Denis Goetghebeur Pascal Jean, Dias Rebecca
Takeda Cambridge Ltd, 418 Cambridge science park, Cambridge CB4 0PA, UK.
Curr Pharm Des. 2014;20(31):5060-8. doi: 10.2174/1381612819666131216114909.
Cognition deficits in schizophrenia remain an untreated area, and one in which R&D investment by pharmaceutical companies is high. However, whilst many preclinical assays demonstrate pro-cognitive activity with new drugs, in the main, they have not yet been translated successfully to the clinic. In an attempt to address this and reduce the high attrition rate for drugs in the clinic, selected preclinical researchers are re-focusing their efforts on the development and validation of more translational assays. The attentional setshifting task is an example of such an assay, which has been back-translated from the clinic to a preclinical setting. Here we review its application in schizophrenia research across humans and animals, specifically with regards to the neural basis underlying cognitive performance, the various disease-like or symptom models employed in rodents to mimic cognitive dysfunction in schizophrenia, and the resulting impact of drug treatment on executive function. Using the attentional set-shifting task, we highlight the potential promise a more translational approach can bring, whilst demonstrating the need for closer alignment in the validation and integration of this task to fully realize this promise.
精神分裂症的认知缺陷仍是一个未得到治疗的领域，也是制药公司研发投资较高的领域。然而，尽管许多临床前试验表明新药具有促认知活性，但总体而言，它们尚未成功转化至临床。为了解决这一问题并降低药物在临床中的高淘汰率，部分临床前研究人员正将工作重点重新放在开发和验证更具转化性的试验上。注意力转换任务就是这样一种试验的例子，它已从临床反向转化至临床前环境。在此，我们回顾其在人类和动物精神分裂症研究中的应用，特别是关于认知表现背后的神经基础、啮齿动物中用于模拟精神分裂症认知功能障碍的各种疾病样或症状模型，以及药物治疗对执行功能的影响。通过注意力转换任务，我们强调了更具转化性的方法可能带来的潜在前景，同时表明需要在该任务的验证和整合方面更紧密地结合，以充分实现这一前景。
