GR-mediated FKBP5 RNA induction differentially influenced by weight in major depression and healthy controls

Abstract

Background: The FK 506 binding protein 51 or FKBP5 has been implicated in the regulation of the glucocorticoid receptor (GR) sensitivity, especially in major depression and posttraumatic stress disorder. Additionally, the weight of study participants has been associated with FKBP5 mediated endocrine alterations, we wanted to characterize GR sensitivity in healthy volunteers and depressed patients in dependence of weight. Methods: FKBP5 mRNA expression (baseline and following in vivo GR-stimulation with 1.5 mg dexamethasone p.o.) was analyzed together with plasma cortisol, ACTH, and BMI in 50 depressed patients and 85 controls (44%/42% obese participants with a body mass index (BMI)> 25). To evaluate the function of the HPA-axis, we employed the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test. Results: No baseline differences in FKBP5 mRNA expression were observed, but controls with BMI> 25 showed less induction of FKBP5 mRNA expression following dexamethasone stimulation (p = 0.03). In addition, ACTH levels in obese healthy participants were significant higher (p = 0.04), and cortisol levels were higher in obese depressed patients (p = 0.009). The cortisol suppression as readout of the dex-CRH test was enhanced in obese controls (p = 0.04). Conclusions: Owe found substantial differences in the response to GR activation influenced by the weight of participants, which affect the HPA axis regulation. Overweight might be associated with an impaired GR sensitivity.