Psychotropic drug use and suggestive depression symptoms associated with NR3C1 DNA methylation / Uso de drogas psicotrópicas e sintomas sugestivos de depressão associados à metilação do DNA do NR3C1

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.

Introdução: os distúrbios psiquiátricos tornaram-se um problema global que leva milhões de pessoas ao uso de medicamentos psicotrópicos. Os efeitos dessas substâncias são amplamente conhecidos quanto à tolerância e dependência química, porém, do ponto de vista epigenético, ainda são pouco conhecidos.Objetivos: avaliar a associação entre o uso de drogas psicotrópicas, metilação do gene NR3C1 e sua relação com sintomas sugestivos de depressão em indivíduos entre 20 a 59 anos usuários da rede pública de saúde.Método: 385 voluntários de 20-59 anos, usuários do Sistema Único de Saúde brasileiro foram recrutados para avaliação das condições socioeconômicas, de saúde e de estilo de vida em estudo transversal. O BDI-II avaliou sintomas sugestivos de depressão e o pirosequenciamento avaliou a metilação do DNA de NR3C1. Modelo de regressão de Poisson bivariado e multivariado com variância robusta (p < 0,05) avaliou a associação entre o uso de drogas psicotrópicas e metilação do gene NR3C1.Resultados: sintomas depressivos específicos como irritabilidade, insônia e fadiga foram associados ao uso de medicamentos psicotrópicos. Sintomas de fracasso passado, indecisão e perda de apetite foram associados a padrões de hipermetilação nos CpGs 40 a 47 do gene NR3C1. Além disso, o uso de psicofármacos está associado à redução de 50% na metilação do gene NR3C1, por meio de modelo ajustado com variáveis de confusão socioeconômicas, de saúde e estilo de vida.Conclusão: o uso de drogas psicotrópicas e sintomas específicos depressivos foram associados a alterações na metilação do DNA de NR3C1.

Epigenetic alteration of BDNF gene, social and health status as predictors of food and nutrition insecurity among familiar coffee farmers / Alteração epigenética no gene BDNF, status social e de saúde como preditores da insegurança alimentar e nutricional em cafeicultores familiares

ntroduction: state of Food and Nutritional Security (FNS) is one that should guarantee the right of permanent access to quality food and in sufficient quantity without prejudicing access to other basic rights. In Brazil, rural family farming establishments represent 84.4% of total agricultural establishments and contribute to more than 70% of all food consumed by Brazilians. In this context, the production of the coffee commodity stands out. However, despite being food producers, they do not earn a good income. Slow economic activity can lead to loss of wages and income, illness, as well as food insecurity (FNiS). In addition, the molecular effects of FNiS are poorly studied, especially epigenetic.Objective: the objective of the present study is to analyze the association between Brain-Derived Neurotrophic Factor (BDNF) DNA methylation and socio demographic, lifestyle, and epigenetic factors, among coffee farmers in the Caparaó zone, in Espirito Santo, Southeast Brazil.Methods: the study was carried out in 22 randomly selected coffee producing communities in Zona Caparaó, an area that produces coffee of recognized quality. A total of 570 coffee farming households, 18 to 60 years of age, were included in the study by answering a questionnaire about socioeconomic characteristics, land use and ownership, behavior, health, and working conditions. FNiS evaluation was carried out using the Brazilian Food Insecurity Scale. BDNF exon I methylation was examined by methylation-specific PCR. Body mass index and biochemical analyses were performed. Logistic regression models were used to verify factors associated with FNiS (p<0.05). Data were analyzed using the Stata® statistical software package version 14.Results: the FNiS prevalence found was 23.68%. In multivariable logistic regression, the occurrence of FNiS was associated with hypermethylation of exon I of the BDNF promoter exon I [ORa = 5.03 (95% (1.98, 12.82)] when compared to the unmethylated gene. Moreover, FNiS was associated with excessive workload [ORa = 3.36 (1.23, 9.22)], possession of less land (hectares) [ORa = 0.77 (0.67, 0.90)] and greater number symptoms and / or illnesses in real life [ORa = 1.12 (1.04.1.20)].Conclusion: there is a high prevalence of Food Insecurity in the studied region. This phenomenon was associated with epigenetic factors (BDNF methylation), excessive workload, small land ownership and a greater number of diseases / symptoms. Food insecurity is a psychosocial stressor that can lead to epigenetic changes in the BDNF gene, responsible for regulating cognitive functions, neuronal survival and involved in the genesis of psychiatric diseases.

