Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Mol Neurobiol. 2018 Mar;55(3):2214-2226. doi: 10.1007/s12035-017-0465-y. Epub 2017 Mar 14.
Deficit schizophrenia is accompanied by mucosa-associated activation of the tryptophan catabolite (TRYCAT) pathway, as indicated by increased IgA responses to noxious (NOX) TRYCATs, but not regulatory or protective (PRO) TRYCATs, suggesting increased neurotoxic, excitotoxic, inflammatory, and oxidative potential. No previous studies examined IgM-mediated autoimmune responses to the TRYCAT pathway in deficit versus nondeficit schizophrenia. We measured IgM responses to NOX TRYCATs, namely, quinolinic acid (QA), 3-OH-kynurenine (3HK), picolinic acid (PA), and xanthurenic (XA) acid, and PRO TRYCATs, including kynurenic acid (KA) and anthranilic acid (AA), in 40 healthy controls and 40 deficit and 40 nondeficit schizophrenic patients. We computed the IgM responses to NOX (QA + PA + 3HK + XA)/PRO (AA + KA) ratio and ∆ differences in IgA - IgM TRYCAT values and NOX/PRO ratio. Deficit schizophrenia is characterized by significantly attenuated IgM responses to all TRYCATs and NOX/PRO ratio and highly increased ∆IgA - IgM NOX/PRO ratio as compared to nondeficit schizophrenia and healthy controls. The negative symptoms of schizophrenia are significantly and positively associated with increased IgM responses directed against the KA/3HK ratio and ∆IgA - IgM NOX/PRO ratio. The findings support the view that deficit schizophrenia is a distinct subtype of schizophrenia that may be significantly discriminated from nondeficit schizophrenia. Deficit schizophrenia is accompanied by a highly specific defect in IgM isotype-mediated regulatory responses directed to the TRYCAT pathway. Lowered IgM regulatory responses together with mucosa-derived activation of the TRYCAT pathway may contribute to neuroprogression, negative symptoms, and deficit schizophrenia. All in all, a highly specific defect in the compensatory (anti-)inflammatory reflex system (CIRS), namely, natural IgM-mediated regulatory responses, may underpin deficit schizophrenia.
缺陷型精神分裂症伴随着色氨酸分解代谢产物（TRYCAT）途径的黏膜相关激活，表现为对有害（NOX）TRYCAT 的 IgA 反应增加，但对调节或保护（PRO）TRYCAT 无反应，表明其具有更强的神经毒性、兴奋毒性、炎症和氧化潜力。以前没有研究检测过缺陷型与非缺陷型精神分裂症患者的 TRYCAT 途径中 IgM 介导的自身免疫反应。我们测量了 40 名健康对照者、40 名缺陷型和 40 名非缺陷型精神分裂症患者对 NOX TRYCAT（即喹啉酸（QA）、3-羟基犬尿氨酸（3HK）、吡啶酸（PA）和黄尿酸（XA））和 PRO TRYCAT（包括犬尿氨酸（KA）和邻氨基苯甲酸（AA））的 IgM 反应。我们计算了 NOX（QA+PA+3HK+XA）/PRO（AA+KA）比值以及 IgA-IgM TRYCAT 值和 NOX/PRO 比值的差异。与非缺陷型精神分裂症和健康对照者相比，缺陷型精神分裂症患者的所有 TRYCAT 和 NOX/PRO 比值以及 IgA-IgM NOX/PRO 比值的 IgM 反应明显减弱。精神分裂症的阴性症状与针对 KA/3HK 比值和 IgA-IgM NOX/PRO 比值的增加的 IgM 反应呈显著正相关。这些发现支持了这样一种观点，即缺陷型精神分裂症是一种独特的精神分裂症亚型，可能与非缺陷型精神分裂症有明显的区别。缺陷型精神分裂症伴有针对 TRYCAT 途径的 IgM 同种型调节反应的高度特异性缺陷。较低的 IgM 调节反应与 TRYCAT 途径的黏膜衍生激活一起可能导致神经进展、阴性症状和缺陷型精神分裂症。总之，补偿性（抗炎）反射系统（CIRS），即天然 IgM 介导的调节反应的高度特异性缺陷，可能是缺陷型精神分裂症的基础。
