Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation

Authors

  • Júlia de Assis Pinheiro a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Aline Ribeiro Borçoi a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Flávia Vitorino Freitas a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil; f Departamento de Farmácia e Nutrição, Universidade Federal do Espírito Santo, Alegre, ES, Brasil;
  • Suzanny Oliveira Mendes a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Anderson Barros Archanjo a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Mayara Mota de Oliveira a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Joaquim Gasparini dos Santos a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Juliana Krüger Arpini a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Rafael Assis de Souza dDepartamento de Agronomia, Universidade Federal do Espírito Santo, Alegre, ES, Brasil;
  • Ivana Alece Arantes Moreno a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Marcele Lorentz Mattos de Souza a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Dirceu Pereira dos Santos e Instituto Federal Fluminense, Campos dos Goytacazes, RJ, Brasil;
  • Wagner Miranda Barbosa f Departamento de Farmácia e Nutrição, Universidade Federal do Espírito Santo, Alegre, ES, Brasil;
  • José Claudio Casali-da-Rocha g A.C. Camargo Câncer Center, São Paulo, SP, Brasil;
  • Bruna Pereira Sorroche c Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Barretos – São Paulo, Brasil;
  • Leonardo Oliveira Trivilin h Departamento de Medicina Veterinária, Universidade Federal do Espírito Santo, Alegre, ES, Brasil;
  • Elizeu Batista Borloti i Programa de Graduação em Psicologia, Universidade Federal do Espírito Santo, Vitoria, ES, Brasil.
  • Letícia Batista Azevedo Rangel aBiotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil;
  • Lidia Maria Rebolho Batista Arantes c Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Barretos – São Paulo, Brasil;
  • Adriana Madeira Alvares-da-Silva a Biotecnologia/Renorbio Programa de Pós-Graduação, Universidade Federal do Espírito Santo, ES, Brasil; b Departamento de Biologia, Universidade Federal do Espírito Santo, Alegre, ES, Brasil;

DOI:

https://doi.org/10.36311/jhgd.v33.14300

Keywords:

Methylation, NR3C1, psychotropic drugs use, depressive symptoms

Abstract

Introduction: Psychiatric disorders have become a global problem that leads millions of people to use psychotropic medications, especially benzodiazepines. The effects of these substances are widely known regarding tolerance and chemical dependence, however, from epigenetics perspective, there are still little known.

Objective: To evaluate the association between psychotropic drug use, NR3C1 gene methylation and its relation with symptoms suggestive of depression in adult individuals assisted in the public health system.

Methods: 385 adult volunteers (20-59 years) users of the Brazilian Unified Health System were recruited to evaluate socioeconomic, health, lifestyle conditions in a cross sectional study. BDI-II evaluated symptoms suggestive of depression and pyrosequencing evaluated NR3C1 DNA methylation. Bivariate and multivariate Poisson regression model with robust variance (p < 0.05) evaluated the association between psychotropic drug use and NR3C1 gene methylation.

Results: Specific depressive symptoms such as irritability, insomnia and fatigability were associated with psychotropic drug use. Symptoms of past failure, indecision and loss of appetite were associated with hypermethylation patterns in CpGs 40 to 47 of NR3C1 gene. Moreover, psychotropic drug use is associated with 50% reduction in NR3C1 gene methylation, through model adjusted with socioeconomic, health and lifestyle confounding variables.

Conclusions: Psychotropic drug use and depressive symptoms was associated with changes in NR3C1 DNA methylation. In this context, epigenetic modification resulting from psychotropic drug use and depressive symptoms could be considered, mainly in population studies with epigenetic evaluation, where these factors may be influencing the findings of future studies.

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2023-03-23

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Vol. 33 No. 1 (2023)

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ORIGINAL ARTICLES

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Copyright (c) 2023 Pinheiro JA, Borçoi AR, Freitas FV, Mendes SO, Archanjo AB, Oliveira MM, Santosa JG, Arpini JK, Souza RA, Moreno IAA, Souza MLM, Santos DP, Barbosa WM, Casali-da-Rocha JC, Sorroche BP, Trivilin LO, Borloti EB, Rangel LBA, Arantes LMRB, Alvares-da-Silva AM

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