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1.
Proc Natl Acad Sci U S A ; 117(12): 6651-6662, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32152116

RESUMO

A role for microglia in neuropsychiatric diseases, including major depressive disorder (MDD), has been postulated. Regulation of microglial phenotype by immune receptors has become a central topic in many neurological conditions. We explored preclinical and clinical evidence for the role of the CD300f immune receptor in the fine regulation of microglial phenotype and its contribution to MDD. We found that a prevalent nonsynonymous single-nucleotide polymorphism (C/T, rs2034310) of the human CD300f receptor cytoplasmic tail inhibits the protein kinase C phosphorylation of a threonine and is associated with protection against MDD, mainly in women. Interestingly, CD300f-/- mice displayed several characteristic MDD traits such as augmented microglial numbers, increased interleukin 6 and interleukin 1 receptor antagonist messenger RNA, alterations in synaptic strength, and noradrenaline-dependent and persistent depressive-like and anhedonic behaviors in females. This behavioral phenotype could be potentiated inducing the lipopolysaccharide depression model. RNA sequencing and biochemical studies revealed an association with impaired microglial metabolic fitness. In conclusion, we report a clear association that links the function of the CD300f immune receptor with MDD in humans, depressive-like and anhedonic behaviors in female mice, and altered microglial metabolic reprogramming.


Assuntos
Anedonia , Transtorno Depressivo Maior/patologia , Inflamação/etiologia , Microglia/patologia , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genética , Receptores Imunológicos/fisiologia , Animais , Comportamento Animal , Estudos de Coortes , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/psicologia , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Sinapses
2.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 40(1): 1-5, Jan.-Mar. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-899410

RESUMO

Objective: To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. Methods: This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores ≥ 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). Results: Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. Conclusion: These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Transtornos do Humor/epidemiologia , Alcoolismo/epidemiologia , Ansiedade/complicações , Fatores Socioeconômicos , Brasil/epidemiologia , Drogas Ilícitas , Comorbidade , Prevalência , Estudos Transversais , Inquéritos e Questionários , Fatores de Risco , Alcoolismo/psicologia
3.
Braz J Psychiatry ; 40(1): 1-5, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28658442

RESUMO

OBJECTIVE: To evaluate the prevalence of alcohol abuse and/or dependence in a population-based sample of young adults and assess the prevalence of comorbid mood disorders, anxiety, and suicide risk in this population. METHODS: This cross-sectional, population-based study enrolled 1,953 young adults aged 18-35 years. The CAGE questionnaire was used to screen for alcohol abuse and/or dependence, with CAGE scores ≥ 2 considered positive. Psychiatric disorders were investigated through the structured Mini International Neuropsychiatric Interview (MINI). RESULTS: Alcohol abuse and/or dependence was identified in 187 (9.60%) individuals (5.10% among women and 15.20% among men). Alcohol abuse and/or dependence were more prevalent among men than women, as well as among those who used tobacco, illicit drugs or presented with anxiety disorder, mood disorder, and suicide risk. CONCLUSION: These findings suggest that alcohol abuse and/or dependence are consistently associated with a higher prevalence of psychiatric comorbidities, could be considered important predictors of other psychiatric disorders, and deserve greater public heath attention, pointing to the need for alcohol abuse prevention programs.


Assuntos
Alcoolismo/epidemiologia , Transtornos de Ansiedade/epidemiologia , Ansiedade/epidemiologia , Transtornos do Humor/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Adulto , Alcoolismo/psicologia , Ansiedade/complicações , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Drogas Ilícitas , Masculino , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
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