title: Altered neural processing of threat in alcohol-dependent men.
abstract: BACKGROUND
  Stress-response biological systems are altered in alcohol-dependent individuals and are reported to predict future relapse. This study was designed to assess neural disruptions in alcohol-dependent participants when exposed to a conditioned stimulus (CS) warning of the impending onset of a universal, nonpersonalized stressor.
  
  
  METHODS
  Fifteen alcohol-dependent men abstinent for 3 to 5 weeks and 15 age- and race-similar healthy controls were studied. Anticipatory anxiety was induced by a CS paired with an uncertain, physically painful unconditioned stressor. Neural response was assessed using functional magnetic resonance imaging.
  
  
  RESULTS
  Both groups experienced significant, similar levels of anticipatory anxiety in response to the high-threat relative to the low-threat CS. Whereas control participants markedly increased the blood oxygen level-dependent (BOLD) amplitude in cortical-limbic-striatal regions during the high-threat, relative to low-threat, stimulus, alcohol-dependent participants decreased BOLD amplitude in the pregenual anterior cingulate cortex (pgACC), medial prefrontal cortex (mPFC), medial orbitofrontal cortex, posterior cingulate cortex (PCC), bilateral parietal/occipital cortex, and right hippocampus. Alcohol-dependent participants significantly deactivated pgACC/mPFC and PCC clusters, relative to controls, during the high- versus low-threat stimulus. This difference was due to a decrease in %BOLD amplitude during the high-threat stimulus in the alcohol-dependent, but not the control, participants.
  
  
  CONCLUSIONS
  Alcohol-dependent men show cortical-limbic-striatal deactivation during anticipatory anxiety, particularly in regions associated with emotional regulation. These findings suggest a lack of engagement of affective regulatory mechanisms during high-stress situations in alcohol-dependent men.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Devous
authors.forename: Richard W
authors.initials: RW
authors.lastname: Briggs
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Spence
authors.forename: Hong
authors.initials: H
authors.lastname: Xiao
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kreyling
authors.forename: Bryon
authors.initials: B
authors.lastname: Adinoff
mesh_terms: D000437:Alcoholism / Q000503:physiopathology* / Q000523:psychology; D059031:Anticipation, Psychological; D001007:Anxiety / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology; D004644:Emotions; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008032:Limbic System / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D013315:Stress, Psychological
keywords: Alcoholism; Anticipatory Anxiety; Emotional Stress; Functional Magnetic Resonance Imaging; Striatal-Limbic-Cortical System
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