J Korean Med Assoc.  2010 Dec;53(12):1115-1123. 10.5124/jkma.2010.53.12.1115.

Alcohol and brain health: from mechanisms to interventions

Affiliations
  • 1Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine, Seoul, Korea. kdj922@chol.com

Abstract

Alcohol-related problems are prevalent and lead to substantial economic, physical, and psychological burden. Among the various effects of alcohol, the effect on the brain is a matter of importance. The brain controls drinking behaviors and may be damaged earlier than other organs by alcohol. Moreover, alcohol-related brain pathologies are difficult to treat once they have progressed. Therefore, we overviewed the mechanisms and results of alcohol-induced brain damage and interventions against it in this article. Alcohol exerts neurotoxic effects mediated by various mechanisms, such as acetaldehyde toxicity, glutamate excitotoxicity, increased oxidative stress, and chronic inflammatory responses. In both functional and structural neuroimaging studies, the evidence of alcohol-induced brain damage was observed in various regions of gray and white matter. Brain damage has been known to be more prominent when it begins during the period of brain development and in women. Symptomatically, alcohol hangovers and alcohol-induced blackouts, which are highly prevalent alcohol-related problems, have been suggested to be early signs of alcohol-related brain damage. However, neurological changes induced by alcohol have been reported to be partly recovered by abstinence. The development of effective interventions would be clinically important. Although following the rules of low-risk drinking and abstinence have been the primary approaches up to the present, studies on mechanism-based neuroprotective interventions, such as acamprosate and memantine, have attempted. Further prospective and well-designed studies of neuroprotective interventions against neurotoxic effects of alcohol are required.

Keyword

Alcohol; Neurotoxicity; Neuroprotection

MeSH Terms

Acetaldehyde
Brain
Drinking
Drinking Behavior
Female
Glutamic Acid
Humans
Memantine
Neuroimaging
Oxidative Stress
Taurine
Acetaldehyde
Glutamic Acid
Memantine
Taurine