Introdução: o Estado de Segurança Alimentar e Nutricional (SAN) é aquele que deve garantir o direito de acesso permanente à alimentação de qualidade e em quantidade suficiente sem prejudicar o acesso a outros direitos básicos. No Brasil, os estabelecimentos de agricultura familiar rural representam 84,4% do total de estabelecimentos agropecuários e contribuem com mais de 70% de todos os alimentos consumidos pelos brasileiros. Nesse contexto, destaca-se a produção da commodity café. No entanto, apesar de serem produtores de alimentos, não auferem bons rendimentos. A lenta atividade econômica pode levar à perda de salários e renda, doenças e insegurança alimentar (INSAN). Além disso, os efeitos moleculares da INSAN são pouco estudados, sobretudo epigenéticos.Objetivos: o objetivo do presente estudo é analisar a associação entre a metilação do promotor do BDNF e a INSAN e a associação da INSAN com fatores sociodemográficos, de estilo de vida e epigenéticos, em cafeicultores da zona do Caparaó, no Espírito Santo, Sudeste do Brasil.Método: o estudo foi realizado em 22 comunidades cafeeiras selecionadas aleatoriamente na Zona do Caparaó, área que produz café de reconhecida qualidade. Um total de 570 famílias de cafeicultores, entre 18 a 60 anos, foram incluídos no estudo e responderam a um questionário sobre características socioeconômicas, uso e posse da terra, hábitos de vida, saúde e condições de trabalho. A avaliação da INSAN foi realizada por meio da Escala Brasileira de Insegurança Alimentar. A metilação do éxon I do BDNF foi examinada por PCR específica para metilação. Índice de massa corporal e análises bioquímicas foram realizadas. Modelos de regressão logística foram utilizados para verificar os fatores associados à INSAN (p<0,05). Os dados foram analisados usando o software estatístico Stata® versão 14.Resultados: a prevalência de INSAN encontrada foi de 23,68%. Na regressão logística multivariada, a ocorrência de INSAN foi associada a hipermetilação do éxon I do promotor do gene BDNF [ORa = 5,03 (95% (1,98, 12,82)] quando comparado ao gene não metilado. Além disso, a INSAN foi associada a carga de trabalho excessiva [ORa = 3,36 (1,23, 9,22)], posse de menos hectares de terra [ORa = 0,77 (0,67, 0,90)] e maior número de sintomas e/ou doenças da vida real [ORa = 1,12 (1.04.1.20)].Conclusão: o estudo mostrou uma alta prevalência de Insegurança Alimentar na região analisada. Esse fenômeno foi associado a fatores epigenéticos (metilação do gene BDNF), carga horária excessiva, pequena propriedade de terra e maior número de doenças/sintomas. A INSAN pode ser um estressor capaz de promover alterações epigenéticas no gene BDNF, importante gene regulador da cognição, crescimento e sobrevivência neuronal e envolvido com doenças psiquiátricas.

