title: Cytokine production as a putative biological mechanism underlying stress sensitization in high combat exposed soldiers.
abstract: OBJECTIVE
  Combat stress exposed soldiers may respond to post-deployment stressful life events (SLE) with increases in symptoms of posttraumatic stress disorder (PTSD), consistent with a model of stress sensitization. Several lines of research point to sensitization as a model to describe the relations between exposure to traumatic events, subsequent SLE, and symptoms of PTSD. Based on previous findings we hypothesized that immune activation, measured as a high in vitro capacity of leukocytes to produce cytokines upon stimulation, underlies stress sensitization.
  
  
  METHODS
  We assessed mitogen-induced cytokine production at 1 month, SLE at 1 year, and PTSD symptoms from 1 month up to 2 years post-deployment in soldiers returned from deployment to Afghanistan (N=693). Exploratory structural equation modeling as well as latent growth models were applied.
  
  
  RESULTS
  The data demonstrated significant three-way interaction effects of combat stress exposure, cytokine production, and post-deployment SLE on linear change in PTSD symptoms over the first 2 years following return from deployment. In soldiers reporting high combat stress exposure, both high mitogen-stimulated T-cell cytokine production and high innate cytokine production were associated with increases in PTSD symptoms in response to post-deployment SLE. In low combat stress exposed soldiers as well as those with low cytokine production, post-deployment SLE were not associated with increases in PTSD symptoms.
  
  
  CONCLUSIONS
  High stimulated T-cell and innate cytokine production may contribute to stress sensitization in recently deployed, high combat stress exposed soldiers. These findings suggest that detecting and eventually normalizing immune activation may potentially complement future strategies to prevent progression of PTSD symptoms following return from deployment.
authors.affiliation: Foundation Centrum '45/Arq, Diemen, The Netherlands. Electronic address: g.smid@centrum45.nl.
authors.forename: Geert E
authors.initials: GE
authors.lastname: Smid
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Zuiden
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: Laboratory of Neuroimmunology of Cancer-Related Symptoms (NICRS), The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.affiliation: Laboratory of Neuroimmunology of Cancer-Related Symptoms (NICRS), The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.affiliation: Foundation Centrum '45/Arq, Diemen, The Netherlands; 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; Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Vermetten
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D003130:Combat Disorders / Q000175:diagnosis / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D008016:Life Change Events; D008875:Middle Aged; D008889:Military Personnel / Q000523:psychology*; D008962:Models, Theoretical; D009426:Netherlands; D011446:Prospective Studies; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis / Q000378:metabolism*; D013315:Stress, Psychological / Q000175:diagnosis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Chemokines; Cytokines; Military; Posttraumatic stress disorder; Stress sensitization