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Deficit schizophrenia and its features are associated with PON1 Q192R genotypes and lowered paraoxonase 1 (PON1) enzymatic activity: effects on bacterial translocation

Published online by Cambridge University Press:  23 June 2020

Andressa K. Matsumoto ,
Michael Maes Open the ORCID record for Michael Maes [Opens in a new window] ,
Thitiporn Supasitthumrong Open the ORCID record for Thitiporn Supasitthumrong [Opens in a new window] ,
Annabel Maes ,
Ana P. Michelin ,
Laura de Oliveira Semeão ,
João V. de Lima Pedrão ,
Estefania G. Moreira ,
Buranee Kanchanatawan  and
Decio S. Barbosa
Andressa K. Matsumoto
Affiliation:
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
Michael Maes*
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria IMPACT Strategic Research Center, Deakin University, Geelong, Australia
Thitiporn Supasitthumrong*
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Ana P. Michelin
Affiliation:
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
Laura de Oliveira Semeão
Affiliation:
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
João V. de Lima Pedrão
Affiliation:
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
Estefania G. Moreira
Affiliation:
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
Buranee Kanchanatawan
Affiliation:
Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Decio S. Barbosa
Affiliation:
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
*
*Thitiporn Supasitthumrong and Michael Maes, MD, PhD Email Thitiporn.s@chula.ac.th, drmichaelmaes@hotmail.com
*Thitiporn Supasitthumrong and Michael Maes, MD, PhD Email Thitiporn.s@chula.ac.th, drmichaelmaes@hotmail.com
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Abstract

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 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.

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 toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

Keywords

Deficit schizophreniaantioxidantsbacteriainflammationoxidative and nitrosative stress

Information

Type
Original Research
Information
CNS Spectrums , Volume 26 , Issue 4 , August 2021 , pp. 406 - 415
Copyright
© The Author(s), 2020. Published by Cambridge University Press

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Footnotes

Buranee Kanchanatawan and Decio S. Barbosa shared senior authorship

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