Research Group of Psychoneuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.
Pharmacopsychiatry. 2011 May;44 Suppl 1:S15-26. doi: 10.1055/s-0031-1271702. Epub 2011 May 4.
Profound dysfunctions in several neuroendocrine systems have been described in patients suffering from affective disorders such as major depression. In order to elucidate the mechanisms underlying these functional alterations, animal models including mice genetically modified by either direct gene-targeting or by selective breeding approaches have been used exceedingly, revealing valuable insights into neuroendocrine pathways conserved between rodents and men. This review focuses on altered function and regulation of the hypothalamic-pituitary-adrenocortical axis, including its involvement in emotionality and stress responsiveness. In this context, the corticotropin-releasing hormone system and disturbances in glucocorticoid receptor signaling seem to be of central importance. However, changes in the expression and release patterns of vasopressin, dopamine and serotonin have also been shown to contribute to variation in emotionality, stress coping, cognitive functions and social behaviors. Affective disorders show a high degree of complexity, involving a multitude of molecular, neuroendocrine, and behavioral alterations as well as an intense gene-environment interaction, making it difficult to dissociate the primary causes from secondary consequences of the disease. Thus, interdisciplinary research, as applied in the emerging field of systems biology, involving adequate animal models and combined methodologies can significantly contribute to our understanding regarding the transmission of genetic predispositions into clinically relevant endophenotypes. It is only with deep insight into the mechanisms by which the stress hormone systems are regulated that novel treatment strategies and promising targets for therapeutic interventions can be developed in the future. Such in-depth understanding is ultimately essential to realizing our goal of predictive, preventive, and personalized medicine.
在患有情感障碍（如重度抑郁症）的患者中，已经描述了几个神经内分泌系统的深刻功能障碍。为了阐明这些功能改变的机制，已经使用了包括通过直接基因靶向或通过选择性繁殖方法遗传修饰的小鼠在内的动物模型，这些模型揭示了在啮齿动物和人类之间保守的神经内分泌途径的有价值的见解。
这篇综述重点介绍了下丘脑-垂体-肾上腺皮质轴的功能和调节改变，包括其在情感和应激反应中的作用。在这方面，促肾上腺皮质激素释放激素系统和糖皮质激素受体信号转导的紊乱似乎具有重要意义。然而，加压素、多巴胺和 5-羟色胺的表达和释放模式的变化也被证明有助于情感、应激应对、认知功能和社会行为的变化。
情感障碍表现出高度的复杂性，涉及多种分子、神经内分泌和行为改变以及强烈的基因-环境相互作用，使得很难将疾病的主要原因与次要后果区分开来。因此，跨学科研究，如应用于新兴的系统生物学领域，涉及适当的动物模型和综合方法，可以为我们理解遗传易感性如何转化为临床相关的表型提供重要贡献。只有深入了解应激激素系统调节的机制，才能在未来开发出新的治疗策略和有希望的治疗靶点。这种深入的了解对于实现我们的预测、预防和个性化医学的目标最终是至关重要的。
