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评估啮齿动物、非人灵长类动物和人类的行为与认知:翻译的局限性在哪里?

Assessing behavior and cognition in rodents, nonhuman primates, and humans: where are the limits of translation?
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作者信息

Stephan Marius, Volkmann Paul, Rossner Moritz J

机构信息

Molecular and Behavioural Neurobiology, Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany.

Molecular and Behavioural Neurobiology, Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Germany.

出版信息

Dialogues Clin Neurosci. 2019 Sep;21(3):249-259. doi: 10.31887/DCNS.2019.21.3/mrossner.

Abstract

New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier developments mostly failed, probably partly because of limitations in behavioral models used for validation. Now, deeper understanding of the genetics underlying disease pathogenesis and progress in genetic engineering will generate many rodent models with increased construct validity. To improve these models' translational value, we need complementary data from nonhuman primates. We also have to improve and streamline behavioral test systems to cope with increased demand. Here, we propose a comprehensive neurocognitive test battery that should overcome the disadvantages of single tests and yield cognitive/behavioral profiles for modeling subsets of patient symptoms. Further, we delineate a concept for classifying disease-relevant cognitive endophenotypes to balance between face and construct validity and clinical diagnostics. In summary, this review discusses new concepts and the limitations and future potential of translational research on cognition in psychiatry.
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摘要

情感性和非情感性精神病需要新的精神药理学治疗方法,尤其是针对相关的阴性和认知症状。早期的进展大多失败了,可能部分原因是用于验证的行为模型存在局限性。现在,对疾病发病机制背后遗传学的更深入理解以及基因工程的进展将产生许多构建效度更高的啮齿动物模型。为了提高这些模型的转化价值,我们需要来自非人类灵长类动物的补充数据。我们还必须改进和简化行为测试系统以应对不断增加的需求。在此,我们提出了一套全面的神经认知测试组合,该组合应克服单一测试的缺点,并为模拟患者症状子集产生认知/行为概况。此外,我们描绘了一个对与疾病相关的认知内表型进行分类的概念,以在表面效度和构建效度以及临床诊断之间取得平衡。总之,本综述讨论了精神病学认知转化研究的新概念、局限性和未来潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a27/6829167/6c7abab91f35/DCNS_21.3_fig1_Rossner.jpg

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