Pryce Christopher R, Rüedi-Bettschen Daniela, Dettling Andrea C, Weston Anna, Russig Holger, Ferger Boris, Feldon Joram
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Zurich, Switzerland.
Neurosci Biobehav Rev. 2005;29(4-5):649-74. doi: 10.1016/j.neubiorev.2005.03.011. Epub 2005 Apr 25.
Depression is one of the most common human illnesses and is of immense clinical and economic significance. Knowledge of the neuro-psychology, -biology and -pharmacology of depression is limited, as is the efficacy of antidepressant treatment. In terms of depression aetiology, whilst the evidence for causal mechanisms is sparse, some genomic and environmental factors associated with increased vulnerability have been identified. With regards to the latter, the environments in which human infants and children develop are fundamental to how they develop, and parental loss, emotional and physical neglect, and abuse have been shown to be associated with: traits of depression, traits of predisposition to depression triggered by subsequent life events, and associated physiological abnormalities, across the life span. Studies of postnatal environmental manipulations in rodents and primates can potentially yield evidence that abnormal early-life experience leading to dysfunction of the neurobiology, physiology and behaviour of emotion is a general mammalian characteristic, and therefore, that this approach can be used to develop animal models for depression research, with aetiological, face, construct and predictive validity. The establishment of models with such validity, if at all achievable, will require a sophisticated combination of (1) appropriate postnatal manipulations that induce acute stress responses in the infant brain which in turn lead to long-term neurobiological consequences, and (2) appropriate behavioural and physiological assays to identify and quantify any depression-like phenotypes resulting from these long-term neurobiological phenotypes. Here, we review some of the evidence-positive and negative-that neglect-like environments in rat pups and monkey infants lead to long-term, depression-like behavioural traits of reduced motivation for reward and impaired coping with adversity, and to altered activity in relevant physiological homeostatic systems.
抑郁症是人类最常见的疾病之一，具有重大的临床和经济意义。关于抑郁症的神经心理学、神经生物学和神经药理学的知识有限，抗抑郁治疗的疗效也同样有限。在抑郁症病因方面，虽然因果机制的证据稀少，但已确定了一些与易感性增加相关的基因组和环境因素。就后者而言，人类婴幼儿成长的环境对其发育方式至关重要，研究表明，父母离世、情感和身体上的忽视以及虐待与以下情况相关：抑郁症特征、后续生活事件引发的抑郁症易感性特征，以及一生中相关的生理异常。对啮齿动物和灵长类动物出生后环境操纵的研究有可能提供证据，证明导致情绪神经生物学、生理学和行为功能障碍的异常早期生活经历是哺乳动物的普遍特征，因此，这种方法可用于开发抑郁症研究的动物模型，具有病因学、表面、结构和预测效度。要建立具有这种效度的模型（如果确实可行的话），将需要复杂地结合：（1）适当的出生后操纵，在幼小动物大脑中诱发急性应激反应，进而导致长期的神经生物学后果；（2）适当的行为和生理测定，以识别和量化这些长期神经生物学表型所产生的任何类似抑郁症的表型。在此，我们回顾一些证据——既有正面的也有负面的——即大鼠幼崽和猕猴幼崽所处的类似忽视的环境会导致长期的、类似抑郁症的行为特征，如奖励动机降低和应对逆境能力受损，以及相关生理稳态系统的活动改变。
