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Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy

Published online by Cambridge University Press:  03 January 2018

Anne R. Lingford-Hughes ,
P. Acton ,
S. Gacinovic ,
J. Suckling ,
G. F. Busatto ,
S. J. A. Boddington ,
E. Bullmore ,
P. W. Woodruff ,
D. C. Costa  and
L. S. Pilowsky
...Show all authors
Anne R. Lingford-Hughes*
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
P. Acton
Affiliation:
Institute of Nuclear Medicine, UCL Medical School, London
S. Gacinovic
Affiliation:
King's College School of Medicine and Dentistry, London
J. Suckling
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
G. F. Busatto
Affiliation:
Department of Psychology, Institute of Psychiatry, London
S. J. A. Boddington
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
E. Bullmore
Affiliation:
Institute of Nuclear Medicine, UCL Medical School, London
P. W. Woodruff
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
D. C. Costa
Affiliation:
Institute of Nuclear Medicine, UCL Medical School, London
L. S. Pilowsky
Affiliation:
The Maudsley and Institute of Psychiatry
P. J. Ell
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
E. J. Marshall
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
R. W. Kerwin
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, London
*
Dr Anne Lingford-Hughes, Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, SES 8AF, E-mail: sphaarl@iop.bpmf.ac.uk
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Abstract

Background

We tested the hypothesis that reduced levels of the GABA-benzodiazepine receptor occur in alcohol dependency using single photon emission tomography (SPET) and the specific GABA-benzodiazepine ligand, 123l-iomazenil.

Method

Neurologically and cognitively unimpaired abstinent alcohol-dependent (n=12) and non-alcohol-dependent male subjects (n=14) underwent a 123l–iomazenil SPET scan. SPET and magnetic resonance images were co-registered and voxel-based statistical tests performed. Subjects' clinical and alcohol history were obtained with standard questionnaires. The relationships between clinical and alcohol variables and the regional level of GABA-benzodiazepine receptors were investigated using multiple regression analysis.

Results

Abstinent alcohol-dependent subjects had decreased levels of GABA-benzodiazepine receptor compared with non-alcohol-dependent subjects within the frontal, parietal and temporal cortices, including regions in which grey matter atrophy was absent.

Conclusions

Alcohol dependency is associated with reduced GABA-benzodiazepine receptor levels in the absence of grey matter atrophy in some cortical regions, such as within the parietal lobe. Regional variability of reduction in GABA-benzodiazepine receptors demonstrates that alcohol does not have a global, toxic effect on the brain.

Type
Papers
Information
The British Journal of Psychiatry , Volume 173 , Issue 2 , August 1998 , pp. 116 - 122
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

