title: Pre-deployment differences in glucocorticoid sensitivity of leukocytes in soldiers developing symptoms of PTSD, depression or fatigue persist after return from military deployment.
abstract: Deployed soldiers are at risk of developing stress-related conditions, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and severe fatigue. We previously observed condition- and cell-specific differences in sensitivity of immune cells for regulation by glucocorticoids (GCs) pre-deployment between male soldiers with and without subsequent development of high levels of these stress-related symptoms. Here we investigated whether these pre-deployment dysregulations in GC-sensitivity of immune cells persisted after return from military deployment. In a prospective, longitudinal study including 721 male and female soldiers, the in vitro GC-sensitivity of monocytes and T-cells was assessed prior to deployment and one and six months post-deployment. Differences in the longitudinal course of sensitivity for regulation by dexamethasone (DEX) of LPS-stimulated TNF-α production and PHA-stimulated T-cell proliferation between soldiers with and without subsequent symptom development were investigated using linear mixed models. Within the whole group, DEX-sensitivity of monocytes was significantly decreased at six months post-deployment compared to the assessments pre-deployment and one month post-deployment. The DEX-sensitivity of T-cells did not significantly change over time. Participants developing high levels of PTSD symptoms showed high DEX-sensitivity of T-cells, while participants developing high levels of depressive symptoms showed low DEX-sensitivity of T-cells before deployment that persisted at the two time points after return. In addition, participants developing severe fatigue had low DEX-sensitivity of monocytes at all assessments. Our finding that the previously observed pre-deployment group differences in peripheral GC-sensitivity persisted until at least six months after return indicates that in vitro GC-sensitivity of T-cells and monocytes may represent a persistent biological vulnerability factor for development of stress-related conditions PTSD, depression and fatigue.
authors.affiliation: Center for Psychotrauma, Department of Psychiatry, Anxiety Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.vanzuiden@amc.nl.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Zuiden
authors.affiliation: Neuroimmunology Laboratory, Department of Symptom Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.affiliation: Research Centre Military Mental Health, Ministry of Defense, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands; Arq Psychotrauma Expert Group, Diemen, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Vermetten
authors.affiliation: Center for Psychotrauma, Department of Psychiatry, Anxiety Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Arq Psychotrauma Expert Group, Diemen, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: Olff
authors.affiliation: Research Centre Military Mental Health, Ministry of Defense, Utrecht, The Netherlands; Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Elbert
authors.initials: E
authors.lastname: Geuze
authors.affiliation: Neuroimmunology Laboratory, Department of Symptom Research, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cobi
authors.initials: C
authors.lastname: Heijnen
mesh_terms: D000293:Adolescent; D000328:Adult; D003863:Depression / Q000175:diagnosis* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005221:Fatigue / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008889:Military Personnel; D009000:Monocytes / Q000187:drug effects*; D011446:Prospective Studies; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone
keywords: Combat; Depression; Fatigue; Glucocorticoid receptor; PTSD; Stress