Icahn School of Medicine at Mount Sinai, Department of Psychiatry, New York, NY, United States of America.
Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, United States of America; Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, United States of America; Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD, United States of America; Johns Hopkins University School of Medicine, Institute of Genomics Medicine, Baltimore, MD, United States of America; Johns Hopkins University School of Medicine, Department of Neuroscience, Baltimore, MD, United States of America.
Schizophr Res. 2020 Mar;217:105-113. doi: 10.1016/j.schres.2019.02.005. Epub 2019 Mar 5.
The immune system has long been hypothesized to play a role in schizophrenia pathogenesis based on data from diverse disciplines. Recent reports of the identification of schizophrenia-associated genetic variants and their initial biological characterization have renewed investigation of the role of the immune system in schizophrenia. In the current review, the plausibility of a role of the immune system in schizophrenia pathogenesis is examined, by revisiting epidemiology, neuroimaging, pharmacology, and developmental biology from a genetics perspective, as well as by synthesizing diverse findings from the emerging and dynamic schizophrenia genomics field. Genetic correlations between schizophrenia and immunological disorders are inconsistent and often contradictory, as are neuroimaging studies of microglia markers. Small therapeutic trials of anti-inflammatory agents targeting immune function have been consistently negative. Some gene expression analyses of post-mortem brains of patients with schizophrenia have reported an upregulation of genes of immune function though others report downregulation, and overall transcriptome profiling to date does not support an upregulation of immune pathways associated with schizophrenia genetic risk. The currently reviewed genetic data do not converge to reveal consistent evidence of the neuroimmune system in schizophrenia pathogenesis, and indeed, a substantive role for the neuroimmune system in schizophrenia has yet to be established.
基于来自不同学科的数据，免疫系统在精神分裂症发病机制中发挥作用的假说由来已久。最近报道的与精神分裂症相关的遗传变异的鉴定及其初步生物学特征，重新引发了对免疫系统在精神分裂症中的作用的研究。在当前的综述中，通过从遗传学角度重新审视流行病学、神经影像学、药理学和发育生物学，以及综合新兴和动态的精神分裂症基因组学领域的各种发现，检查了免疫系统在精神分裂症发病机制中的作用的可能性。精神分裂症和免疫性疾病之间的遗传相关性不一致且常常相互矛盾，神经影像学中小胶质细胞标志物的研究也是如此。针对免疫功能的抗炎药物的小型治疗试验一直是阴性的。一些精神分裂症患者死后大脑的基因表达分析报告了免疫功能基因的上调，而另一些报告则下调，迄今为止，总体转录组谱分析并不支持与精神分裂症遗传风险相关的免疫途径的上调。目前综述的遗传数据并未汇聚，以揭示精神分裂症发病机制中神经免疫系统的一致证据，事实上，神经免疫系统在精神分裂症中的实质性作用尚未得到确立。
