Early environmental influences on the development of children's brain structure and function

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

To briefly review results of the latest research on the contributions of depression, anxiety, and stress exposures in pregnancy to adverse maternal and child outcomes, and to direct attention to new findings on pregnancy anxiety, a potent maternal risk factor. Anxiety, depression, and stress in pregnancy are risk factors for adverse outcomes for mothers and children. Anxiety in pregnancy is associated with shorter gestation and has adverse implications for fetal neurodevelopment and child outcomes. Anxiety about a particular pregnancy is especially potent. Chronic strain, exposure to racism, and depressive symptoms in mothers during pregnancy are associated with lower birth weight infants with consequences for infant development. These distinguishable risk factors and related pathways to distinct birth outcomes merit further investigation. This body of evidence, and the developing consensus regarding biological and behavioral mechanisms, sets the stage for a next era of psychiatric and collaborative interdisciplinary research on pregnancy to reduce the burden of maternal stress, depression, and anxiety in the perinatal period. It is critical to identify the signs, symptoms, and diagnostic thresholds that warrant prenatal intervention and to develop efficient, effective and ecologically valid screening and intervention strategies to be used widely.

Variations in phenotype reflect the influence of environmental conditions during development on cellular functions, including that of the genome. The recent integration of epigenetics into developmental psychobiology illustrates the processes by which environmental conditions in early life structurally alter DNA, providing a physical basis for the influence of the perinatal environmental signals on phenotype over the life of the individual. This review focuses on the enduring effects of naturally occurring variations in maternal care on gene expression and phenotype to provide an example of environmentally driven plasticity at the level of the DNA, revealing the interdependence of gene and environmental in the regulation of phenotype.