Reference

1. Sadock BJ, Sadock VA. Kaplan and Sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry. 2007. 10th ed. Philadelphia: Lippincott Williams & Wilkins.
2. Room R, Babor T, Rehm J. Alcohol and public health. Lancet. 2005. 365:519–530.
Article
3. Verster JC, Stephens R, Penning R, Rohsenow D, McGeary J, Levy D, McKinney A, Finnigan F, Piasecki TM, Adan A, Batty GD, Fliervoet LA, Heffernan T, Howland J, Kim DJ, Kruisselbrink LD, Ling J, McGregor N, Murphy RJ, van Nuland M, Oudelaar M, Parkes A, Prat G, Reed N, Slutske WS, Smith G, Young M. Alcohol Hangover Research Group. The alcohol hangover research group consensus statement on best practice in alcohol hangover research. Curr Drug Abuse Rev. 2010. 3:116–126.
Article
4. Fichter MM, Quadflieg N, Fischer UC. Severity of alcohol-related problems and mortality: results from a 20-year prospective epidemiological community study. Eur Arch Psychiatry Clin Neurosci. 2010. 09. 14. [Epub]. DOI: 10.1007/s00406-010-0141-y.
Article
5. Levenson RW, Sher KJ, Grossman LM, Newman J, Newlin DB. Alcohol and stress response dampening: pharmacological effects, expectancy, and tension reduction. J Abnorm Psychol. 1980. 89:528–538.
Article
6. Cox WM, Klinger E. A motivational model of alcohol use. J Abnorm Psychol. 1988. 97:168–180.
Article
7. Moonat S, Starkman BG, Sakharkar A, Pandey SC. Neuroscience of alcoholism: molecular and cellular mechanisms. Cell Mol Life Sci. 2010. 67:73–88.
Article
8. Harper C, Matsumoto I. Ethanol and brain damage. Curr Opin Pharmacol. 2005. 5:73–78.
Article
9. Clark DB, Thatcher DL, Tapert SF. Alcohol, psychological dysregulation, and adolescent brain development. Alcohol Clin Exp Res. 2008. 32:375–385.
Article
10. Perry JL, Joseph JE, Jiang Y, Zimmerman RS, Kelly TH, Darna M, Huettl P, Dwoskin LP, Bardo MT. Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions. Brain Res Rev. 2010. 09. 15. [Epub]. DOI: 10.1016/j.brainresrev.2010.09.001.
Article
11. Gonzalez A, Salido GM. Ethanol alters the physiology of neuron-glia communication. Int Rev Neurobiol. 2009. 88:167–198.
12. Tsai G, Gastfriend DR, Coyle JT. The glutamatergic basis of human alcoholism. Am J Psychiatry. 1995. 152:332–340.
Article
13. Choi DW. Excitotoxic cell death. J Neurobiol. 1992. 23:1261–1276.
Article
14. Murphy TH, Miyamoto M, Sastre A, Schnaar RL, Coyle JT. Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron. 1989. 2:1547–1558.
Article
15. Ward RJ, Lallemand F, de Witte P. Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse. Alcohol Alcohol. 2009. 44:128–135.
Article
16. Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, Morrow AL. The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress. Psychopharmacology (Berl). 2009. 205:529–564.
Article
17. Deitrich RA, Dunwiddie TV, Harris RA, Erwin VG. Mechanism of action of ethanol: initial central nervous system actions. Pharmacol Rev. 1989. 41:489–537.
18. Haddad JJ. Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects. Biochem Biophys Res Commun. 2004. 323:361–371.
Article
19. Signorini-Allibe N, Gonthier B, Lamarche F, Eysseric H, Barret L. Chronic consumption of ethanol leads to substantial cell damage in cultured rat astrocytes in conditions promoting acetaldehyde accumulation. Alcohol Alcohol. 2005. 40:163–171.
Article
20. Lamarche F, Gonthier B, Signorini N, Eysseric H, Barret L. Impact of ethanol and acetaldehyde on DNA and cell viability of cultured neurones. Cell Biol Toxicol. 2004. 20:361–374.
Article
21. Rivier C. Oxidant anti-oxidant imbalance and effects of ethanol. Front Biosci. 1999. 4:D514–D519.
Article
22. Koop DR. Alcohol metabolism's damaging effects on the cell: a focus on reactive oxygen generation by the enzyme cytochrome P450 2E1. Alcohol Res Health. 2006. 29:274–280.
23. Lyon I, Kaplowitz N. Acetaldehyde-dependent oxidation of glutathione catalyzed by rat liver cytosol. Biochem Biophys Res Commun. 1985. 129:949–957.
Article
24. Taylor JM, Crack PJ. Impact of oxidative stress on neuronal survival. Clin Exp Pharmacol Physiol. 2004. 31:397–406.
Article
