PMID- 32754898 OWN - NLM STAT- MEDLINE DCOM- 20210629 LR - 20210629 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 57 IP - 11 DP - 2020 Nov TI - Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: a Nomothetic Network Psychiatry Approach. PG - 4578-4597 LID - 10.1007/s12035-020-02047-5 [doi] AB - 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)-alpha, 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 schizophrenia increases, multiple immune and oxidative (especially protein oxidation indicating chlorinative stress) neurotoxicities and impairments in immune-protective resilience become more prominent and shape a distinct nosological entity, namely deficit schizophrenia. The nomothetic network psychiatry approach allows building causal-pathway-phenotype models using machine learning techniques. FAU - Maes, Michael AU - Maes M AUID- ORCID: 0000-0002-2012-871X AD - Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. dr.michaelmaes@hotmail.com. AD - Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com. AD - IMPACT Strategic Research Center, Deakin University, Geelong, Australia. dr.michaelmaes@hotmail.com. FAU - Sirivichayakul, Sunee AU - Sirivichayakul S AD - Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. FAU - Matsumoto, Andressa Keiko AU - Matsumoto AK AD - Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil. FAU - Michelin, Ana Paula AU - Michelin AP AD - Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil. FAU - de Oliveira Semeao, Laura AU - de Oliveira Semeao L AD - Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil. FAU - de Lima Pedrao, Joao Victor AU - de Lima Pedrao JV AD - Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil. FAU - Moreira, Estefania G AU - Moreira EG AD - Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil. FAU - Barbosa, Decio S AU - Barbosa DS AD - Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, PR, Brazil. FAU - Carvalho, Andre F AU - Carvalho AF AD - IMPACT Strategic Research Center, Deakin University, Geelong, Australia. AD - Department of Psychiatry, University of Toronto and Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada. FAU - Solmi, Marco AU - Solmi M AD - Neurosciences Department, University of Padua, Padua, Italy. FAU - Kanchanatawan, Buranee AU - Kanchanatawan B AD - Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. LA - eng GR - nu/Asahi Glass Foundation/ GR - RA60/042/Ratchada Funds/ GR - RA61/050/Ratchada Funds/ PT - Journal Article DEP - 20200805 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Antioxidants) RN - 0 (Biomarkers) SB - IM MH - Adult MH - Antioxidants/*metabolism MH - Biomarkers/metabolism MH - Case-Control Studies MH - Cognition MH - Female MH - Genome, Human MH - Humans MH - Least-Squares Analysis MH - Linear Models MH - Male MH - Multivariate Analysis MH - *Oxidative Stress MH - Schizophrenia/diagnosis/*pathology MH - *Schizophrenic Psychology OTO - NOTNLM OT - Antioxidants OT - Biomarkers OT - Inflammation OT - Neuro-immune OT - Oxidative stress OT - Tryptophan EDAT- 2020/08/06 06:00 MHDA- 2021/06/30 06:00 CRDT- 2020/08/06 06:00 PHST- 2020/05/15 00:00 [received] PHST- 2020/07/28 00:00 [accepted] PHST- 2020/08/06 06:00 [pubmed] PHST- 2021/06/30 06:00 [medline] PHST- 2020/08/06 06:00 [entrez] AID - 10.1007/s12035-020-02047-5 [pii] AID - 10.1007/s12035-020-02047-5 [doi] PST - ppublish SO - Mol Neurobiol. 2020 Nov;57(11):4578-4597. doi: 10.1007/s12035-020-02047-5. Epub 2020 Aug 5.