title: An investigation of vago-regulatory and health-behavior accounts for increased inflammation in posttraumatic stress disorder.
abstract: OBJECTIVE
  Posttraumatic stress disorder (PTSD) has been linked to chronic inflammation, a condition that poses a risk for cardiovascular disease. Attenuated vagal activity has been proposed as a potential mediator of PTSD and inflammation, although associated behavioral health risks-namely cigarette smoking and alcohol dependence-might also account for that link.
  
  
  METHODS
  Inflammation was quantified by fasting serum concentrations of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-10, and thymus- and activation-regulated chemokine (TARC)/CCL17 collected from 85 participants with PTSD and 82 without PTSD. Latent variable modeling was used to assess the relationship between PTSD symptom severity and inflammation along with potential mediators vagal activity (respiratory sinus arrhythmia; RSA), smoking status, and lifetime alcohol dependence.
  
  
  RESULTS
  PTSD symptom severity was associated with increased inflammation (β=.18, p=.02). However, this association was reduced in models that adjusted for RSA, smoking status, and lifetime alcohol dependence. Independent mediation effects were deemed significant via bootstrapping analyses. Together, RSA, smoking status, and lifetime alcohol dependence accounted for 95% of the effect of PTSD symptom severity on inflammation.
  
  
  CONCLUSIONS
  Although RSA accounted for a modest proportion of the association between posttraumatic stress and pro-inflammatory responses, behavioral factors-specifically cigarette smoking and alcohol dependence-proved to be larger mediators. The benefits of PTSD treatment may be enhanced by additional interventions aimed at modifying these health behaviors.
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA. Electronic address: paul.dennis2@va.gov.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dennis
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC 27705, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA; Veterans Affairs Mid-Atlantic Region Mental Illness Research, Education, and Clinical Center, Durham, NC 27705, USA; Veterans Affairs Center for Health Services Research in Primary Care, Durham, NC 27705, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Calhoun
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Lana L
authors.initials: LL
authors.lastname: Watkins
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sherwood
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Michelle F
authors.initials: MF
authors.lastname: Dennis
authors.affiliation: Durham Veterans Affairs Medical Center, Durham, NC 27705, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA; Veterans Affairs Mid-Atlantic Region Mental Illness Research, Education, and Clinical Center, Durham, NC 27705, USA.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Beckham
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications*; D002097:C-Reactive Protein / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D015438:Health Behavior; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology* / Q000523:psychology*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*; D013313:Stress Disorders, Post-Traumatic / Q000150:complications* / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014630:Vagus Nerve / Q000503:physiopathology*
chemical_list: C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein
keywords: Alcohol dependence; Cigarette smoking; Cytokines; Inflammation; Posttraumatic stress disorder; Vagal tone