Immune mediated depressive behaviour: causes, consequences and therapeutic opportunities

抑郁症是最致残的疾病之一，影响着全世界3.4亿人。抑郁症状除了自发发生外，还经常与慢性免疫性疾病有关，如炎症性风湿病、炎症性肠病、哮喘或传染病。一贯地，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。这可以在丙型肝炎患者用重组干扰素(IFN)-a治疗后观察到。因此，IFN-a疗法为前瞻性研究免疫介导的人类抑郁行为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IFN-a诱导的抑郁行为小鼠模型结合起来。根据我们的假设，抑郁行为是一种明确的外周免疫失衡的结果，导致了一种路由不佳的身体-大脑串音。涉及的免疫介质可能包括细胞粘附分子、趋化因子/细胞因子和免疫耐受机制，例如吲哚胺2,3-双加氧酶。在这种不正常的身体-大脑串音中所包含的关键介质的描述是本研究的目的。这些见解将提供对身体和心灵之间信号传导途径的深入理解，并将随后促进未来的研究，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.