title: Determinants of altered intracellular endocrine-immune interplay in Bosnian war refugees suffering from PTSD.
abstract: Posttraumatic Stress Disorder (PTSD) has been repeatedly linked to changes in glucocorticoid (GC) sensitivity. To increase our understanding of this phenomenon and its potential relevance for PTSD development and treatment, the current study investigates the interplay between two key moderators, glucocorticoid receptor (GRα) and GR co-chaperone FKBP5, and their relation to GC sensitivity. A GC sensitivity assay was performed in 52 Bosnian war refugees (19m; 40.8±8.7 years) clinically diagnosed with PTSD to divide the patient group into a high (HS) and a low (LS) GC sensitivity group. Expression of GRα and FKBP5 mRNA was quantified by real-time RT-PCR. Links between gene expression and GC sensitivity were driven by the HS group of PTSD patients, which also showed increased expression of GRα but not FKBP5 compared to the LS group. Further, expressions of FKBP5 and GRα were strongly correlated in the HS patient group, while this association was missing in the LS PTSD group. Our findings suggest that PTSD phenotypes may be characterized by differences in intracellular signaling transduction processes. The associations of expression of GRα and FKBP5 in the high-sensitive PTSD subgroup may thereby reflect physiological adaptation to preserve immune-relevant GC signaling. Further research is needed to understand the role and consequences of GRα-FKBP5 dissociation in low GC sensitivity PTSD patients.
authors.affiliation: Brandeis University, Waltham, MA 02453, USA.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Pitts
authors.affiliation: LVR-Klinikum Düsseldorf, 40629 Düsseldorf, Germany.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Joksimovic
authors.affiliation: Technische Universität Dresden, Dresden, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Steudte-Schmiedgen
authors.affiliation: Brandeis University, Waltham, MA 02453, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rohleder
authors.affiliation: Brandeis University, Waltham, MA 02453, USA. Electronic address: jmw@brandeis.edu.
authors.forename: Jutta M
authors.initials: JM
authors.lastname: Wolf
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D017522:Bosnia and Herzegovina / Q000208:ethnology; D016022:Case-Control Studies; D005260:Female; D005858:Germany; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000097:blood*; D012036:Refugees / Q000523:psychology*; D015398:Signal Transduction; D013313:Stress Disorders, Post-Traumatic / Q000208:ethnology / Q000276:immunology* / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000097:blood*; D000067453:War Exposure / Q000009:adverse effects*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C411470:glucocorticoid receptor alpha
keywords: Bosnian war refugees; FK506 binding protein 51; Glucocorticoid receptor; Glucocorticoid sensitivity; Posttraumatic stress disorder