Differential effects of DRN GR deletion in female mice may provide insight into the greater incidence of depression and specific depression symptoms in women.
In the context of environmental stress, a functional variant in the glucocorticoid receptor co-chaperone FKBP5 gene has been repeatedly shown to increase risk for psychiatric illness, including depression.
In a cross-sectional genetic association study of 526 white outpatients with chronic coronary heart disease, we examined whether haplotypes of the glucocorticoid receptor gene (NR3C1) are associated with depression.
In addition, GR and corticotropin-releasing hormone receptor 1 (CRHR1) genotypes contributed significantly to psychosis measures and CRHR1 contributed significantly to depression severity rating.
Pain and depressive-like behavior were measured over 14 days and brain-derived neurotrophic factor (BDNF; a factor involved in nociception and depression) and glucocorticoid receptor (GR; a stress-related receptor) expression were measured on day 14.
Polymorphisms in the FK506 binding protein 5 (FKBP5) gene have been shown to influence glucocorticoid receptor sensitivity, stress response regulation, and depression risk in traumatized subjects, with most consistent findings reported for the functional variant rs1360780.
We found association between the diagnosis of depression and DNA sequence variants in intron 2 as well as in the 5' region of the NR3C1 gene but not for the previously studied exon 2 and putative promoter variants (global test after control of multiple testing, P = 0.02).
Allelic variants of the glucocorticoid receptor (GR) gene contribute significantly to both cortisol levels and to measures of psychosis; corticotropin-releasing hormone receptor 1 variants contribute to measures of depression and psychosis.
Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain.
Therefore, the interaction of two polymorphisms, one on the cholinergic CHRNA4 receptor gene and one on the glucocorticoid receptor gene (NR3C1), on depression was investigated.
Recent human studies show that DNA methylation changes of hypothesis-driven candidate gene regions, such as the promoter of the glucocorticoid receptor and the serotonin transporter, were associated with maternal depression in peripheral tissue samples of newborns' cord blood, infants' saliva, or adults' peripheral blood.
In association studies, increased susceptibility to depression has been noted in those with polymorphisms in the following: D-amino-acid-oxidase activator/G30 gene complex, glucocorticoid receptor gene, serotonin transporter gene, tryptophan hydroxylase 2 gene, dopamine transporter gene and G protein-coupled receptor 50 gene.
Haplotypic variation in the regulatory region of the NR3C1 may increase vulnerability to depressive disorders requiring hospital admission, but is not associated with self-reported symptoms.
In this study, we tested the leukocyte mRNA expression levels of genes belonging to glucocorticoid receptor (GR) function (FKBP-4, FKBP-5, and GR), inflammation (interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-7, IL-8, IL-10, macrophage inhibiting factor (MIF), and tumor necrosis factor (TNF)-α), and neuroplasticity (brain-derived neurotrophic factor (BDNF), p11 and VGF), in healthy controls (n=34) and depressed patients (n=74), before and after 8 weeks of treatment with escitalopram or nortriptyline, as part of the Genome-based Therapeutic Drugs for Depression study.
Glucocorticoid receptor dysfunction orchestrates inflammasome effects on chronic obstructive pulmonary disease-induced depression: A potential mechanism underlying the cross talk between lung and brain.