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神经精神疾病药物发现中的研究领域标准框架:聚焦负性情绪。

The research domain criteria framework in drug discovery for neuropsychiatric diseases: focus on negative valence.

作者信息

Nicholson Janet R, Sommer Bernd

机构信息

CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.

出版信息

Brain Neurosci Adv. 2018 Nov 7;2:2398212818804030. doi: 10.1177/2398212818804030. eCollection 2018 Jan-Dec.

Abstract

Drug discovery, particularly in the field of central nervous system, has had very limited success in the last few decades. A likely contributor is the poor translation between preclinical and clinical phases. The Research Domain Criteria of the National Institutes of Mental Health is a framework which aims to identify new ways of classifying mental illnesses that are based on observable behaviour and neurobiological measures, and to provide a guiding and evolving framework to improve the translation from preclinical to clinical research. At the core of the Research Domain Criteria approach is the assumption that the dimensional constructs described can be assessed across different units of analysis, thus enabling a more precise quantitative understanding of their neurobiological underpinnings, increasing the likelihood of identifying new and effective therapeutic approaches. In the present review, we discuss how the Research Domain Criteria can be applied to drug discovery with the domain Negative Valence, construct Potential Threat ('Anxiety') as an example. We will discuss the evidence supporting the utility of the Research Domain Criteria approach and evaluate how close we are to achieving a common thread of translational research from gene to self-report.

摘要

在过去几十年里,药物研发,尤其是在中枢神经系统领域,取得的成功非常有限。一个可能的原因是临床前阶段和临床阶段之间的转化效果不佳。美国国立精神卫生研究所的研究领域标准是一个框架,旨在确定基于可观察行为和神经生物学指标对精神疾病进行分类的新方法,并提供一个指导性的、不断发展的框架,以改善从临床前研究到临床研究的转化。研究领域标准方法的核心假设是,所描述的维度结构可以在不同的分析单元中进行评估,从而能够更精确地定量理解其神经生物学基础,增加识别新的有效治疗方法的可能性。在本综述中,我们以负性效价领域、潜在威胁(“焦虑”)结构为例,讨论研究领域标准如何应用于药物研发。我们将讨论支持研究领域标准方法实用性的证据,并评估我们距离实现从基因到自我报告的转化研究的共同主线还有多远。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d1/7058263/736e9cd6611d/10.1177_2398212818804030-fig1.jpg

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