Síndrome do eutireoideo doente e alterações nos hormônios tireoidianos em cães com hemoparasitoses / Euthyroid sick syndrome and changes in thyroid hormones in dogs with hemoparasitosis

Background: Hemoparasitoses are extremely important in the clinical routine because they affect a large number of dogs. In spite ofthe abundance of studies on this topic, hormonal alterations caused by infection with these agents are still poorly known. Therefore,the goal of this work was to assess the serum levels of thyroid hormones of dogs infected with Ehrlichia canis (E. canis) alone, anddogs infected with E. canis and Babesia canis vogeli (B. vogeli) and/or Anaplasma platys (A. platys) before and after treatment withdoxycycline chlorohydrate. This study also aimed at checking for presence of euthyroid sick syndrome (ESS) in these animals.Materials, Methods & Results: The concentrations of the thyroid hormones total triiodothyronine (TT3), total tetraiodothyronine (TT4),free tetraiodothyronine (FT4), and canine thyroid-stimulating hormone (cTSH) were assessed by chemiluminescence in 12 dogs. Nestedpolymerase chain reaction (nPCR) was used to confirm diagnoses. The dogs were divided into 2 groups: G1, which comprised animalsinfected by E. canis alone, and G2, which included animals simultaneously infected by E. canis and B. vogeli and/or A. platys. Theserum concentrations of the thyroid hormones were measured at two time points: before (D1) and after (D2) the 28-day treatment withgeneric doxycycline chlorohydrate (DC) at a dose of 10 mg/kg SID. On D2, another nPCR was carried out to check the efficacy of thetreatment. On D2, in both groups, all dogs became negative for E. canis; however, 8 animals remained infected or were reinfected byother hemoparasites. On D1, 4 dogs in G1 exhibited low TT3 in conjunction with low TT4; one of the dogs had increased TT3 alone,and another dog had an increased TT3 accompanied by decreased TT4. In G2, on D1, one dog exhibited high TT3 accompanied by adecreased concentration of TT4; 2 dogs had decreased TT4; 2 dogs had increased TT3; and one dog had both TT3 and TT4 decreased...(AU)

Síndrome do eutireoideo doente e alterações nos hormônios tireoidianos em cães com hemoparasitoses / Euthyroid sick syndrome and changes in thyroid hormones in dogs with hemoparasitosis

Background: Hemoparasitoses are extremely important in the clinical routine because they affect a large number of dogs. In spite ofthe abundance of studies on this topic, hormonal alterations caused by infection with these agents are still poorly known. Therefore,the goal of this work was to assess the serum levels of thyroid hormones of dogs infected with Ehrlichia canis (E. canis) alone, anddogs infected with E. canis and Babesia canis vogeli (B. vogeli) and/or Anaplasma platys (A. platys) before and after treatment withdoxycycline chlorohydrate. This study also aimed at checking for presence of euthyroid sick syndrome (ESS) in these animals.Materials, Methods & Results: The concentrations of the thyroid hormones total triiodothyronine (TT3), total tetraiodothyronine (TT4),free tetraiodothyronine (FT4), and canine thyroid-stimulating hormone (cTSH) were assessed by chemiluminescence in 12 dogs. Nestedpolymerase chain reaction (nPCR) was used to confirm diagnoses. The dogs were divided into 2 groups: G1, which comprised animalsinfected by E. canis alone, and G2, which included animals simultaneously infected by E. canis and B. vogeli and/or A. platys. Theserum concentrations of the thyroid hormones were measured at two time points: before (D1) and after (D2) the 28-day treatment withgeneric doxycycline chlorohydrate (DC) at a dose of 10 mg/kg SID. On D2, another nPCR was carried out to check the efficacy of thetreatment. On D2, in both groups, all dogs became negative for E. canis; however, 8 animals remained infected or were reinfected byother hemoparasites. On D1, 4 dogs in G1 exhibited low TT3 in conjunction with low TT4; one of the dogs had increased TT3 alone,and another dog had an increased TT3 accompanied by decreased TT4. In G2, on D1, one dog exhibited high TT3 accompanied by adecreased concentration of TT4; 2 dogs had decreased TT4; 2 dogs had increased TT3; and one dog had both TT3 and TT4 decreased...