title: Increased pro-inflammatory milieu in combat related PTSD - A new cohort replication study.
abstract: BACKGROUND
  Several lines of evidence indicate that increased inflammation is associated with Post-Traumatic Stress Disorder (PTSD). We have previously reported that peripheral inflammatory markers are significantly higher in combat-exposed veterans with than without PTSD. This study was designed to replicate these findings in a new study cohort using the same population and recruitment strategies.
  
  
  METHODS
  Sixty-one male war veterans (31 PTSD and 30 control subjects) were included in this replication study. Levels of Interleukin-6, Tumor Necrosis Factor-alpha, Gamma interferon, and high-sensitivity C-reactive protein were quantified in blood samples. A standardized "total pro-inflammatory score" was calculated to limit the number of statistical comparisons. The Clinician Administered PTSD Scale (CAPS) rating scale was used to assess PTSD symptom severity.
  
  
  RESULTS
  PTSD subjects had significantly higher total pro-inflammatory scores compared to non-PTSD subjects in unadjusted analysis (Cohen's d=0.75, p=0.005) as well as after adjusting for potentially confounding effects of age, BMI, smoking, and potentially interfering medications and somatic co-morbidities (p=0.023). There were no significant correlations between inflammatory markers and severity of symptoms within the PTSD group.
  
  
  CONCLUSIONS
  We replicated, in a new sample, our previous finding of increased inflammatory markers in combat-exposed PTSD subjects compared to combat-exposed non-PTSD controls. These findings strongly add to the growing literature suggesting that immune activation may be an important aspect of PTSD pathophysiology, although not directly correlated with current PTSD symptom levels in the PTSD group.
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Psychiatry, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Sylvester Comprehensive Cancer Center, University of Miami, FL, United States.
authors.forename: Firdaus S
authors.initials: FS
authors.lastname: Dhabhar
authors.affiliation: Department of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Synthia H
authors.initials: SH
authors.lastname: Mellon
authors.affiliation: James J. Peters Veterans Administration Medical Center Bronx, New York, United States; Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yehuda
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA, United States; Department of Surgery, Veterans Affairs Medical Center, San Francisco, CA, United States.
authors.forename: S Marlene
authors.initials: SM
authors.lastname: Grenon
authors.affiliation: James J. Peters Veterans Administration Medical Center Bronx, New York, United States; Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Janine D
authors.initials: JD
authors.lastname: Flory
authors.affiliation: James J. Peters Veterans Administration Medical Center Bronx, New York, United States; Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Bierer
authors.affiliation: Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and Traumatic Brain Injury, Department of Psychiatry, NYU, New York, United States.
authors.forename: Duna
authors.initials: D
authors.lastname: Abu-Amara
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Coy
authors.affiliation: James J. Peters Veterans Administration Medical Center Bronx, New York, United States; Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Iouri
authors.initials: I
authors.lastname: Makotkine
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Reus
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: F Saverio
authors.initials: FS
authors.lastname: Bersani
authors.affiliation: Steven and Alexandra Cohen Veterans Center for Posttraumatic Stress and Traumatic Brain Injury, Department of Psychiatry, NYU, New York, United States. Electronic address: Charles.Marmar@nyumc.org.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Marmar
authors.affiliation: Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States. Electronic address: Owen.Wolkowitz@ucsf.edu.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Wolkowitz
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003130:Combat Disorders / Q000097:blood; D016207:Cytokines / Q000097:blood; D039721:Diagnostic and Statistical Manual of Mental Disorders; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology*; D008297:Male; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000473:pathology* / Q000523:psychology; D014728:Veterans
chemical_list: D016207:Cytokines
keywords: Combat; Cytokines; Depression; Inflammation; Post-Traumatic Stress Disorder (PTSD)