上,假定其潜在的生物学机制是存在的。也就是说,在生物标志物发现过程中,当发病机制和病因被阐明时,患者群体将不再是精神分裂症患者,而是一种“xx疾病”的新疾病。例如,神经梅毒是一种外源性精神病,通过找到梅毒螺旋体的生物标志物,可以将神经梅毒这一新的疾病概念与精神分裂症区分开来)。由此可见,生物标志物研究对于精神疾病新诊断和治疗方法的开发至关重要。生物标志物研究方法有多种,如基因分析、生物样本分析、认知分析、神经生理学、神经影像学、动物模型以及尸检脑分析等。此外,虽然已经开展了多项研究,但尚未找到能够解释精神分裂症所有情况的生物标志物。由于精神分裂症被认为是一种异质性综合征,所以其病因被认为各不相同。因此,将精神分裂症作为一个整体来研究,有可能难以找到针对精神分裂症患者的生物标志物。人们认为需要进行适当的亚组分析。为了克服这一问题,欧美主要采用大量样本寻找患者的资源量策略。在日本,我们采用亚组分析策略来阐述这一问题,例如使用中间表型。由于与欧美相比,日本的资金和人力有限,无法研究类似策略。作为日本的全国性研究组织,如IGC(影像遗传学联盟),开展了遗传学与神经影像学的联合分析,以及COCORO(认知遗传学协作研究组织),开展了遗传学与认知功能的联合分析,预计在不久的将来精神疾病生物标志物将得到发展。

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