Schmidt Mathias V, Sterlemann Vera, Müller Marianne B
Max Planck Institute of Psychiatry, Munich, Germany.
Ann N Y Acad Sci. 2008 Dec;1148:174-83. doi: 10.1196/annals.1410.017.
Over the last decades the burden of disease in Western countries has shifted from comparably easily treated infectious diseases to more complex diseases, such as the metabolic syndrome, cardiovascular disease, and psychiatric disorders. A common characteristic of these illnesses is the interplay of multiple genetic and nongenetic factors, which eventually results in the manifestation of disease symptoms. Large-scale epidemiological studies in humans have resulted in the identification of various environmental and genetic risk factors, which contribute to the onset, duration, and severity of disease. While tremendous progress has been made, it is still impossible to predict which combination of risk factors will result in the manifestation of a specific illness. This lack of knowledge is also frequently reflected in inadequate treatment strategies, which mainly focus on symptom reversal rather than targeting the cause of the diseases. One of the most prominent environmental risk factors described for numerous diseases is chronic exposure to stressful situations. In this paper we address clinical and preclinical evidence of chronic stress as a risk factor for disease and introduce a novel, high-throughput mouse model for chronic social stress. We can show that this model has a high degree of construct, face, and predictive validity in terms of physiological, behavioral, and gene expression changes. We further illustrate how novel animal models of chronic social stress can help to unravel the complex interaction of individual genetic vulnerability and environmental risk factors.
在过去几十年里，西方国家的疾病负担已从相对容易治疗的传染病转向更为复杂的疾病，如代谢综合征、心血管疾病和精神障碍。这些疾病的一个共同特征是多种遗传和非遗传因素的相互作用，最终导致疾病症状的显现。针对人类的大规模流行病学研究已确定了各种环境和遗传风险因素，这些因素会导致疾病的发生、持续时间和严重程度。尽管已经取得了巨大进展，但仍然无法预测哪些风险因素的组合会导致特定疾病的显现。这种知识的缺乏也常常反映在治疗策略的不足上，这些策略主要侧重于症状的缓解，而不是针对疾病的病因。众多疾病中描述的最突出的环境风险因素之一是长期暴露于压力情境。在本文中，我们阐述了慢性应激作为疾病风险因素的临床和临床前证据，并介绍了一种用于慢性社会应激的新型高通量小鼠模型。我们可以证明，该模型在生理、行为和基因表达变化方面具有高度的结构效度、表面效度和预测效度。我们进一步说明了慢性社会应激的新型动物模型如何有助于揭示个体遗传易感性与环境风险因素之间的复杂相互作用。
