Accumulating evidence suggests that TNF-α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in a cross-sectional study that enrolled schizophrenia patients with (n = 40) and without (n = 40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial least squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-α and PON1 status (QQ genotype and lowered CMPAase activity), which lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-α and lowered IL-4, IgM to MDA, and education. In addition, both TNF-α and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-α was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.

中文翻译：

---

血浆肿瘤坏死因子-α 水平升高介导精神分裂症症状维度和神经认知障碍，并与针对丙二醛和对氧磷酶 1 活性的天然 IgM 呈负相关。

越来越多的证据表明，TNF-α 介导的免疫神经毒性会导致认知障碍和精神分裂症 (OSOS) 的整体严重程度。没有数据表明外周血 IL-6 和 IL-4 是否会在 TNF-α 的影响之外影响精神分裂症的表型，以及这些细胞因子是否受降低的天然 IgM 对丙二醛 (MDA) 和对氧磷酶 1 酶活性的调节。我们在一项横断面研究中评估了上述生物标志物，该研究招募了患有 (n = 40) 和没有 (n = 40) 缺陷型精神分裂症的精神分裂症患者和 40 名健康对照。缺陷型精神分裂症最好通过 IL-6 和 PON1 状态增加（QQ 基因型和 CMPAase 活性降低）和 IgM 降低到 MDA 的组合来预测。偏最小二乘法表明阴性症状的方差有 41.0%，TNF-α 和 PON1 状态（QQ 基因型和 CMPAase 活性降低）的增加解释了精神病、敌意、兴奋、行为习惯、精神运动迟缓和形式思维障碍，这降低了 MDA 的 IL-4 和 IgM 以及男性和降低教育。我们发现 47.9% 的语言流利度、单词列表记忆、真实回忆、简易精神状态检查和执行功能的变化可以通过 TNF-α 增加和 IL-4、IgM 到 MDA 和教育程度降低来预测。此外，TNF-α 和 IL-4 水平均与 IgM 对 MDA 的降低显着相关，而 TNF-α 与 PON1 状态相关。