PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity
Version 1
: Received: 12 November 2019 / Approved: 12 November 2019 / Online: 12 November 2019 (17:02:22 CET)
How to cite:
Maes, M.; Sirivichayakul, S.; Matsumoto, A. K.; Maes, A.; Michelin, A. P.; de Oliveira Semeão, L.; de Lima Pedrão, J. V.; Moreira, E. G.; Barbosa, D. S.; Geffard, M.; Carvalho, A. F.; Kanchanatawan, B. Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity. Preprints2019, 2019110135. https://doi.org/10.20944/preprints201911.0135.v1
Maes, M.; Sirivichayakul, S.; Matsumoto, A. K.; Maes, A.; Michelin, A. P.; de Oliveira Semeão, L.; de Lima Pedrão, J. V.; Moreira, E. G.; Barbosa, D. S.; Geffard, M.; Carvalho, A. F.; Kanchanatawan, B. Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity. Preprints 2019, 2019110135. https://doi.org/10.20944/preprints201911.0135.v1
Maes, M.; Sirivichayakul, S.; Matsumoto, A. K.; Maes, A.; Michelin, A. P.; de Oliveira Semeão, L.; de Lima Pedrão, J. V.; Moreira, E. G.; Barbosa, D. S.; Geffard, M.; Carvalho, A. F.; Kanchanatawan, B. Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity. Preprints2019, 2019110135. https://doi.org/10.20944/preprints201911.0135.v1
APA Style
Maes, M., Sirivichayakul, S., Matsumoto, A. K., Maes, A., Michelin, A. P., de Oliveira Semeão, L., de Lima Pedrão, J. V., Moreira, E. G., Barbosa, D. S., Geffard, M., Carvalho, A. F., & Kanchanatawan, B. (2019). Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity. Preprints. https://doi.org/10.20944/preprints201911.0135.v1
Chicago/Turabian Style
Maes, M., Andre F. Carvalho and Buranee Kanchanatawan. 2019 "Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity" Preprints. https://doi.org/10.20944/preprints201911.0135.v1
Abstract
Accumulating evidence suggests that TNF-α-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-α and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in schizophrenia patients with (n=40) and without (n=40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial Least Squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-α and PON1 status (QQ genotype and lowered CMPAase activity), lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-α and lowered IL-4, IgM to MDA and education. In addition, both TNF-α and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-α was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.
Medicine and Pharmacology, Psychiatry and Mental Health
Copyright:
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