title: Associations between the self-reported frequency of hearing chemical alarms in theater and regional brain volume in Gulf War Veterans.
abstract: BACKGROUND
  We previously reported evidence of reduced cortical gray matter (GM), white matter (WM), and hippocampal volume in Gulf War (GW) veterans with predicted exposure to low-levels of nerve agent according to the 2000 Khamisiyah plume model analysis. Because there is suggestive evidence that other nerve agent exposures may have occurred during the Gulf War, we examined the association between the self-reported frequency of hearing chemical alarms sound during deployment in the Gulf War and regional brain volume in GW veterans.
  
  
  METHODS
  Ninety consecutive GW veterans (15 female, mean age: 52±8years) participating in a VA-funded study underwent structural magnetic resonance imaging (MRI) on a 3T scanner. Freesurfer (version 5.1) was used to obtain regional measures of cortical GM, WM, hippocampal, and insula volume. Multiple linear regression was used to determine the association between the self-reported frequencies of hearing chemical alarms during the Gulf War and regional brain volume.
  
  
  RESULTS
  There was an inverse association between the self-reported frequency of hearing chemical alarms sound and total cortical GM (adjusted p=0.007), even after accounting for potentially confounding demographic and clinical variables, the veterans' current health status, and other concurrent deployment-related exposures that were correlated with hearing chemical alarms. Post-hoc analyses extended the inverse relationship between the frequency of hearing chemical alarms to GM volume in the frontal (adjusted p=0.02), parietal (adjusted p=0.01), and occipital (adjusted p=0.001) lobes. In contrast, regional brain volumes were not significantly associated with predicted exposure to the Khamisiyah plume or with Gulf War Illness status defined by the Kansas or Centers for Disease Control and Prevention criteria.
  
  
  CONCLUSIONS
  Many veterans reported hearing chemical alarms sound during the Gulf War. The current findings suggest that exposure to substances that triggered those chemical alarms during the Gulf War likely had adverse neuroanatomical effects.
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States; Department of Psychiatry, University of California San Francisco, San Francisco, CA, United States. Electronic address: linda.chao@ucsf.edu.
authors.forename: Linda L
authors.initials: LL
authors.lastname: Chao
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Reeb
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States.
authors.forename: Iva L
authors.initials: IL
authors.lastname: Esparza
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 114M, San Francisco, CA 94121, United States.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Abadjian
mesh_terms: D000328:Adult; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D047830:Gulf War; D034381:Hearing Loss / Q000453:epidemiology* / Q000209:etiology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018923:Persian Gulf Syndrome / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D057566:Self Report; D058014:Veterans Health
chemical_list: D053327:Apolipoprotein E4
keywords: Brain imaging; Cerebral volume; Chemical warfare agents; Gulf War veterans