ABSTRACT
Latina mothers, who have the highest fertility rate among all ethnic groups in the US, are often exposed to discrimination. The epigenetic changes related to this discrimination are largely unknown. This study is the first to explore the relationship between discrimination and DNA methylation of stress regulatory genes in Latinas. Our sample was Latina women (n = 147) with a mean age of 27.6 years who were assessed at 24-32 weeks' gestation (T1) and 4-6 weeks postpartum (T2) and reside in the U.S. Blood was collected at T1, and the Everyday Discrimination Scale (EDS) was administered at T1 and T2. DNA Methylation at candidate gene regions was determined by bisulphite pyrosequencing. Associations between EDS and DNA methylation were assessed via zero-inflated Poisson models, adjusting for covariates and multiple-test comparisons. Discrimination was negatively associated with methylation at CpG sites within the glucocorticoid receptor (NR3C1) and brain-derived neurotrophic factor (BDNF) genes that were consistent over time. In addition, discrimination was negatively associated with methylation of a CpG in the glucocorticoid binding protein (FKBP5) at T1 but not at T2. This study underscores associations between discrimination and epigenetic markers of DNA methylation in Latinas that warrant further investigation to better understand the biological pathways and psychopathological effects of discrimination on Latina mothers and their families.
Subject(s)
Hispanic or Latino/genetics , Social Discrimination/psychology , Stress, Psychological/genetics , Adult , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , CpG Islands/genetics , DNA Methylation/genetics , Epigenesis, Genetic/genetics , Female , Hispanic or Latino/psychology , Humans , Hydrocortisone , Mothers , Neuronal Plasticity , Pregnancy , Promoter Regions, Genetic/genetics , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Stress, Psychological/metabolism , Tacrolimus Binding Proteins/genetics , Tacrolimus Binding Proteins/metabolismABSTRACT
Studies show that adverse conditions during early life can increase risks of developing mood disorders later in life. It is currently hypothesized that levels of environmental adversity in this early developmental period are able to shape the experience-dependent maturation of stress-regulating pathways leading to long-lasting alterations in stress responsivity during adulthood; a phenomenon often referred to as "early-life programming." Research is addressing the molecular mechanisms underlying this programming by which gene-environment interactions can predispose individuals toward psychopathology. Here we review key findings from animal and clinical studies examining the effects of prenatal and postnatal environment in shaping development of the neuroendocrine regulation of stress and the role of epigenetic mechanisms in translating early-life conditions into long-lasting gene expression changes underpinning stress-related behaviors. We also review latest ideas regarding interactions between environments at different developmental stages and evidence for transgenerational effects. Understanding how prenatal and postnatal experiences can give rise to lasting epigenetic marks conferring increased vulnerability to mental disorders is a major focus of molecular psychiatry and should pave new guidelines for therapeutic interventions.
