Clinical studies of neuroinflammatory mechanisms in schizophrenia
Clinical studies of neuroinflammatory mechanisms in schizophrenia
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DOI：
10.1016/j.schres.2015.07.018
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发表时间：
2016-09
影响因子：
4.5
通讯作者：
C. Watkins;S. Andrews
中科院分区：
文献类型：
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作者：
C. Watkins;S. Andrews
精神分裂症是一种普遍的神经发育障碍，似乎是由遗传和环境因素引起的。虽然多巴胺假说是精神分裂症中大多数翻译研究背后的驱动理论，但新出现的证据表明，外周和中枢神经系统中的异常免疫机制影响精神分裂症的病因学和定义疾病的精神病症状的病理生理学。对炎症过程的最初兴趣来自流行病学数据和历史观察，可以追溯到几十年前。越来越多的关于发育暴露于感染、应激诱导的炎症反应、神经胶质细胞信号传导、结构和功能性大脑变化以及治疗试验的研究表明，炎症对精神分裂症的发作和进展有影响。对精神病动物模型的研究有助于推进对精神分裂症免疫机制破坏的临床和基础科学研究。然而，它们受到无法概括人类幻觉、妄想和思维障碍的限制，这些都是精神病的定义。迄今为止，人类受试者的炎症机制的翻译研究尚未进行详细综述。在这里，我们批判性地回顾了精神分裂症炎症机制的临床研究。了解精神分裂症中涉及的神经炎症机制对于确定潜在的治疗靶点以通过中断疾病发展来最小化精神分裂症的发病率和死亡率可能是至关重要的。
Schizophrenia is a pervasive neurodevelopmental disorder that appears to result from genetic and environmental factors. Although the dopamine hypothesis is the driving theory behind the majority of translation research in schizophrenia, emerging evidence suggests that aberrant immune mechanisms in the peripheral and central nervous system influence the etiology of schizophrenia and the pathophysiology of psychotic symptoms that define the illness. The initial interest in inflammatory processes comes from epidemiological data and historical observations, dating back several decades. A growing body of research on developmental exposure to infection, stress-induced inflammatory response, glial cell signaling, structural and functional brain changes and therapeutic trials demonstrates the impact that inflammation has on the onset and progression of schizophrenia. Research in animal models of psychosis has helped to advance clinical and basic science investigations of the immune mechanisms disrupted in schizophrenia. However, they are limited by the inability to recapitulate the human experience of hallucinations, delusions and thought disorder that define psychosis. To date, translational studies of inflammatory mechanisms in human subjects have not been reviewed in great detail. Here, we critically review clinical studies that focus on inflammatory mechanisms in schizophrenia. Understanding the neuroinflammatory mechanisms involved in schizophrenia may be essential in identifying potential therapeutic targets to minimize the morbidity and mortality of schizophrenia by interrupting disease development.