title: Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk.
abstract: OBJECTIVE
  Alcohol dependence is a chronic relapsing illness; stress, alcohol-related cues, and neutral-relaxing states significantly influence craving and relapse risk. However, neural mechanisms underlying the association between these states and alcohol craving and relapse risk remain unclear.
  
  
  OBJECTIVE
  To identify neural correlates associated with alcohol craving and relapse outcomes in 45 treatment-engaged, 4- to 8-week abstinent alcohol-dependent (AD) patients, and to compare brain responses of 30 demographically matched AD patients and 30 healthy control subjects during stress, alcohol, and neutral-relaxing cues.
  
  
  METHODS
  Functional magnetic resonance imaging study while participants were engaging in brief individualized script-driven imagery trials of stress, alcohol cues, and neutral-relaxing scenarios, and a prospective clinical outcome design to assess alcohol relapse 90 days postdischarge from inpatient treatment in the AD group.
  
  
  METHODS
  Inpatient treatment setting in a community mental health center and hospital-based research unit.
  
  
  METHODS
  Forty-five recovering AD patients in inpatient treatment for examining relapse, and 30 healthy control subjects demographically matched to 30 AD patients (subgroup of the relapse sample) for group comparisons.
  
  
  METHODS
  Twelve-step recovery-based addiction treatment for the patient group.
  
  
  METHODS
  Brain response, alcohol craving, and relapse outcome measures (time to relapse and relapse severity).
  
  
  RESULTS
  Increased ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) activation during neutral-relaxing trials was correlated with high alcohol cue-induced and stress-induced craving in early recovering AD patients (x = 6, y = 43, z = -6; P < .01, whole-brain corrected). This vmPFC/ACC hyperactivity significantly predicted subsequent alcohol relapse, with a hazards ratio greater than 8 for increased relapse risk. Additionally, vmPFC/ACC hyperactivation during neutral trials and reduced activity during stress trials were each predictive of greater days of alcohol used after relapse (P < .01, whole-brain corrected). In contrast, matched control subjects showed the reverse pattern of vmPFC/ACC responses to stress, alcohol cues, and relaxed trials (F = 6.42; P < .01, whole-brain corrected).
  
  
  CONCLUSIONS
  Findings indicate that disrupted vmPFC/ACC function plays a role in jeopardizing recovery from alcoholism and may serve as a neural marker to identify those at risk for alcohol relapse.
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA.
authors: Dongju
authors: D
authors: Seo
authors: Cheryl M
authors: CM
authors: Lacadie
authors: Keri
authors: K
authors: Tuit
authors: Kwang-Ik
authors: KI
authors: Hong
authors: R Todd
authors: RT
authors: Constable
authors: Rajita
authors: R
authors: Sinha
mesh_terms: D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000503:physiopathology* / Q000523:psychology*; D016739:Behavior, Addictive / Q000503:physiopathology*; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000503:physiopathology; D003463:Cues; D005260:Female; D059907:Functional Neuroimaging / Q000523:psychology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012008:Recurrence
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