Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: a Nomothetic Netwo
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ORIGINAL ARTICLE
Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: a Nomothetic Network Psychiatry Approach Michael Maes 1,2,3 & Sunee Sirivichayakul 4 & Andressa Keiko Matsumoto 5 & Ana Paula Michelin 5 & Laura de Oliveira Semeão 5 & João Victor de Lima Pedrão 5 & Estefania G. Moreira 5 & Decio S. Barbosa 5 & Andre F. Carvalho 3,6 & Marco Solmi 7 & Buranee Kanchanatawan 1 Received: 15 May 2020 / Accepted: 28 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: to compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (–SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, and total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n = 40) and non-deficit (n = 40) schizophrenia and healthy controls (n = 40). Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered –SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (odds ratio = 3.15, p < 0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, and IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas –SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. When overall severity of
* Michael Maes [email protected]; https://scholar.google.co.th/ citations?user=1wzMZ7UAAAAJ&hl=th&oi=ao
Marco Solmi [email protected] Buranee Kanchanatawan [email protected]
Sunee Sirivichayakul [email protected] 1
Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Ana Paula Michelin [email protected]
2
Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria
Laura de Oliveira Semeão [email protected]
3
IMPACT Strategic Research Center, Deakin University, Geelong, Australia
João Victor de Lima Pedrão [email protected]
4
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Estefania G. Moreira [email protected]
5
Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil
Decio S. Barbosa [email protected]
6
Department of Ps
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