Department of Psychiatry and Psychotherapy Ludwig Maximilian University and Marion von Tessin Memory Center, Munich, Germany.
Schizophr Bull. 2018 Aug 20;44(5):973-982. doi: 10.1093/schbul/sby024.
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.
本文讨论了目前来自动物和人类研究的证据，表明炎症在精神分裂症中起着核心作用。在动物模型中，产前或围产期引发免疫反应可能会增加整个生命周期的免疫反应性，并且在人类中也描述了类似的发现。已经发现，精神分裂症患者的血液和脑脊液中的促炎标志物（如细胞因子）水平升高。许多流行病学和临床研究提供了证据表明，各种感染因子是精神分裂症和其他精神病的危险因素。例如，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就是这种危险因素。易感性-应激-炎症模型可以帮助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炎的风险基因以及环境应激因素和免疫系统的改变。在低水平神经炎症中也发现了精神分裂症中描述的典型多巴胺能、5-羟色胺能、去甲肾上腺素能和谷氨酸能神经传递改变，因此可能是产生精神分裂症症状的关键因素。神经影像学研究中显示的中枢神经系统体积减少和小胶质细胞激活进一步支持了低水平神经炎症过程与精神分裂症的相关性。最后但并非最不重要的一点是，一些研究中发现抗炎药物的益处以及抗精神病药物的内在抗炎和免疫调节作用进一步支持了炎症在这种使人衰弱的疾病中的作用。
