Clinic for Affective Disorders & General Psychiatry, Psychiatric University Hospital Zurich, Switzerland.
Psychoneuroendocrinology. 2011 Apr;36(3):308-29. doi: 10.1016/j.psyneuen.2010.05.003. Epub 2010 Jun 9.
Depression presents as a disorder of feelings and thoughts that debilitate daily functioning and can be life threatening. Increased understanding of these specific emotional-cognitive pathological states and their underlying pathophysiologies and neuropathologies is fundamental to an increased understanding of the disorder and, therefore, to development of much-needed improved therapies. Despite this, there is a current lack of emphasis on development and application of translational (i.e. valid) neuropsychological measures in depression research. The appropriate strategy is neuropsychological research translated, bi-directionally, between epidemiological and clinical human research and in vivo - ex vivo preclinical research conducted, primarily, with mice. This paper presents a translational framework to stimulate and inform such research, in four inter-dependent sections. (1) A depression systems-model describes the pathway between human environment-gene (E-G) epidemiology, pathophysiology, psycho- and neuropathology, symptoms, and diagnosis. This model indicates that G→emotional-cognitive endophenotypes and E-G/endophenotype→emotional-cognitive state markers are central to experimental and translational depression research. (2) Human neuropsychological tests with (potential) translational value for the quantitative study of these endophenotypes and state markers are presented. (3) The analogous rodent behavioural tests are presented and their translational validity in terms of providing analogue emotional-cognitive endophenotypes and state markers are discussed. (4) The need for aetiological validity of mouse models in terms of G→endophenotypes and E-G→state markers is presented. We conclude that the informed application of the proposed neuropsychological translational framework will yield mouse models of high face, construct and aetiological validity with respect to emotional-cognitive dysfunction in depression. These models, together with the available technological tools, can then be studied to increase understanding of depression pathophysiology and neuropathology, leading to identification and validation of novel therapeutic targets and the development of effective, personalized antidepressant treatments.
抑郁症表现为一种影响情绪和思维的疾病，削弱日常功能，甚至可能危及生命。深入了解这些特定的情绪认知病理状态及其潜在的病理生理学和神经病理学，对于提高对该疾病的认识，从而开发急需的改进治疗方法至关重要。尽管如此，目前在抑郁症研究中，人们对转化（即有效）神经心理学测量方法的开发和应用重视不足。适当的策略是在流行病学和临床人类研究之间，以及主要在小鼠中进行的体内-体外临床前研究中，双向转化神经心理学研究。本文提出了一个转化框架，以促进和指导此类研究，分为四个相互依赖的部分。（1）抑郁症系统模型描述了人类环境-基因（E-G）流行病学、病理生理学、心理和神经病理学、症状和诊断之间的途径。该模型表明，G→情感认知内表型和 E-G/内表型→情感认知状态标志物对于实验和转化性抑郁症研究至关重要。（2）介绍了具有（潜在）转化价值的人类神经心理学测试，用于定量研究这些内表型和状态标志物。（3）介绍了类似的啮齿动物行为测试，并讨论了它们在提供情感认知内表型和状态标志物模拟方面的转化有效性。（4）提出了在 G→内表型和 E-G→状态标志物方面，需要对小鼠模型进行病因学有效性的研究。我们的结论是，明智地应用所提出的神经心理学转化框架将产生具有高表面、构建和病因学有效性的小鼠模型，以模拟抑郁症中的情绪认知功能障碍。这些模型，结合现有的技术工具，可以进一步研究，以增加对抑郁症病理生理学和神经病理学的理解，从而确定和验证新的治疗靶点，并开发有效的、个性化的抗抑郁治疗方法。
