title: Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.
abstract: BACKGROUND
  Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism.
  
  
  OBJECTIVE
  This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy.
  
  
  METHODS
  Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task.
  
  
  RESULTS
  There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking.
  
  
  CONCLUSIONS
  These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
authors: Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA. schacht@musc.edu
authors: Joseph P
authors: JP
authors: Schacht
authors: Raymond F
authors: RF
authors: Anton
authors: Patrick K
authors: PK
authors: Randall
authors: Xingbao
authors: X
authors: Li
authors: Scott
authors: S
authors: Henderson
authors: Hugh
authors: H
authors: Myrick
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000517:prevention & control; D000437:Alcoholism / Q000534:rehabilitation*; D000588:Amines / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003463:Cues; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D018757:GABA Modulators / Q000008:administration & dosage / Q000627:therapeutic use; D000077206:Gabapentin; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
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