title: Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on brain structure and function: a study at 4T.
abstract: BACKGROUND
  More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner.
  
  
  METHODS
  Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF).
  
  
  RESULTS
  Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (β=-0.11, p=0.02) and WM (β=-0.14, p=0.03) volumes, and number of CPT omission errors (β=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Multisymptom Illness on both GM and WM volume in the GB/GF exposed veterans.
  
  
  CONCLUSIONS
  These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the exposure.
authors: Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA. linda.chao@ucsf.edu
authors: Linda L
authors: LL
authors: Chao
authors: Linda
authors: L
authors: Abadjian
authors: Jennifer
authors: J
authors: Hlavin
authors: Deiter J
authors: DJ
authors: Meyerhoff
authors: Michael W
authors: MW
authors: Weiner
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002619:Chemical Warfare Agents / Q000633:toxicity*; D016009:Chi-Square Distribution; D003071:Cognition / Q000187:drug effects*; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D047830:Gulf War; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D019570:Inhalation Exposure; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D008889:Military Personnel; D009483:Neuropsychological Tests; D016273:Occupational Exposure; D009943:Organophosphorus Compounds / Q000633:toxicity*; D018923:Persian Gulf Syndrome / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D012524:Sarin / Q000633:toxicity*; D013997:Time Factors; D014481:United States; D014728:Veterans
chemical_list: D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D012524:Sarin; C053914:cyclohexyl methylphosphonofluoridate