Food and nutritional insecurity is associated with depressive symptoms mediated by <i>NR3C1</i> gene promoter 1F methylation

Abstract

The aim of this study was to investigate socioeconomic stressors predictive of depressive symptoms and possible epigenetic changes in the glucocorticoid receptor - <i>NR3C1</i>-1F - an encoding gene involved in depressive symptoms. A total of 321 adult volunteers from southeastern Brazil were recruited to evaluate depressive symptoms, socio-demographic and economic factors, including food and nutritional security (FNS) or insecurity (FNiS) status, and <i>NR3C1</i>-1F region methylation by pyrosequencing. Depressive symptom determinants were investigated using a Poisson regression model with robust variance. Mann-Whitney tests and structural mediation equation models were used to evaluate the relationship between <i>NR3C1</i> DNA methylation, FNiS, and depressive symptoms. Multivariate Poisson regression with robust variance adjusted for sex and FNiS and <i>NR3C1</i>-1F region methylation predicted risk factors for depressive symptoms. Mediation analysis revealed that <i>NR3C1</i>-1F region methylation mediated the relationship between FNiS exposure and depressive symptoms as an outcome, and depressive volunteers and FNiS individuals exhibited a significant increase in <i>NR3C1</i> methylation when compared to healthy individuals and FNS volunteers, respectively. Therefore, we suggest that stress caused by FNiS may lead to depressive symptoms and that <i>NR3C1</i>-1F DNA methylation can act as a mediator of both FNiS and depressive symptoms.