Immune mediated depressive behaviour: causes, consequences and therapeutic opportunities

抑郁症是致残程度最高的疾病之一，影响着全球3.4亿人。除了自发发生外，抑郁症状还经常与慢性免疫疾病有关，如炎症性风湿病、炎症性肠病、哮喘或传染病。一直以来，治疗诱导的外周免疫系统的激活可以导致抑郁行为的发展。这可以在使用重组干扰素(干扰素)-a治疗的丙型肝炎患者中观察到。因此，干扰素-a疗法为前瞻性地研究人类免疫介导的抑郁行为的机制提供了一个有希望的实验模型，我们计划在本研究中将其与干扰素-a诱导的抑郁行为的小鼠模型结合起来。根据我们的假设，抑郁行为是一种明确的外周免疫平衡失调的结果，导致错误的身体-大脑串扰。涉及的免疫介质可能包括细胞黏附分子、趋化因子/细胞因子和免疫耐受机制，如吲哚乙胺2，3-双加氧酶。本研究的目的是描述包含在这种错误的身体-大脑相声中的关键媒介。这些见解将提供对身体和精神之间的信号通路的深入了解，并随后将促进未来的研究，以提高治疗效率，不仅针对自发发生的抑郁症，而且针对慢性免疫疾病引发的抑郁行为。

Depression is one of the most disabling diseases, affecting 340 million people worldwide. Besides occuring spontaneously, depressive symptoms are frequently associated with chronic immunological diseases such as inflammatory rheumatic diseases, inflammatory bowel disease, asthma or infectious diseases. Consistently, a therapeutically induced activation of the peripheral immune system can lead to the development of a depressive behaviour. This can been observed e.g. in patients with hepatitis C upon treatment with recombinant interferon (IFN)-a. Thus, IFN-a therapy offers a promising experimental model for prospectively studying mechanisms of immune mediated depressive behaviour in humans, which we are planning to combine in the present study with a mouse model on IFN-a induced depressive behaviour. According to our hypothesis, depressive behaviour is the consequence of a defined peripheral immunological dysequilibrium, leading to an ill-routed body-brain cross talk. Immune mediators involved likely comprise cell adhesion molecules, chemokines/cytokines and mechanisms of immune tolerance, e.g. indoleamine 2,3- dioxygenase. The delineation of key mediators enclosed in this ill-routed body-brain cross talk is the aim of the present study. Such insights will provide an in depth understanding on signalling pathways between body and mind and will subsequently foster future research to improve therapeutical efficiency not only with respect to spontaneously occuring depression, but also depressive behaviour triggered by chronic immunological diseases.