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References

American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washington, DC: APA.Google Scholar
Back, A. T., Ward, C. H., Mendelson, M., et al (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561–571.Google Scholar
Bullmore, E., Brammer, M., Rouleau, G., et al (1995) Computerized brain tissue classification of magnetic resonance images: A new approach to the problem of partial volume artifact. Neurolmage, 2, 133–147.CrossRefGoogle Scholar
Endkott, J. & Spitzer, R. L. (1978) A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia. Archives of General Psychiatry, 35, 837–844.Google Scholar
Fristen, K. J., Holmes, A. P., Worsley, K. J., et al (1995) Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping. 2, 189–210.CrossRefGoogle Scholar
Gllman, S., Koeppe, R. A., Adams, K., et al (1996) Positron emission tomographic studies of cerebral benzodiazepine receptor binding in chronic alcoholics. Annofs of Neurology, 40, 163–171.CrossRefGoogle Scholar
Harper, C. G. & Krll, J. J. (1990) Neuropathology of alcoholism. Alcohol & Alcoholism, 25, 207–216.Google Scholar
Jernlgan, T. L., Butters, N., Di Traglla, G., et al (1991) Reduced cerebral grey matter observed in alcoholics using magnetic resonance imaging. Alcohol Clinical and Experimental Research, 15, 418–427.CrossRefGoogle Scholar
Korpi, E. R., Uusl-Oukari, M., Wegelius, K., et al (1992) Cerebellar and frontal cortical benzodiazepine receptors in human alcoholics and chronically alcohol-drinking rats. Biological Psychiatry, 31, 774–786.CrossRefGoogle ScholarPubMed
Kril, J. J. & Harper, C. G. (1989) Neuronal counts from four cortical regions in alcoholic brains. Acta Neuropathologica. 79, 200–204.Google Scholar
Littleton, J. & Little, H. (1994) Current concepts of ethanol dependence. Addiction, 89, 1397–1412.Google Scholar
Litton, J. E., Neiman, J., Pauli, S., et al (1993) PET analysis of [IIC] flumazenil binding to benzodiazepine receptors in chronic alcohol-dependent men and healthy controls. Psychiatric Research, 50, 1–13.CrossRefGoogle ScholarPubMed
Luddens, H. & Korpi, E. R. (1995) Biological function of GABAa/benzodiazepine receptor heterogeneity. Journal of Psychiatry Research, 29, 77–94.Google Scholar
McGuire, P. K., Bench, C. J., Frith, C. D., et al (1994) Functional anatomy of obsessive-compulsive phenomena. British Journal of Psychiatry, 164, 459–468.Google Scholar
Michael, A. & Mirza, K. A. H. (1995) Serotonin and alcoholism. Journal of Psychiatry Research, 4, 243–256.Google Scholar
Noble, E. P. (1996) Alcoholism and the dopaminergic system: a review. Addiction Biology, 1, 333–348.Google Scholar
Ollat, H., Parvez, H. & Pervez, S. (1988) Review: alcohol and central neurotransmission. Neurochemistry International, 13, 275–300.CrossRefGoogle Scholar
Onishi, Y., Yonekura, Y., Tanaka, F., et al (1996) Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding; the optimal scan time. European Journal of Nuclear Medicine. 23, 1491–1497.CrossRefGoogle ScholarPubMed
Pfefferbaum, A., Sullivan, E. V., Mathalon, D. H., et al (1995) Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clinical and Experimental Research. 19, 1177–1191.Google Scholar
Schuckit, M. A. (1994) Low level of response to alcohol as a predictor of future alcoholism. American Journal of Psychiatry. 151, 184–189.Google Scholar
Silverstein, A. B. (1982) Two- and four-subtests short-form of the Wechsler Adult Intelligence Scale–Revised. Journal of Consulting Clinical Psychology. 50, 415–418.Google Scholar
Simmons, A., Arridge, S. R., Barker, G. J., et al (1996) Simulation of MRI cluster plots and application to neurological segmentation. Magnetic Research Imaging, 14, 73–92.CrossRefGoogle ScholarPubMed
Skinner, H. A. (1982) Development and Validation of a Lifetime Alcohol Consumption Assessment Procedure. Toronto: Addiction Research Foundation.Google Scholar
Spielberger, C. D., Gormen, R. L. & Loche ne, R., et al (1903) Manual for State-Trait Anxiety Inventory. Palo Alto. CA: Consulting Psychologists Press.Google Scholar
Stockwell, T., Murphy, D. & Hodgson, R. (1903) The severity of alcohol dependence questionnaire: its use, reliability and validity. British Journal of Addiction, 78, 145–155.CrossRefGoogle Scholar
Iran, V. T., Snyder, S. H., Major, L. F., et al (1980) GABA receptors are increased in brains of alcoholics. Annals of Neurology, 9, 289–292.Google Scholar
Tsai, G., Gastfriend, D. R. & Coyie, J. Y. (1995) The glutaminergic basis of human alcoholism. American Journal of Psychiatry, 152, 332–340.Google Scholar
Volkow, N. D., Hitzemann, R., Wang, G.-J., et al (1992) Decreased brain metabolism in neurologically intact healthy alcoholics. American Journal of Psychiatry. 151, 178–183.Google Scholar
Volkow, N. D., Wang, G.-J., Hltxemann, R., et al (1993) Decreased cerebral response to inhibitory neurotransmission in alcoholics. American Journal of Psychiatry. 150, 417–422.Google Scholar
Volkow, N. D., Wang, G.-J., Hltxemann, R., et al (1994) Recovery of brain glucose metabolism in detoxified alcoholics. American Journal of Psychiatry. 151, 178–183.Google ScholarPubMed
Volkow, N. D., Wang, G.-J., Begleiter, H., et al (1995) Regional brain metabolic response to lorazepam in subjects at risk for alcoholism. Alcoholism Clinical and Experimental Research, 19, 510–516.Google Scholar
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