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Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life

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Abstract

Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways. This present study examined the associations among chronic apical periodontitis (CAP), root canal endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms, and quality of life. Measurements included advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), −sulfhydryl (SH) groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase (PON)1 activity in participants with CAP, with and without depression, as well as healthy controls (no depression, no CAP). Root canal LPS levels were positively associated with CAP, clinical depression, severity of depression (as measured with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP participants, there was a strong correlation (r = 0.734, p < 0.001) between root canal LPS and the HDRS score. There were significant and positive associations between CAP or root canal endotoxin with the vegetative and physio-somatic symptoms of the HDRS as well as a significant inverse association between root canal endotoxin and quality of life with strong effects on psychological, environmental, and social domains. It is concluded that increased root canal LPS accompanying CAP may cause depression and a lowered quality of life, which may be partly explained by activated O&NS pathways, especially NOx thereby enhancing hypernitrosylation and thus neuroprogressive processes. Dental health and “leaky teeth” may be intimately linked to the etiology and course of depression, while significantly impacting quality of life.

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Acknowledgements

MM is supported by a CNPq PVE fellowship at the Health Sciences Graduation Program, Universidade Estadual de Londrina. THLB and NRM are supported by CAPES fellowships at the Health Sciences Graduation Program, Universidade Estadual de Londrina. CCG is supported by Institute of Health, School of Dentistry, UFF – Federal Fluminense University, Nova Friburgo, RJ, Brazil. FCM is supported by a FAPESP (Sao Paulo Research Foundation) grant (FAPESP: 2015/03696-1), Sao Paulo, Brazil.

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Authors and Affiliations

  1. Department of Specific Formation, Institute of Health, School of Dentistry, UFF - Federal Fluminense University, Nova Friburgo, RJ, Brazil

    Cinthya Gomes & Leonardo Santos Antunes

  2. Department of Restorative Dentistry, Endodontic Division, Institute of Science and Technology, UNESP - Univ Estadual Paulista, São José dos Campos, SP, Brazil

    Frederico Canato Martinho

  3. Graduation Program in Health Sciences, State University of Londrina (UEL), Paraná, Brazil

    Décio Sabbatini Barbosa, Thiago Hissnauer Leal Baltus, Nayara Rampazzo Morelli, Sandra Odebrecht Vargas Nunes & Michael Maes

  4. Department of Basic Science, Institute of Health, UFF - Universidade Federal Fluminense, Nova Friburgo, RJ, Brazil

    Helvécio Cardoso Corrêa Póvoa

  5. Department of Psychiatry, Health Sciences Center, State University of Londrina, Londrina, Brazil

    Heber Odebrecht Vargas

  6. CRC, London and Scotland, Edinburgh, UK

    George Anderson

  7. Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Michael Maes

  8. Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria

    Michael Maes

  9. Revitalis, Waalre, the Netherlands

    Michael Maes

  10. IMPACT Strategic Research Center, Barwon Health, Deakin University, Geelong, VIC, Australia

    Michael Maes

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  1. Cinthya Gomes
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Contributions

CG, MM, HOV, and SOVN made the design of the study. Participants were recruited and screened by CG. Biomarker assays were performed by FCM, DSB, LSA, HCCP, THLB, and NRM. MM performed the statistical analyses. All authors contributed equally to the writing of the paper. All authors agreed upon the final version of the paper.

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Correspondence to Michael Maes.

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The authors have no conflict of interest with any commercial or other association in connection with the submitted article.

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Gomes, C., Martinho, F.C., Barbosa, D.S. et al. Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life. Mol Neurobiol 55, 2814–2827 (2018). https://doi.org/10.1007/s12035-017-0545-z

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  • DOI: https://doi.org/10.1007/s12035-017-0545-z

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