25. Wang HJ, Zakhari S, Jung MK. Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development. World J Gastroenterol. 2010. 16:1304–1313.
Article
26. Achur RN, Freeman WM, Vrana KE. Circulating cytokines as biomarkers of alcohol abuse and alcoholism. J Neuroimmune Pharmacol. 2010. 5:83–91.
Article
27. Qin L, He J, Hanes RN, Pluzarev O, Hong JS, Crews FT. Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment. J Neuroinflammation. 2008. 5:10.
Article
28. Valles SL, Blanco AM, Pascual M, Guerri C. Chronic ethanol treatment enhances inflammatory mediators and cell death in the brain and in astrocytes. Brain Pathol. 2004. 14:365–371.
Article
29. Wu D, Cederbaum AI. Oxidative stress and alcoholic liver disease. Semin Liver Dis. 2009. 29:141–154.
Article
30. Wiest R, Moleda L, Zietz B, Hellerbrand C, Schölmerich J, Straub R. Uncoupling of sympathetic nervous system and hypothalamic-pituitary-adrenal axis in cirrhosis. J Gastroenterol Hepatol. 2008. 23:1901–1908.
Article
31. Quan N, Banks WA. Brain-immune communication pathways. Brain Behav Immun. 2007. 21:727–735.
Article
32. Richardson HN, Lee SY, O'Dell LE, Koob GF, Rivier CL. Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state. Eur J Neurosci. 2008. 28:1641–1653.
Article
33. Yoon SJ, Roh S, Lee H, Lee JY, Lee BH, Kim YK, Kim DJ. Possible role of nerve growth factor in the pathogenesis of alcohol dependence. Alcohol Clin Exp Res. 2006. 30:1060–1065.
Article
34. Joe KH, Kim YK, Kim TS, Roh SW, Choi SW, Kim YB, Lee HJ, Kim DJ. Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence. Alcohol Clin Exp Res. 2007. 31:1833–1838.
Article
35. Pfefferbaum A, Lim KO, Desmond JE, Sullivan EV. Thinning of the corpus callosum in older alcoholic men: a magnetic resonance imaging study. Alcohol Clin Exp Res. 1996. 20:752–757.
Article
36. Geibprasert S, Gallucci M, Krings T. Alcohol-induced changes in the brain as assessed by MRI and CT. Eur Radiol. 2010. 20:1492–1501.
Article
37. De Bellis MD, Van Voorhees E, Hooper SR, Gibler N, Nelson L, Hege SG, Payne ME, MacFall J. Diffusion tensor measures of the corpus callosum in adolescents with adolescent onset alcohol use disorders. Alcohol Clin Exp Res. 2008. 32:395–404.
Article
38. Pfefferbaum A, Rosenbloom M, Rohlfing T, Sullivan EV. Degradation of association and projection white matter systems in alcoholism detected with quantitative fiber tracking. Biol Psychiatry. 2009. 65:680–690.
Article
39. Paul CA, Au R, Fredman L, Massaro JM, Seshadri S, Decarli C, Wolf PA. Association of alcohol consumption with brain volume in the Framingham study. Arch Neurol. 2008. 65:1363–1367.
Article
40. Lee E, Jang DP, Kim JJ, An SK, Park S, Kim IY, Kim SI, Yoon KJ, Namkoong K. Alteration of brain metabolites in young alcoholics without structural changes. Neuroreport. 2007. 18:1511–1514.
Article
41. Schweinsburg BC, Taylor MJ, Alhassoon OM, Videen JS, Brown GG, Patterson TL, Berger F, Grant I. Chemical pathology in brain white matter of recently detoxified alcoholics: a 1H magnetic resonance spectroscopy investigation of alcohol-associated frontal lobe injury. Alcohol Clin Exp Res. 2001. 25:924–934.
Article
42. Gazdzinski S, Durazzo TC, Mon A, Yeh PH, Meyerhoff DJ. Cerebral white matter recovery in abstinent alcoholics: a multimodality magnetic resonance study. Brain. 2010. 133:1043–1053.
Article
43. Bartsch AJ, Homola G, Biller A, Smith SM, Weijers HG, Wiesbeck GA, Jenkinson M, De Stefano N, Solymosi L, Bendszus M. Manifestations of early brain recovery associated with abstinence from alcoholism. Brain. 2007. 130:36–47.
Article
44. Ende G, Welzel H, Walter S, Weber-Fahr W, Diehl A, Hermann D, Heinz A, Mann K. Monitoring the effects of chronic alcohol consumption and abstinence on brain metabolism: a longitudinal proton magnetic resonance spectroscopy study. Biol Psychiatry. 2005. 58:974–980.
Article
45. De Bellis MD, Clark DB, Beers SR, Soloff PH, Boring AM, Hall J, Kersh A, Keshavan MS. Hippocampal volume in adolescent-onset alcohol use disorders. Am J Psychiatry. 2000. 157:737–744.
Article
46. Chen WJ, Maier SE, Parnell SE, West JR. Alcohol and the developing brain: neuroanatomical studies. Alcohol Res Health. 2003. 27:174–180.
