Increased methylation at an unexplored glucocorticoid responsive element within exon 1D of NR3C1 gene is related to anxious-depressive disorders and decreased hippocampal connectivity.

摘要: Among the major psychiatric disorders, anxious-depressive disorders stand out as one of more prevalent and frequently associated with hypothalamic-pituitary-adrenal (HPA) axis abnormalities. Methylation at exon 1F glucocorticoid receptor gene NR3C1 has been both early stress exposure risk for developing a disorder; however, other promoter regions have underexplored. Exon 1D emerges suggestive new target in stress-related epigenetically sensitive to adversity. After assessment 48 monozygotic twin pairs (n=96 subjects) informative lifetime history they were classified concordant, discordant or healthy function whether both, neither each pair had diagnosis disorders. DNA epigenetic analysis was extracted from peripheral blood. CpG-specific methylation analysed by means pyrosequencing technology. Functional magnetic resonance imaging available 54 subjects (n=27 pairs). within responsive element (GRE) correlated familial burden (r=0.35, z=2.26, p=0.02). Right hippocampal connectivity significantly GRE (β=-2.33, t=-2.85, p=0.01). uniformly hypomethylated across all subgroups present sample. hypermethylation twins concordant suggests this region plays role increasing vulnerability psychosocial stress, partly mediated altered connectivity.