Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil.
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
CNS Spectr. 2021 Aug;26(4):406-415. doi: 10.1017/S1092852920001388. Epub 2020 Jun 23.
Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology.
In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured.
DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers.
The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.
原发性缺损精神分裂症（DS）的特征是持久的阴性症状，与非缺损精神分裂症（NDS）相比，代表一种具有不同质量的疾病实体。目前尚无研究调查酶对氧磷酶 1（PON1）与 DS 及其表型之间的关系。
在这项病例对照研究中，将年龄在 18 至 65 岁之间的泰国男女分为 DS（n = 40）和 NDS（n = 40）组，并与对照组（n = 40）进行比较。测定 PON1 对 4-（氯甲基）苯乙酸酯（CMPA）和苯乙酸的活性。此外，对研究对象的 PON1 Q192R 多态性进行基因分型，并测量针对革兰氏阴性菌的免疫球蛋白 A（IgA）水平反应。
与 NDS 和对照组相比，DS 与 QQ 基因型和 Q 等位基因显著相关。PON1 活性与阴性症状、形式思维障碍、精神运动迟缓、兴奋和 DS 呈显著负相关。与 RR 携带者相比，Q 等位基因的存在与铜绿假单胞菌、摩根摩根菌和恶臭假单胞菌的 IgA 反应增加相关。
PON1 Q 等位基因和 PON1 活性降低，特别是对 CMPA 的活性降低，与 DS 相关，表明群体感应淬灭能力降低，以及对脂过氧化和免疫激活的防御降低。研究认为，DS 中 PON1 活性降低构成了固有免疫系统的损伤，与天然 IgM 降低一起，可能导致较低的免疫调节，从而更容易受到免疫炎症、氧化和硝化途径以及革兰氏阴性菌群的神经毒性影响。
