title: Altered inflammatory activity associated with reduced hippocampal volume and more severe posttraumatic stress symptoms in Gulf War veterans.
abstract: BACKGROUND
  Inflammation may reduce hippocampal volume by blocking neurogenesis and promoting neurodegeneration. Posttraumatic stress disorder (PTSD) has been linked with both elevated inflammation and reduced hippocampal volume. However, few studies have examined associations between inflammatory markers and hippocampal volume, and none have examined these associations in the context of PTSD.
  
  
  METHODS
  We measured levels of the inflammatory markers interleukin-6 (IL-6) and soluble receptor II for tumor necrosis factor (sTNF-RII) as well as hippocampal volume in 246 Gulf War veterans with and without current and past PTSD as assessed with the Clinician Administered PTSD Scale (CAPS). Enzyme-linked immunosorbent assays were used to measure inflammatory markers, and 1.5Tesla magnetic resonance imaging (MRI) and Freesurfer version 4.5 were used to quantify hippocampal volume. Hierarchical linear regression and analysis of covariance models were used to examine if hippocampal volume and PTSD status would be associated with elevated levels of IL-6 and sTNF-RII.
  
  
  RESULTS
  Increased sTNF-RII, but not IL-6, was significantly associated with reduced hippocampal volume (β=-0.14, p=0.01). The relationship between sTNF-RII and hippocampal volume was independent of potential confounds and covariates, including PTSD status. Although we observed no PTSD diagnosis-related differences in either IL-6 or sTNF-RII, higher PTSD severity was associated with significantly increased sTNF-RII (β=0.24, p=0.04) and reduced IL-6 levels (β=-0.24, p=0.04).
  
  
  CONCLUSIONS
  Our results indicate that specific inflammatory proteins may be associated with brain structure and function as indexed by hippocampal volume and PTSD symptoms.
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA. Electronic address: Aoife.ODonovan@ucsf.edu.
authors.forename: Aoife
authors.initials: A
authors.lastname: O'Donovan
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Chao
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA; California School of Professional Psychology at Alliant International University, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Paulson
authors.affiliation: San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA; California School of Professional Psychology at Alliant International University, USA.
authors.forename: Kristin W
authors.initials: KW
authors.lastname: Samuelson
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Judy K
authors.initials: JK
authors.lastname: Shigenaga
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Mike W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: University of California, San Francisco, CA, USA; San Francisco Veteran's Affairs Medical Center and Northern California Institute for Research and Education, San Francisco, CA, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Neylan
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D047830:Gulf War; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D014728:Veterans / Q000523:psychology*
chemical_list: D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II
keywords: Hippocampus; Inflammation; Posttraumatic stress disorder; Structural magnetic resonance imaging; Trauma; Veterans