Role of Brain Imaging in Drug Development for Psychiatry.

J. D. den Boer, E. D. de Vries, R. Borra, A. Waarde, A. Lammertsma, R. Dierckx
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Abstract

BACKGROUND Over the last decades, many brain imaging studies have contributed to new insights in the pathogenesis of psychiatric disease. However, in spite of these developments, progress in the development of novel therapeutic drugs for prevalent psychiatric health conditions has been limited. OBJECTIVE In this review, we discuss translational, diagnostic and methodological issues that have hampered drug development in CNS disorders with a particular focus on psychiatry. The role of preclinical models is critically reviewed and opportunities for brain imaging in early stages of drug development using PET and fMRI are discussed. The role of PET and fMRI in drug development is reviewed emphasizing the need to engage in collaborations between industry, academia and phase I units. RESULTS Brain imaging technology has revolutionized the study of psychiatric illnesses, and during the last decade, neuroimaging has provided valuable insights at different levels of analysis and brain organization, such as effective connectivity (anatomical), functional connectivity patterns and neurochemical information that may support both preclinical and clinical drug development. CONCLUSION Since there is no unifying pathophysiological theory of individual psychiatric syndromes and since many symptoms cut across diagnostic boundaries, a new theoretical framework has been proposed that may help in defining new targets for treatment and thus enhance drug development in CNS diseases. In addition, it is argued that new proposals for data-mining and mathematical modelling as well as freely available databanks for neural network and neurochemical models of rodents combined with revised psychiatric classification will lead to new validated targets for drug development.
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脑成像在精神病学药物开发中的作用。
背景在过去的几十年里,许多脑成像研究为精神疾病的发病机制提供了新的见解。然而,尽管取得了这些进展,但针对普遍存在的精神健康状况的新型治疗药物的开发进展有限。目的在这篇综述中,我们讨论了阻碍中枢神经系统疾病药物开发的转化、诊断和方法学问题,特别关注精神病学。对临床前模型的作用进行了批判性的回顾,并讨论了使用PET和fMRI进行大脑成像在药物开发早期阶段的机会。回顾了PET和fMRI在药物开发中的作用,强调了参与工业界、学术界和第一阶段单位之间合作的必要性。结果脑成像技术彻底改变了精神疾病的研究,在过去的十年里,神经成像在不同层次的分析和大脑组织方面提供了有价值的见解,如有效连接(解剖学)、功能连接模式和神经化学信息,这些信息可能支持临床前和临床药物开发。结论由于个体精神综合征没有统一的病理生理学理论,而且许多症状跨越了诊断界限,因此提出了一个新的理论框架,这可能有助于确定新的治疗靶点,从而促进中枢神经系统疾病的药物开发。此外,有人认为,数据挖掘和数学建模的新提议,以及啮齿动物神经网络和神经化学模型的免费数据库,再加上修订的精神分类,将为药物开发带来新的验证目标。
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来源期刊
CiteScore
4.80
自引率
9.10%
发文量
55
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