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In Schizophrenia, Deficits in Natural IgM Isotype Antibodies Including those Directed to Malondialdehyde and Azelaic Acid Strongly Predict Negative Symptoms, Neurocognitive Impairments, and the Deficit Syndrome

  • Michael MaesEmail author
  • Buranee Kanchanatawan
  • Sunee Sirivichayakul
  • André F. Carvalho
Article

Abstract

Schizophrenia is characterized by an interrelated activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), which downregulates the IRS. Deficit schizophrenia is characterized by a deficit in IgM-mediated autoimmune responses to tryptophan catabolites. The presence and correlates of IgM isotype antibodies to oxidative-specific epitopes (OSEs), nitroso (NO), and nitro (NO2) adducts in schizophrenia remain unknown. This study measured IgM antibodies to malondialdehyde (MDA), azelaic acid, phosphatidylinositol, oleic acid, NO-tryptophan, NO-albumin, NO-cysteinyl, and NO2-tyrosine in a sample of 80 schizophrenia patients, divided into those with and those without deficit schizophrenia, and 38 healthy controls. Deficit schizophrenia was characterized by significantly lower IgM antibody levels to all OSEs as compared with non-deficit schizophrenia and controls. Lowered IgM antibodies to MDA coupled with increased IgM levels to NO-cysteinyl and NO2-tyrosine strongly predict deficit schizophrenia versus non-deficit schizophrenia with an area under the ROC curve of 0.913. A large part of the variance (21.2–42.2%) in the negative symptoms of schizophrenia and excitation is explained by IgM antibody titers to MDA (inversely) and NO-cysteinyl and/or NO2-tyrosine (both positively). Lower IgM antibodies to MDA are significantly associated with impairments in episodic memory including direct and delayed recall. These findings further indicate that deficit schizophrenia is a distinct phenotype of schizophrenia, which is characterized by lower natural IgM antibody levels to OSEs and relative increments in nitrosylation and nitration of proteins. It is concluded that deficits in natural IgM attenuate CIRS functions and that this impairment may drive negative symptoms and impairments in episodic memory and thus deficit schizophrenia.

Keywords

Immune Inflammation Natural IgM autoimmune Oxidative stress Kynurenine Schizophrenia Psychosis 

Notes

Acknowledgements

The study was supported by the Asahi Glass Foundation, Chulalongkorn University Centenary Academic Development Project and Ratchadapiseksompotch Funds, Faculty of Medicine, Chulalongkorn University, grant numbers RA60/042 and RA61/050.

Author’s Contributions

All the contributing authors have participated in the manuscript. MM and BK designed the study. BK recruited patients and completed diagnostic interviews and rating scale measurements. MM carried out the statistical analyses. All authors (BK, SS, MM, and AC) contributed to the interpretation of the data and writing of the manuscript. All authors approved the final version of the manuscript.

Compliance with Ethical Standards

The study was conducted according to International and Thai ethics and privacy laws.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 1.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  2. 2.Department of PsychiatryMedical University of PlovdivPlovdivBulgaria
  3. 3.IMPACT Strategic Research Center, Barwon HealthDeakin UniversityGeelongAustralia
  4. 4.Faculty of MedicineChulalongkorn UniversityBangkokThailand
  5. 5.Department of PsychiatryUniversity of TorontoTorontoCanada
  6. 6.Centre for Addiction and Mental Health (CAMH)TorontoCanada

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