Genotype-phenotype Analysis of Paraoxonase 1 in Schizophrenic Patients Treated with Atypical Antipsychotics

Pavǎl, Denis; Nemeş, B.; Rusu, Razvan; Dronca, Eleonora

doi:10.9758/cpn.2018.16.1.32

Cited by 10 publications

(15 citation statements)

References 22 publications

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“…In polymedicated SCZ patients, most studies report normal AREase [12,53] and POase [53][54][55][56] activities. Lower AR-Ease activity was reported by Paval et al [57], who also reported lowered POase activity in QQ patients taking olanzapine, but not other atypical antipsychotics. Ünsal et al [58] found lower POase activity in patients who were taking olanzapine (data not adjusted for PON1 Q192R genotype), but not quetiapine.…”

Section: Pon1 and Schizophreniasupporting

confidence: 47%

“…Regarding PON1 polymorphisms, neither Matsumoto et al [62] or Paval et al [57] found an association between the Q192R polymorphism and SCZ. On the other hand, Kuçukali et al [59] reported that the RR genotype was more prevalent in SCZ patients than controls, whilst Paval et al [57] reported that the LL genotype was more prevalent in SCZ.…”

Section: Pon1 and Schizophreniamentioning

confidence: 90%

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Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

et al. 2019

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Background: Nitro-oxidative stress (NOS) has been implicated in the pathophysiology of psychiatric disorders. The activity of the polymorphic antioxidant enzyme paraoxonase 1 (PON1) is altered in diseases where NOS is involved. PON1 activity may be estimated using different substrates some of which are influenced by PON1 polymorphisms. Objectives: 1) to review the association between PON1 activities and psychiatric diseases using a standardized PON1 substrate terminology in order to offer a state-of-the-art review; and 2) to review the efficacy of different strategies (nutrition, drugs, lifestyle) to enhance PON1 activities. Methods: The PubMed database was searched using the terms paraoxonase 1 and psychiatric diseases. Moreover, the database was also searched for clinical trials investigating strategies to enhance PON1 activity. Results: The studies support decreased PON1 activity as determined using phenylacetate (i.e., arylesterase or AREase) as a substrate, in depression, bipolar disorder, generalized anxiety disorder (GAD) and schizophrenia, especially in antipsychotic-free patients. PON1 activity as determined with paraoxon (i.e., POase activity) yields more controversial results, which can be explained by the lack of adjustment for the Q192R polymorphism. The few clinical trials investigating the influence of nutritional, lifestyle and drugs on PON1 activities in the general population suggest that some polyphenols, oleic acid, Mediterranean diet, no smoking, being physically active and statins may be effective strategies that increase PON1 activity. Conclusion: Lowered PON1 activities appear to be a key component in the ongoing NOS processes that accompany affective disorders, GAD and schizophrenia. Treatments increasing attenuated PON1 activity could possibly be new drug targets for treating these disorders.

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Section: Pon1 and Schizophreniasupporting

confidence: 47%

Section: Pon1 and Schizophreniamentioning

confidence: 90%

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

et al. 2019

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“…In patients with chronic schizophrenia, on the other hand, there was no significant decrease in PON1 activity (Boll et al, 2017), although the lack of any changes in PON1 activity could be explained by stimulatory effects of risperidone on PON1 activity . A recent study suggests a possible involvement of low CMPAase in the increased cardiovascular (CVD) risk in patients with SCZ (Pavăl et al, 2018). Gupta et al (2011) found lower CMPAase PON1 activity in CVD patients as compared to controls, independent of age, sex, smoking, alcohol and HDL-C levels.…”

Section: Discussionmentioning

confidence: 99%

In Schizophrenia, PON1 Q192R Genotypes and/or Lowered Paraoxonase 1 (PON1) Enzymatic Activity are Significantly Associated with the Deficit Syndrome, Negative Symptoms, Formal Thought Disorders, Psychomotor Retardation, Excitation and Increased IgA Levels to Gram-Negative Microbiota

Matsumoto¹,

Maes²,

Maes³

et al. 2019

Preprint

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Background: 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. Methods: In this case-control study, Thai women and men, aged 18-65 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 IgA levels responses directed to Gram-negative bacteria were measured. Results: 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. Conclusions: 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 towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

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“…However, there is little evidence that resolves the question of whether genetic variants in MTHFR C677T impair the efficacy of MTHFR in converting 5,10-MTHF to 5-MTHF formation in schizophrenia patients. The PON1 SNP variant was reported to provide a protective role; however, the genotypes, 192 QR and RR, are associated with higher levels of homocysteine [11], and significantly lower AREase activity was found in schizophrenic patients, along with significantly lower PONase activity in olanzapine-treated patients with the QQ genotype [12].…”

Section: Introductionmentioning

confidence: 99%

Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms

Syifa

et al. 2022

Nutrients

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Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC–MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 μL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.

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Genotype-phenotype Analysis of Paraoxonase 1 in Schizophrenic Patients Treated with Atypical Antipsychotics

Cited by 10 publications

References 22 publications

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

In Schizophrenia, PON1 Q192R Genotypes and/or Lowered Paraoxonase 1 (PON1) Enzymatic Activity are Significantly Associated with the Deficit Syndrome, Negative Symptoms, Formal Thought Disorders, Psychomotor Retardation, Excitation and Increased IgA Levels to Gram-Negative Microbiota

Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms

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