Nonetheless, aberrant hypothalamus-pituitary-adrenal (HPA) axis activity, especially in terms of cortisol and glucocorticoid receptor (GR) alterations, has been postulated as a tenable factor in the etiology and pathophysiology of PTSD.
Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity.
Evidence that the GR may be an important therapeutic target for the treatment of PTSD, especially for functions subserved by the hippocampus, is discussed.
Specific patterns of a dysregulation of the HPA axis and GR function are found in different stress-related psychiatric entities e.g. major depression, job-related exhaustion or posttraumatic stress disorder.
The protective effects of dexamethasone on postoperative PTSD symptoms were dependent on the GR polymorphisms rs41423247 (p = .009), rs10052957 (p = .003), and rs6189 (p = .002), but not on rs6195 (p = .025) or rs6198, (p = .026) after Bonferroni correction.
Results show that genes related to the physiological stress response (e.g., glucocorticoid receptor and activity, neuroendocrine release), learning and memory (e.g., plasticity), mood, and pain perception are tied to neural intermediate phenotypes associated with PTSD.
In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD).
PTSD was associated with NR3C1 epigenetic modifications that were similarly found in the mothers and their offspring, modifications that may underlie the possible transmission of biological alterations of the HPA axis.
Reduced peripheral expression of the glucocorticoid receptor α isoform in individuals with posttraumatic stress disorder: a cumulative effect of trauma burden.
The gene encoding FK506-binding protein 51 (FKBP5), a co-chaperone of the glucocorticoid receptor (GR), has been associated with stress reactivity and PTSD risk.
Together, these findings indicate that an epigenetic modification of the glucocorticoid receptor gene promoter is linked to interindividual and gender-specific differences in memory functions and PTSD risk.
In a recent study in patients who underwent cardiac surgery, the BclI polymorphism of the glucocorticoid receptor gene (NR3C1) was associated with traumatic memories and posttraumatic stress disorder symptoms after intensive care therapy.
Several GR pathway components predicted subsequent development of a high level of PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with increased risk for a high level of PTSD symptoms.
The expression of GR gradually increased on days 1, 4, and 7, but decreased on days 14 and 28, respectively.MR and GR in the locus coeruleus may have a role in the development of long-term persistent neuropsychological sequelae in PTSD.