Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics
- 606 Downloads
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.
This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy.
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.
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.
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.
KeywordsAlcoholism Anticonvulsant Craving Neuroimaging Relapse
This work was conducted under an unrestricted grant from Hythiam, Inc. This funding source had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the paper, or in the decision to submit for publication. Drs. Schacht and Anton are supported by grants from the National Institute on Alcohol Abuse and Alcoholism (T32 AA007474 and K05 AA017435). Portions of this work were presented as a poster at the 34th Annual Meeting of the Research Society on Alcoholism (June 2011, Atlanta, GA, USA).
- American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
- Anton RF, Myrick H, Baros AM, Latham PK, Randall PK, Wright TM, Stewart SH, Waid R, Malcolm R (2009) Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol 29:334–342PubMedCrossRefGoogle Scholar
- First MB, Spitzer RL, Gibbon M, Williams JBW (2002) Structured Clinical Interview for DSM-IV-TR axis I disorders, research version, non-patient edition. Biometrics Research, New York State Psychiatric Institute, New YorkGoogle Scholar
- Grüsser SM, Wrase J, Klein S, Hermann D, Smolka MN, Ruf M, Weber-Fahr W, Flor H, Mann K, Braus DF, Heinz A (2004) Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl) 175:296–302CrossRefGoogle Scholar
- Miller WR (2004) Combined behavioral intervention manual. National Institute on Alcohol Abuse and Alcoholism, BethesdaGoogle Scholar
- O'Daly OG, Trick L, Scaife J, Marshall J, Ball D, Phillips ML, Williams SS, Stephens DN, Duka T (2012) Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism. Neuropsychopharmacology 37:2267–2276PubMedCrossRefGoogle Scholar