title: Glucocorticoid sensitivity of leukocytes predicts PTSD, depressive and fatigue symptoms after military deployment: A prospective study.
abstract: OBJECTIVE
  Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and severe fatigue may develop in response to severe stress and trauma. These conditions have all been shown to be associated with altered sensitivity of leukocytes for regulation by glucocorticoids (GCs). However, it remains unknown whether sensitivity of leukocytes for GCs is a pre-existing vulnerability factor, or whether GC-sensitivity of leukocytes alters as a consequence of stress and stress-related conditions. Our aim was to investigate whether sensitivity of T-cells and monocytes for regulation by GCs (i.e. dexamethasone: DEX) assessed before military deployment predicts high levels of PTSD, depressive, and/or fatigue symptoms 6 months after return from deployment.
  
  
  METHODS
  We included 526 male military personnel before deployment to Afghanistan. Logistic regression analysis was performed to predict fatigue, depressive, and PTSD symptoms 6 months after deployment based on sensitivity of LPS-induced TNF-α production and PHA-induced T-cell proliferation to DEX-inhibition before deployment.
  
  
  RESULTS
  Severe fatigue 6 months after deployment was independently associated with low DEX-sensitivity of monocyte TNF-α production before deployment. A high level of depressive symptoms after deployment was independently associated with a low DEX-sensitivity of T-cell proliferation. In contrast, a high level of PTSD symptoms after deployment was independently associated with a high DEX-sensitivity of T-cell proliferation before deployment, but only in individuals who reported PTSD symptoms without depressive symptoms. The predictive value of DEX-sensitivity was independent of childhood trauma and GR number, GR subtype and GR target gene mRNA expression in leukocytes.
  
  
  CONCLUSIONS
  We present here for the first time that the sensitivity of leukocytes for GCs prior to deployment is a predictive factor for the development of PTSD, depressive and fatigue symptomatology in response to deployment. Notably, PTSD, depressive and fatigue symptoms were differentially associated with GC-sensitivity of monocytes and T-cells and therefore may have different biological underpinnings.
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Zuiden
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Mirjam
authors.initials: M
authors.lastname: Maas
authors.forename: Karima
authors.initials: K
authors.lastname: Amarouchi
authors.forename: Eric
authors.initials: E
authors.lastname: Vermetten
authors.forename: Elbert
authors.initials: E
authors.lastname: Geuze
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D003863:Depression / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D003907:Dexamethasone / Q000276:immunology / Q000494:pharmacology; D005221:Fatigue / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D005938:Glucocorticoids / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008889:Military Personnel / Q000523:psychology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011965:Receptors, Glucocorticoid / Q000032:analysis; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D011795:Surveys and Questionnaires; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone