Presentation Title
Increased risk of mental illness due to epigenetic alteration of the NR3C1 gene after early life adversity.
Document Type
Poster Session
Department
Biological Sciences
Faculty Mentor
Dr. Daniel Moore
Keywords
early life adversity, epigenetics, DNA methylation, mental health, glucocorticoids, maternal care, stress
Abstract
Early life adversity (ELA), such as malnutrition, abuse, and economic disparity, is an issue commonly seen in adolescents, a group already facing increased risk for stress-related disorders. This review of current literature reveals that gestational stress exposure, as well as variations in maternal care during postnatal development, cause latent effects on the epigenome, specifically impacting the glucocorticoid receptors (GRs) encoded by the NR3C1 gene. GRs bind to glucocorticoids to regulate the body’s neuroendocrine stress response. However, in those with a history of ELA, the number of GRs is reduced, generating dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis. Rodent studies are utilized as a translational model of reference since their first weeks postnatal mimic the prenatal window of humans. That said, the details of the DNA methylation pattern at the NR3C1 gene varies, depending on species of rodent, ELA exposure, sex, and age, but there are broad similarities. Overall, due to early life adversity, data shows that epigenomic alterations in the NR3C1 gene produce HPA axis dysregulation which contributes to chronic stress and psychiatric disorders later in life.
Included in
Biology Commons, Genetics and Genomics Commons, Mental and Social Health Commons, Psychiatry and Psychology Commons
Increased risk of mental illness due to epigenetic alteration of the NR3C1 gene after early life adversity.
Early life adversity (ELA), such as malnutrition, abuse, and economic disparity, is an issue commonly seen in adolescents, a group already facing increased risk for stress-related disorders. This review of current literature reveals that gestational stress exposure, as well as variations in maternal care during postnatal development, cause latent effects on the epigenome, specifically impacting the glucocorticoid receptors (GRs) encoded by the NR3C1 gene. GRs bind to glucocorticoids to regulate the body’s neuroendocrine stress response. However, in those with a history of ELA, the number of GRs is reduced, generating dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis. Rodent studies are utilized as a translational model of reference since their first weeks postnatal mimic the prenatal window of humans. That said, the details of the DNA methylation pattern at the NR3C1 gene varies, depending on species of rodent, ELA exposure, sex, and age, but there are broad similarities. Overall, due to early life adversity, data shows that epigenomic alterations in the NR3C1 gene produce HPA axis dysregulation which contributes to chronic stress and psychiatric disorders later in life.
