Department of Neuroscience, Physiology and Pharmacology, 4919University College London, London, UK.
Altern Lab Anim. 2020 May;48(3):106-115. doi: 10.1177/0261192920939876. Epub 2020 Aug 10.
The repeated failure of animal models to yield findings that translate into humans is a serious threat to the credibility of preclinical biomedical research. The use of animals in research that lacks translational validity is unacceptable in any ethical environment, and so this problem needs urgent attention. To reproduce any human illness in animals is a serious challenge, but this is especially the case for psychiatric disorders. Yet, many authors do not hesitate to describe their findings as a 'model' of such a disorder. More cautious scientists describe the behavioural phenotype as 'disorder-like', without specifying the way(s) in which the abnormal behaviour could be regarded as being analogous to any of the diagnostic features of the disorder in question. By way of discussing these problems, this article focuses on common, but flawed, assumptions that pervade preclinical research of depression and antidepressants. Particular attention is given to the difference between putative 'models' of this illness and predictive screens for candidate drug treatments, which is evidently widely misunderstood. However, the problems highlighted in this article are generic and afflict research of all psychiatric disorders. This dire situation will be resolved only when funders and journal editors take action to ensure that researchers interpret their findings in a less ambitious, but more realistic, evidence-based way that would parallel changes in research of the cause(s), diagnosis and treatment of psychiatric problems in humans.
动物模型的研究结果无法在人类身上得到验证，这对临床前生物医学研究的可信度构成了严重威胁。在任何伦理环境下，缺乏转化有效性的动物研究都是不可接受的，因此这个问题需要引起紧急关注。在动物身上重现任何人类疾病都是一个严峻的挑战，但精神疾病尤其如此。然而，许多作者毫不犹豫地将他们的发现描述为这种疾病的“模型”。更谨慎的科学家将行为表型描述为“类似疾病”，而没有具体说明异常行为可以被视为与所讨论疾病的任何诊断特征有何相似之处。本文通过讨论这些问题，重点关注了弥漫在抑郁症和抗抑郁药临床前研究中的常见但有缺陷的假设。特别关注了这种疾病的假定“模型”与候选药物治疗的预测性筛选之间的区别，这显然被广泛误解了。然而，本文强调的问题是普遍存在的，并困扰着所有精神疾病的研究。只有当资助者和期刊编辑采取行动，确保研究人员以一种不那么雄心勃勃、但更现实的基于证据的方式解释他们的发现时，这种严峻的局面才会得到解决，这种方式将与人类精神问题的病因、诊断和治疗研究的变化相平行。
