Food and nutritional insecurity is associated with depressive symptoms mediated by NR3C1 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 - NR3C1-1F - 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 NR3C1-1F 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 NR3C1 DNA methylation, FNiS, and depressive symptoms. Multivariate Poisson regression with robust variance adjusted for sex and FNiS and NR3C1-1F region methylation predicted risk factors for depressive symptoms. Mediation analysis revealed that NR3C1-1F 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 NR3C1 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 NR3C1-1F DNA methylation can act as a mediator of both FNiS and depressive symptoms.

Keywords: DNA methylation; NR3C1; Stress; depression; epigenetic; food and nutritional insecurity.