Laboratory of Mosaic of Autoimmunity, Saint-Peterburg State University, Department of Psychiatry and Addiction, Saint-Petersburg, Russia,
Psychiatr Danub. 2021 Spring;33(1):3-17. doi: 10.24869/psyd.2021.3.
The review analyzes the possible role of autoimmune processes in the pathogenesis of schizophrenia and the evolution of concepts on this issue from its origin to the present.
Risks of autoimmune processes causing schizophrenia are associated with several factors: an impaired functioning of dopaminergic and glutamatergic systems in the brain, kynurenine pathway disorder with overproduction of quinolinic, anthranilic, and kynurenic acids (possibly altering both neurons and T-regulators), increased intestinal permeability, as well as food antigens' effects, stress and infections with various pathogens at different stages of ontogenesis. An increase in the levels of proinflammatory cytokines and chemokines as well as a decrease in the levels of anti-inflammatory ones also may contribute to schizophrenia risks. Schizophrenia often occurs in those patients having various autoimmune diseases and their first-degree relatives.
Cases of schizophrenia resulted from autoimmune pathogenesis (including autoimmune encephalitis caused by autoantibodies against various neuronal antigens) are characterized by quite severe cognitive and psychotic symptoms and a less favorable prognosis. This severe course may result from the chronic immune damage of the neuronal receptors such as NMDA, GABA, and others and depend on hyperprolactinemia, induced by antipsychotics, but aggravating autoimmune processes.
本文综述分析了自身免疫过程在精神分裂症发病机制中的可能作用，以及该问题概念的演变，从其起源到现在。
自身免疫过程导致精神分裂症的风险与几个因素有关：大脑中多巴胺能和谷氨酸能系统功能障碍，犬尿氨酸途径紊乱导致喹啉酸、邻氨基苯甲酸和犬尿氨酸过量产生（可能同时改变神经元和 T 调节细胞），肠通透性增加，以及食物抗原的作用、应激和各种病原体在不同发育阶段的感染。促炎细胞因子和趋化因子水平的升高以及抗炎因子水平的降低也可能导致精神分裂症的风险增加。精神分裂症常发生于患有各种自身免疫性疾病的患者及其一级亲属中。
由自身免疫发病机制引起的精神分裂症病例（包括自身抗体引起的各种神经元抗原自身免疫性脑炎）的特点是认知和精神病症状相当严重，预后较差。这种严重的病程可能是由于 NMDA、GABA 等神经元受体的慢性免疫损伤引起的，并且依赖于抗精神病药物引起的催乳素水平升高，但会加重自身免疫过程。
