The role of inflammation in schizophrenia.
The role of inflammation in schizophrenia.
复制标题
炎症在精神分裂症中的作用。
DOI：
10.3389/fnins.2015.00372
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发表时间：
2015
影响因子：
4.3
通讯作者：
Schwarz MJ
中科院分区：
文献类型：
--
作者：
Müller N;Weidinger E;Leitner B;Schwarz MJ
高水平的促炎物质，如细胞因子已被描述在精神分裂症患者的血液和脑脊液中。精神分裂症的动物模型表明，在某些条件下，生命早期的免疫紊乱，如感染引发的免疫激活，可能引发终身免疫反应性增加。一项大型流行病学研究清楚地表明，严重感染和自身免疫性疾病是精神分裂症的危险因素。遗传学研究表明，在染色体6p22.1上有一个强烈的精神分裂症信号，该区域与人类白细胞抗原（HLA）系统和其他免疫功能有关。另一系列证据表明，慢性（不适）压力与免疫激活有关。精神分裂症的易感性-应激-炎症模型包括基于遗传易感性增加的应激对精神分裂症发病机制的贡献，因为应激可能增加促炎细胞因子，甚至有助于持久的促炎状态。免疫改变影响多巴胺能、多巴胺能、去甲肾上腺素能和多巴胺能神经传递。激活的免疫系统进而激活色氨酸/犬尿氨酸代谢的吲哚胺2，3-双加氧酶（IDO），其通过神经活性代谢物如犬尿氨酸影响多巴胺能和多巴胺能神经传递。所描述的中枢神经系统体积的损失和小胶质细胞的激活，两者都已在精神分裂症患者的神经影像学研究中得到明确证明，与（低水平）炎症性神经毒性过程的假设相匹配。炎症假说的进一步支持来自抗炎药物的治疗益处。荟萃分析显示，环氧合酶-2抑制剂在精神分裂症的早期阶段具有有利的作用。此外，抗精神病药物的内在抗炎和免疫调节作用早已为人们所知。抗精神病药物的抗炎作用、抗炎化合物的治疗作用、遗传学、生物化学和免疫学研究结果表明，炎症在精神分裂症中起主要作用。
High levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA) system and other immune functions. Another line of evidence demonstrates that chronic (dis)stress is associated with immune activation. The vulnerability-stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis of schizophrenia, because stress may increase pro-inflammatory cytokines and even contribute to a lasting pro-inflammatory state. Immune alterations influence the dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission. The activated immune system in turn activates the enzyme indoleamine 2,3-dioxygenase (IDO) of the tryptophan/kynurenine metabolism which influences the serotonergic and glutamatergic neurotransmission via neuroactive metabolites such as kynurenic acid. The described loss of central nervous system volume and the activation of microglia, both of which have been clearly demonstrated in neuroimaging studies of schizophrenia patients, match the assumption of a (low level) inflammatory neurotoxic process. Further support for the inflammatory hypothesis comes from the therapeutic benefit of anti-inflammatory medication. Metaanalyses have shown an advantageous effect of cyclo-oxygenase-2 inhibitors in early stages of schizophrenia. Moreover, intrinsic anti-inflammatory, and immunomodulatory effects of antipsychotic drugs are known since a long time. Anti-inflammatory effects of antipsychotics, therapeutic effects of anti-inflammtory compounds, genetic, biochemical, and immunological findings point to a major role of inflammation in schizophrenia.