BackgroundPrimary 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.MethodsIn 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.ResultsDS 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.ConclusionsThe 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.

中文翻译：

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缺陷型精神分裂症及其特征与 PON1 Q192R 基因型和降低的对氧磷酶 1 (PON1) 酶活性相关：对细菌易位的影响

背景原发性缺陷型精神分裂症 (DS) 的特征是持续存在阴性症状，并且代表与非缺陷型精神分裂症 (NDS) 相比在性质上不同的疾病实体。没有研究调查对氧磷酶 1 (PON1) 和 DS 之间的关系及其现象学。 = 40) 并与对照 (n = 40) 进行比较。确定了针对 4-(氯甲基) 乙酸苯酯 (CMPA) 和乙酸苯酯的 PON1 活性。此外，还对受试者的 PON1 Q192R 多态性进行了基因分型，并测量了针对革兰氏阴性菌的免疫球蛋白 A (IgA) 水平反应。结果与 NDS 和对照组相比，DS 与 QQ 基因型和 Q 等位基因显着相关。PON1 活动与阴性症状、形式思维障碍、精神运动迟缓、兴奋和 DS 显着负相关。Q 等位基因的存在与增加的 IgA 反应有关铜绿假单胞菌、摩根氏菌、和恶臭假单胞菌与 RR 携带者相比。结论 PON1 Q 等位基因和较低的 PON1 活性（尤其是针对 CMPA）与 DS 相关，表明群体淬灭能力降低以及对脂质过氧化和免疫激活的防御能力降低。这表明 DS 中降低的 PON1 活性构成了先天免疫系统的损害，这与降低的天然 IgM 一起可能导致免疫调节降低，从而导致免疫炎症、氧化和亚硝化途径以及革兰氏阴性微生物群产生更大的神经毒性作用。