RESUMEN
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.
Asunto(s)
Anhedonia , Trastorno Depresivo Mayor/patología , Inflamación/etiología , Microglía/patología , Polimorfismo de Nucleótido Simple , Receptores Inmunológicos/genética , Receptores Inmunológicos/fisiología , Animales , Conducta Animal , Estudios de Cohortes , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/psicología , Femenino , Perfilación de la Expresión Génica , Humanos , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/metabolismo , SinapsisRESUMEN
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.
Asunto(s)
Alcoholismo/epidemiología , Trastornos de Ansiedad/epidemiología , Ansiedad/epidemiología , Trastornos del Humor/epidemiología , Intento de Suicidio/estadística & datos numéricos , Adolescente , Adulto , Alcoholismo/psicología , Ansiedad/complicaciones , Brasil/epidemiología , Comorbilidad , Estudios Transversales , Femenino , Humanos , Drogas Ilícitas , Masculino , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
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.