Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2013-06, Vol.43, p.238-245
• Main Authors: Matić, Gordana, Milutinović, Danijela Vojnović, Nestorov, Jelena, Elaković, Ivana, Jovanović, Sanja Manitašević, Perišić, Tatjana, Dunđerski, Jadranka, Damjanović, Svetozar, Knežević, Goran, Špirić, Željko, Vermetten, Eric, Savić, Danka
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Analysis of Variance; Anxiety disorders. Neuroses; Biological and medical sciences; Blotting, Western; Dexamethasone - metabolism; Dexamethasone - pharmacology; Diagnostic and Statistical Manual of Mental Disorders; Electrophoresis, Polyacrylamide Gel; Glucocorticoid receptor; Glucocorticoids - metabolism; Hormones - metabolism; Humans; Kinetics; Lymphocytes - metabolism; Male; Medical sciences; Middle Aged; Muramidase - biosynthesis; Neuropharmacology; Peripheral blood mononuclear cells; Pharmacology. Drug treatments; Post-traumatic stress disorder; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; PTSD; Radioligand Assay; Real-Time Polymerase Chain Reaction; Receptors, Glucocorticoid - biosynthesis; Resilience to PTSD; Serbia; Stress Disorders, Post-Traumatic - metabolism; Stress Disorders, Post-Traumatic - psychology; War trauma; Warfare; Wounds and Injuries - psychology
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2013.01.005

Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD. Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting. Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (Bmax) in PBMCs. Hormone-binding potential (Bmax/KD ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between Bmax and KD that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting Bmax data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD. Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between Bmax and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs. ► PTSD is characterized by reduced lymphocyte GR hormone-binding potential. ► Compensation between GR number and hormone-binding affinity is disturbed in PTSD. ► Resilience to PTSD is associated with increased fractional occupancy of the GR.