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Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics

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Abstract

Rationale

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.

Objectives

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, 29425, USA

    Joseph P. Schacht, Raymond F. Anton, Patrick K. Randall, Xingbao Li, Scott Henderson & Hugh Myrick

  2. Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA

    Hugh Myrick

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  1. Joseph P. Schacht
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  2. Raymond F. Anton
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  3. Patrick K. Randall
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  4. Xingbao Li
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  5. Scott Henderson
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  6. Hugh Myrick
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Correspondence to Joseph P. Schacht.

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Schacht, J.P., Anton, R.F., Randall, P.K. et al. Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics. Psychopharmacology 227, 627–637 (2013). https://doi.org/10.1007/s00213-013-2996-x

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  • DOI: https://doi.org/10.1007/s00213-013-2996-x

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