RESUMEN
There is a two-fold higher incidence of depression in females compared to men with recent studies suggesting a role for microglia in conferring this sex-dependent depression risk. In this study we investigated the nature of this relation. Using GWAS enrichment, gene-set enrichment analysis and Mendelian randomization, we found minimal evidence for a direct relation between genes functionally related to microglia and sex-dependent genetic risk for depression. We then used expression quantitative trait loci and single nucleus RNA-sequencing resources to generate polygenic scores (PGS) representative of individual variation in microglial function in the adult (UK Biobank; N = 54753-72682) and fetal (ALSPAC; N = 1452) periods. The adult microglial PGS moderated the association between BMI (UK Biobank; beta = 0.001, 95 %CI 0.0009 to 0.003, P = 7.74E-6) and financial insecurity (UK Biobank; beta = 0.001, 95 %CI 0.005 to 0.015, P = 2E-4) with depressive symptoms in females. The fetal microglia PGS moderated the association between maternal prenatal depressive symptoms and offspring depressive symptoms at 24 years in females (ALSPAC; beta = 0.04, 95 %CI 0.004 to 0.07, P = 0.03). We found no evidence for an interaction between the microglial PGS and depression risk factors in males. Our results illustrate a role for microglial function in the conferral of sex-dependent depression risk following exposure to a depression risk factor.
Asunto(s)
Depresión , Microglía , Humanos , Microglía/metabolismo , Femenino , Masculino , Depresión/metabolismo , Adulto , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Embarazo , Factores Sexuales , Predisposición Genética a la Enfermedad , Factores de Riesgo , Sitios de Carácter Cuantitativo , Interacción Gen-Ambiente , Adulto Joven , Efectos Tardíos de la Exposición Prenatal/metabolismo , Caracteres Sexuales , Análisis de la Aleatorización MendelianaRESUMEN
Infancy and early childhood are important periods for the development of food choices and eating preferences that are tracked into adult life influencing weight gain, body composition, metabolism, and ultimately affecting the balance between health and disease. In this narrative review, we aimed at discussing studies focused on the effects of fetal programming and early food experiences, highlighting recent advances in the discovery of factors that contribute to the development of food preferences and eating behavior. Food preference can be influenced by early direct contact with flavors, textures, and aromas, as well as by environmental adversities during early development. Evidence suggests that exposure to intrauterine growth restriction is associated with an increased preferences for highly palatable foods such as those rich in carbohydrates and fats over the life-course. Early flavor experiences, whether from amniotic fluid or human milk, may also shape the development of food preferences. Finally, children are more likely to accept textures that they are able to manipulate, and early exposure to a range of textures facilitates the acceptance of foods of various textures later on. Improving diet habits during gestation (fetal) and postnatal periods is of critical importance for the establishment of positive eating habits and healthy growth in infants and should be an important focus of primary prevention efforts.
RESUMEN
Nutrition in pregnancy, during lactation, childhood, and later stages has a fundamental influence on overall development. There is a growing research interest on the role of key dietary nutrients in fetal health. Omega-3 polyunsaturated fatty acids (n-3 LCPUFAs) play an important role in brain development and function. Evidence from animal models of dietary n-3 LCPUFAs deficiency suggests that these fatty acids promote early brain development and regulate behavioral and neurochemical aspects related to mood disorders (stress responses, depression, and aggression and growth, memory, and cognitive functions). Preclinical and clinical studies suggest the role of n-3 LCPUFAs on neurodevelopment and growth. n-3 LCPUFAs may be an effective adjunctive factor for neural development, growth, and cognitive development, but further large-scale, well-controlled trials and preclinical studies are needed to examine its clinical mechanisms and possible benefits. The present paper discusses the use of n-3 LCPUFAs during different developmental stages and the investigation of different sources of consumption. The paper summarizes the role of n-3 LCPUFAs levels during critical periods and their effects on the children's neurodevelopment, nutrition, and growth.