Benros Michael E, Mortensen Preben B
Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
National Centre for Register Based Research, Aarhus University, Aarhus, Denmark.
Curr Top Behav Neurosci. 2020;44:141-159. doi: 10.1007/7854_2019_93.
An immunologic component to schizophrenia has been increasingly recognized, where infections and chronic inflammatory diseases as atopic disorders and autoimmune diseases could be involved in the pathogenesis of schizophrenia. Psychotic symptoms can be directly triggered by infections reaching the CNS, or be secondary to systemic inflammation indirectly affecting the brain through immune components, such as brain-reactive antibodies and cytokines. Large-scale epidemiological studies have consistently displayed that infections, autoimmune diseases, and atopic disorders are associated with increased risk of schizophrenia and that schizophrenia is associated with increased levels of immune markers at diagnosis. However, since there is also an increased risk of immune-related diseases after the diagnosis with schizophrenia and in family members of individuals with schizophrenia, parts of the association could also be due to heritable factors. Shared genetic factor might account for some of this increased prevalence of immune-related diseases among individuals with schizophrenia, and indeed the most pronounced genetic association with schizophrenia lies within the HLA region, which is one of the most important regions for the immune system. However, genetic studies have shown that the common genetic variants associated with schizophrenia do not seem to increase the susceptibility for acquiring infections. Nonetheless, shared genes with the susceptibility for acquiring infections not captured by the polygenic risk score for schizophrenia could still influence the association.
精神分裂症的免疫成分已越来越受到认可，其中感染以及诸如特应性疾病和自身免疫性疾病等慢性炎症性疾病可能参与了精神分裂症的发病机制。精神病性症状可由到达中枢神经系统的感染直接引发，或继发于通过免疫成分（如脑反应性抗体和细胞因子）间接影响大脑的全身性炎症。大规模流行病学研究一致表明，感染、自身免疫性疾病和特应性疾病与精神分裂症风险增加相关，且精神分裂症在诊断时与免疫标志物水平升高相关。然而，由于精神分裂症患者及其家庭成员在诊断后患免疫相关疾病的风险也会增加，部分关联也可能归因于遗传因素。共享的遗传因素可能是精神分裂症患者中免疫相关疾病患病率增加的部分原因，事实上，与精神分裂症最显著的基因关联位于HLA区域，该区域是免疫系统最重要的区域之一。然而，基因研究表明，与精神分裂症相关的常见基因变异似乎不会增加感染易感性。尽管如此，与感染易感性相关但未被精神分裂症多基因风险评分捕获的共享基因仍可能影响这种关联。
