Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations
Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations
复制标题
DOI：
10.1093/schbul/sby024
复制
发表时间：
2018-09-01
影响因子：
6.6
通讯作者：
Mueller, Norbert
中科院分区：
文献类型：
--
作者：
Mueller, Norbert
本文讨论了目前来自动物和人类研究的证据，证明炎症在精神分裂症中起着核心作用。在动物模型中，产前或围产期免疫反应的激发可能会增加一生中的免疫反应性，人类也有类似的发现。精神分裂症患者血液和脑脊液中的促炎标志物水平，如细胞因子，已被发现增加。大量的流行病学和临床研究表明，各种感染源是精神分裂症和其他精神病的危险因素。例如，在丹麦进行的一项大规模流行病学研究清楚地表明，严重感染和自身免疫性疾病是此类危险因素。脆弱性-应激-炎症模型可能有助于解释炎症在精神分裂症中的作用，因为应激可以增加促炎细胞因子，甚至可能导致慢性促炎状态。精神分裂症的特征是促进炎症的危险基因，以及环境应激因素和免疫系统的变化。精神分裂症中典型的多巴胺能、5-羟色胺能、去甲肾上腺素和谷氨酸能神经传递的改变也在低水平的神经炎症中被发现，因此可能是精神分裂症症状产生的关键因素。神经成像研究表明，中枢神经系统体积的丧失和小胶质细胞的激活进一步支持了精神分裂症与低水平神经炎过程的相关性。最后但并非最不重要的一点是，一些研究中发现的抗炎药物的益处，以及抗精神病药物固有的抗炎和免疫调节作用，进一步支持了炎症在这种衰弱疾病中的作用。
This paper discusses the current evidence from animal and human studies for a central role of inflammation in schizophrenia. In animal models, pre- or perinatal elicitation of the immune response may increase immune reactivity throughout life, and similar findings have been described in humans. Levels of pro-inflammatory markers, such as cytokines, have been found to be increased in the blood and cerebrospinal fluid of patients with schizophrenia. Numerous epidemiological and clinical studies have provided evidence that various infectious agents are risk factors for schizophrenia and other psychoses. For example, a large-scale epidemiological study performed in Denmark clearly showed that severe infections and autoimmune disorders are such risk factors. The vulnerability-stress-inflammation model may help to explain the role of inflammation in schizophrenia because stress can increase pro-inflammatory cytokines and may even contribute to a chronic pro-inflammatory state. Schizophrenia is characterized by risk genes that promote inflammation and by environmental stress factors and alterations of the immune system. Typical alterations of dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission described in schizophrenia have also been found in low-level neuroinflammation and consequently may be key factors in the generation of schizophrenia symptoms. Further support for the relevance of a low-level neuroinflammatory process in schizophrenia is provided by the loss of central nervous system volume and microglial activation demonstrated in neuroimaging studies. Last but not least, the benefit of anti-inflammatory medications found in some studies and the intrinsic anti-inflammatory and immunomodulatory effects of antipsychotics provide further support for the role of inflammation in this debilitating disease.