Recent evidence has suggested that impaired glucocorticoid receptor (GR), the signaling of key molecules of the HPA axis, plays a key role in the behavioral and neuroendorcrine alterations of major depression.
After conservative correction of Type-I-error to obtain reliable p values, one SNP in the NR3C1 gene, namely rs6195, showed a significant association with the presence of a major depression (p = 0.048) in females.
Aim Based on the AGENDA trial dataset, we analysed whether an intervention with SSRI versus placebo decreases the GRα mRNA expression in peripheral blood cells in healthy first-degree relatives of patients with major depression.
Fifty-nine depressed individuals with major depressive disorder (n=33) or bipolar disorder (n=26), and 32 healthy individuals were genotyped for the glucocorticoid receptor BclI G/C polymorphism, and underwent functional magnetic resonance imaging during a monetary reward task.
Taken together, these results indicate that CDK5 is an integral component of stress response and major depression with regulatory means specific to different stressors, brain areas and diseases in part through changing phosphorylation of GR.
Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder.
Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder.
Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation.
Therefore, we investigated if polymorphism of the glucocorticoid receptor gene (NR3C1), involved in the regulation of HPA axis, may alter susceptibility as well as the course of major depressive disorder and bipolar disorder.
In this overview, currently known clinically relevant GR and MR polymorphisms are discussed in relation to mood disorders (both unipolar depression and bipolar disorder) and cognitive function.
Perturbations in HPA axis sensitivity to glucocorticoids implicated in the pathogenesis of major depression may result from functional alterations in the glucocorticoid receptor gene.