Many decades of research in rodents, Hexamethonium Bromide non-human primates, and humans have documented the impact of early experiences on the neurobiological mechanisms regulating stress responses and mood and anxiety disorders. Young children are dependent on caregivers for their basic physical, social and emotional needs, and in addition undergo substantial developmental changes in neural pathways involved in regulating emotion and behavior. As a result, disruption of early care-giving can produce profound and long-lasting changes in these neurobiological and behavioral systems. Early-life stress is a risk factor for major depression, post-traumatic stress disorder, and drug abuse, among other conditions. Alteration of basal and stress-induced activity of the hypothalamic-pituitary-adrenal axis is implicated in the pathogenesis of these disorders. Chronic alterations of HPA axis activity have been shown in rodents and non-human primates exposed to disruptions of parental care such as maternal separation and maternal neglect, and in humans with childhood parental loss, and neglect or other forms of childhood maltreatment. Elevated glucocorticoids impair neuronal growth and survival, diminish neurotrophins and modify immune function, and accelerate cellular aging, all of which have been associated with both early-life stress and major depression. Preclinical work implicates epigenetic changes to the gene for the type II glucocorticoid receptor as a mechanism underlying the neuroendocrine effects of environmental adversity. Epigenetic alterations to DNA influence gene expression but do not change the nucleotide sequence of DNA. Sulconazole Nitrate methylation is a stable form of epigenetic modification which alters gene expression via effects on transcription factor binding. Methyl residues chemically modify regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide via a phosphodiester bond. As reviewed by Weaver and Champagne and Curley, low levels of maternal care in rodents result in greater methylation of the promoter region of the hippocampal glucocorticoid receptor gene, which interferes with binding of nerve growth factor inducible protein A, a transcription factor. Greater methylation reduces NR3C1 gene expression, which results in decreased numbers of GRs in the hippocampus and exaggerated hormonal and behavioral sequelae of stress. Two published investigations have examined associations of early experiences with epigenetic modification of the promoter of the human GR gene NR3C1. Both studies focused on the exon 1F region of the promoter, which is homologous to the rat exon 17 and contains the NGFI-A binding site. Oberlander and colleagues examined mixed mononuclear cells from cord blood of 82 infants and found that increased maternal depressed mood in the third trimester was linked to increased methylation at CpG 1 and 2 in this region, as well as CpG 3, an NGFI-A binding site.