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人类焦虑障碍的动物模型:从发展心理病理学的角度重新评价。

Animal models of human anxiety disorders: reappraisal from a developmental psychopathology vantage point.

机构信息

Academic Centre for Study of Behavioral Plasticity, Vita-Salute San Raffaele University, 20127 Milan, Italy.

出版信息

Pediatr Res. 2011 May;69(5 Pt 2):77R-84R. doi: 10.1203/PDR.0b013e318212b42e.

Abstract

We are witnessing a tremendous expansion of strategies and techniques that derive from basic and preclinical science to study the fine genetic, epigenetic, and proteomic regulation of behavior in the laboratory animal. In this endeavor, animal models of psychiatric illness are becoming the almost exclusive domain of basic researchers, with lesser involvement of clinician researchers in their conceptual design, and transfer into practice of new paradigms. From the side of human behavioral research, the growing interest in gene-environment interplay and the fostering of valid endophenotypes are among the few substantial innovations in the effort of linking common mental disorders to cutting-edge clinical research questions. We argue that it is time for cross-fertilization between these camps. In this article, we a) observe that the "translational divide" can-and should-be crossed by having investigators from both the basic and the clinical sides cowork on simpler, valid "endophenotypes" of neurodevelopmental relevance; b) emphasize the importance of unambiguous physiological readouts, more than behavioral equivalents of human symptoms/syndromes, for animal research; c) indicate and discuss how this could be fostered and implemented in a developmental framework of reference for some common anxiety disorders and ultimately lead to better animal models of human mental disorders.

摘要

我们正目睹着源自基础和临床前科学的策略和技术的巨大扩展,这些策略和技术旨在研究实验室动物行为的精细遗传、表观遗传和蛋白质组学调控。在这一努力中,精神疾病的动物模型几乎成为了基础研究人员的专属领域,临床研究人员较少参与其概念设计,也较少将新范式转化为实践。从人类行为研究的角度来看,对基因-环境相互作用的日益关注以及有效内表型的培养是将常见精神障碍与前沿临床研究问题联系起来的少数实质性创新之一。我们认为,现在是这些阵营之间交叉授粉的时候了。在本文中,我们:a)观察到,通过让基础和临床研究人员共同研究更简单、有效的神经发育相关性“内表型”,“转化鸿沟”是可以而且应该被跨越的;b)强调对于动物研究来说,明确的生理读数比人类症状/综合征的行为等效物更重要;c)指出并讨论如何在一些常见焦虑障碍的发展参考框架中促进和实施这一点,最终导致更好的人类精神障碍动物模型。

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