Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking

doi:10.1016/j.biopsych.2005.06.009

Biological Psychiatry

Volume 59, Issue 1, 1 January 2006, Pages 85-93

https://doi.org/10.1016/j.biopsych.2005.06.009 Get rights and content

Background

Gamma-aminobutyric acid (GABA)ergic adaptations contribute to the neurobiology of ethanol dependence and withdrawal. Clinical data suggest that tobacco smoking attenuates alcohol withdrawal symptoms. This study’s objective was to measure time-dependent cortical GABA levels with sobriety in ethanol-dependent patients with mild to moderate withdrawal severity, controlling for alcoholism-related neurotoxicity and smoking.

Methods

Proton magnetic resonance spectroscopy (MRS) was used to measure occipital cortical N-acetylaspartate (NAA), glutamate plus glutamine, and GABA in 12 ethanol-dependent men at approximately 1 week and 1 month of medication-free sobriety on an inpatient unit. Eight healthy men were studied once. The tissue composition of the MRS volume was determined.

Results

Adjusting for less white matter in patients, GABA differed insignificantly between ethanol-dependent patients (smokers plus nonsmokers) and healthy subjects. In early sobriety, nonsmoking patients had more GABA than did smoking patients, but by 1 month, GABA decreased in nonsmokers without changing in smokers. Smoking was associated with increased glutamate plus glutamine in patients and healthy subjects, adjusting for NAA levels.

Conclusions

These data do not show that deficits in cortical GABA contribute directly to acute ethanol withdrawal. If smoking prevents withdrawal-related changes in cortical GABA systems, it may contribute to comorbidity of alcoholism and tobacco smoking.

Section snippets

Ethanol-Dependent Patients

Sixteen medically healthy men meeting DSM-IV criteria for ethanol dependence (age 39.0 ± 8.2 years), without other lifetime psychiatric diagnoses or substance abuse diagnoses within the past year besides nicotine dependence on the basis of a structured diagnostic interview (First et al 1996) and without psychiatric diagnoses in their first-degree relatives as indicated by the family history method (Nurnberger et al 1994), completed a detailed evaluation. Individuals with a maternal history of

Greater Cortical GM Volume in Smokers

No significant reductions in percent GM were observed in ethanol-dependent patients, and there was no significant interaction between alcoholism and smoking effects. No facets of alcoholism history or alcohol withdrawal were related to tissue composition or any metabolite in patients, and smoking status was unrelated to tissue composition in patients and in comparison subjects. However, smoking [F(1,17.45) = 3.99, p = .04) was associated with more GM in smokers (least squares [LS] mean = 50.24

Discussion

The results of this study of patients whose mild to moderate symptoms of withdrawal allowed them to undergo withdrawal without medications suggest the following: 1) ethanol-dependent patients had reduced voxel WM; 2) adjusting for WM deficits, there were no abnormalities in GABA levels in patients relative to healthy subjects; 3) nonsmoking ethanol-dependent patients initially had more GABA than smoking patients; and 4) nonsmoking patients, but not smoking patients, showed an abstinence-related

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Original articleCortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking

Background

Methods

Results

Conclusions

Section snippets

Ethanol-Dependent Patients

Greater Cortical GM Volume in Smokers

Discussion

Psychiatry Res

Life Sci

Biol Psychiatry

Int Rev Neurobiol

Drug Alcohol Depend

Neurosci Biobehav Rev

Magn Reson Imaging

Magn Reson Imaging

Neurochem Int

J Neurol Sci

Neurol Clin

Eur J Pharmacol

Eur Neuropsychopharmacol

Eur Neuropsychopharmacol

J Subst Abuse

Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil

Am J Psychiatry

Changes in cigarette smoking and coffee drinking after alcohol detoxification in alcoholics

Addiction

Relationship between alcohol and tobacco dependencies among alcoholics who smoke

Addiction

Measurement of GABA following GABA-transaminase inhibition by gabaculineA 1H and 31P NMR spectroscopic study of rat brain in vivo

Magn Reson Med

Characterization of macromolecule resonances in the 1H NMR spectrum of rat brain

Magn Reson Med

Preliminary evidence of low cortical GABA levels in localized 1H-MR spectra of alcohol-dependent and hepatic encephalopathy patients

Am J Psychiatry

Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholismCorrelation with clinical and neuropsychological data

AJNR: Am J Neuroradiol

Molecular genetic analysis of the role of GABAergic systems in the behavioral and cellular actions of alcohol

Behav Genet

Clinical correlates of cigarette smoking and nicotine dependence in alcohol-dependent men and womenThe Collaborative Study Group on the Genetics of Alcoholism

Alcohol Alcohol

Disproportionate atrophy of cerebral white matter in chronic alcoholics

Arch Neurol

Cigarette smoking exacerbates chronic alcohol-induced brain damage. A preliminary metabolite imaging study

Alcohol Clin Exp Res

Structured Clinical Interview for the DSM-IV Axis I Disorders-Patient Edition (SCID-I/P, Version 2.0)

Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder

Am J Psychiatry

The role of GABA(A) receptors in the acute and chronic effects of ethanol

Psychopharmacol Bull

Smoking and drinking among alcoholics in treatmentCross-sectional and longitudinal relationships

J Stud Alcohol

The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain?

J Neuropathol Exp Neurol

An introduction to alcohol-induced brain damage and its causes

Alcohol Alcohol

Adaptation of gamma-aminobutyric acid type A receptors to alcohol exposureStudies with stably transfected cells

J Pharmacol Exp Ther

The Fagerström Test for Nicotine DependenceA revision of the Fagerström Tolerance Questionnaire

Br J Addict

Glutamate receptors in alcohol withdrawal-induced neurotoxicity

Metab Brain Dis

Tetrodotoxin-sensitive enhancement of inhibition in CA1 pyramidal neurones by nicotine

Neuroreport

Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging

Alcohol Clin Exp Res

Original article
Cortical Gamma-Aminobutyric Acid Levels and the Recovery from Ethanol Dependence: Preliminary Evidence of Modification by Cigarette Smoking

Preliminary evidence of low cortical GABA levels in localized ¹H-MR spectra of alcohol-dependent and hepatic encephalopathy patients