Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise selection procedure. Broad screening and follow-up targeted analyses revealed highly individual autoantibody profiles. Females, and people with family histories of obesity or of psychiatric disorders other than schizophrenia had the highest overall autoantibody counts. People who had experienced subjective thought disorder and/or were treated with clozapine (trend) had the lowest overall counts. Furthermore, six autoantibodies were associated with specific psychopathology symptoms: anti-AP3B2 (persecutory delusions), anti-TDO2 (hallucinations), anti-CRYGN (initial insomnia); anti-APMAP (poor appetite), anti-OLFM1 (above-median cognitive function), and anti-WHAMMP3 (anhedonia and dysphoria). Future studies should clarify whether there are causal biological relationships, and whether autoantibodies could be used as clinical markers to inform diagnostic patient stratification and choice of treatment.

怀疑自身免疫过程在精神病的病理生理学中起作用。更好地了解自身免疫球蛋白 G (IgG) 库与精神疾病临床特征之间的关联，可以产生精神病病理生理学的新模型，以及生物学患者分层的标志物。我们对 461 名确诊为精神病的人（39% 女性）的外周血浆中的自身 IgG 进行了横断面检测和定量。使用包含代表 18,914 种蛋白质的 42,100 个人类抗原的平面蛋白质微阵列，在八个临床定义的组中对 24 个人进行了广泛的筛查。广泛筛选和先前文献中显示的自身抗体是使用基于 380 重珠的阵列测量的，用于对所有 461 个个体进行自身抗体分析。使用逐步选择程序评估自身抗体谱和二分临床特征之间的关联。广泛的筛选和后续靶向分析揭示了高度个体化的自身抗体谱。女性和有肥胖或精神分裂症以外的精神疾病家族史的人的总体自身抗体计数最高。经历过主观思维障碍和/或接受氯氮平治疗（趋势）的人的总计数最低。此外，六种自身抗体与特定的精神病理学症状相关：抗 AP3B2（被害妄想）、抗 TDO2（幻觉）、抗 CRYGN（初始失眠）；抗 APMAP（食欲不振）、抗 OLFM1（高于中位数认知功能）和抗 WHAMMP3（快感缺失和烦躁不安）。未来的研究应阐明是否存在因果生物学关系，以及自身抗体是否可用作临床标志物，为诊断患者分层和治疗选择提供信息。