47. Norman AL, Crocker N, Mattson SN, Riley EP. Neuroimaging and fetal alcohol spectrum disorders. Dev Disabil Res Rev. 2009. 15:209–217.
Article
48. Durston S, Hulshoff Pol HE, Casey BJ, Giedd JN, Buitelaar JK, van Engeland H. Anatomical MRI of the developing human brain: what have we learned? J Am Acad Child Adolesc Psychiatry. 2001. 40:1012–1020.
Article
49. Chambers RA, Taylor JR, Potenza MN. Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry. 2003. 160:1041–1052.
Article
50. White AM, Swartzwelder HS. Hippocampal function during adolescence: a unique target of ethanol effects. Ann N Y Acad Sci. 2004. 1021:206–220.
Article
51. Read JP, Merrill JE, Kahler CW, Strong DR. Predicting functional outcomes among college drinkers: reliability and predictive validity of the Young Adult Alcohol Consequences Questionnaire. Addict Behav. 2007. 32:2597–2610.
Article
52. Newlin DB, Pretorius MB. Sons of alcoholics report greater hangover symptoms than sons of nonalcoholics: a pilot study. Alcohol Clin Exp Res. 1990. 14:713–716.
Article
53. Prat G, Adan A, Sánchez-Turet M. Alcohol hangover: a critical review of explanatory factors. Hum Psychopharmacol. 2009. 24:259–267.
Article
54. Piasecki TM, Slutske WS, Wood PK, Hunt-Carter EE. Frequency and correlates of diary-measured hangoverlike experiences in a college sample. Psychol Addict Behav. 2010. 24:163–169.
Article
55. Min JA, Lee K, Ki DJ. The application of minerals in managing alcohol hangover: a preliminary review. Curr Drug Abuse Rev. 2010. 3:110–115.
Article
56. Lee H, Roh S, Kim DJ. Alcohol-induced blackout. Int J Environ Res Public Health. 2009. 6:2783–2792.
Article
57. Goodwin DW. Alcohol amnesia. Addiction. 1995. 90:315–317.
Article
58. White AM, Best PJ. Effects of ethanol on hippocampal place-cell and interneuron activity. Brain Res. 2000. 876:154–165.
Article
59. Ogborne AC. Identifying and treating patients with alcohol-related problems. CMAJ. 2000. 162:1705–1708.
60. Moyer A, Finney JW, Swearingen CE, Vergun P. Brief interventions for alcohol problems: a meta-analytic review of controlled investigations in treatment-seeking and non-treatment-seeking populations. Addiction. 2002. 97:279–292.
Article
61. Bien TH, Miller WR, Tonigan JS. Brief interventions for alcohol problems: a review. Addiction. 1993. 88:315–335.
Article
62. Johnson BA. Medication treatment of different types of alcoholism. Am J Psychiatry. 2010. 167:630–639.
Article
63. Pittler MH, Verster JC, Ernst E. Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials. BMJ. 2005. 331:1515–1518.
Article
64. World Health Organization. International guide for monitoring alcohol consumption and related harm. 2000. Geneva: World Health Organization.
65. Ezzati M, Lopez AD, Rodgers A, Murray CJ. Comparative quantification of health risks: global and regional burden of disease attributable to selected major risk factors. 2004. Vol. 1. Geneva: World Health Organization.
66. Adde-Michel C, Hennebert O, Laudenbach V, Marret S, Leroux P. Effect of acamprosate on neonatal excitotoxic cortical lesions in in utero alcohol-exposed hamsters. Neurosci Lett. 2005. 374:109–112.
Article
67. Kornhuber J, Weller M. Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy. Biol Psychiatry. 1997. 41:135–144.
Article
68. Maler JM, Esselmann H, Wiltfang J, Kunz N, Lewczuk P, Reulbach U, Bleich S, Ruther E, Kornhuber J. Memantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons. Brain Res. 2005. 1052:156–162.
Article
69. Cheon Y, Park J, Joe KH, Kim DJ. The effect of 12-week open-label memantine treatment on cognitive function improvement in patients with alcohol-related dementia. Int J Neuropsychopharmacol. 2008. 11:971–983.
Article
70. Lukoyanov NV, Paula-Barbosa MM. Memantine, but not dizocilpine, ameliorates cognitive deficits in adult rats withdrawn from chronic ingestion of alcohol. Neurosci Lett. 2001. 309:45–48.
Article
71. Isaac WL, McDaniel WF, Corley JD, Emard S, McDonald C, Young LK, Ray C. D-cycloserine and early ethanol exposure in developing rats. Psychol Rep. 2009. 105:472–476.
Article
72. Luo J. GSK3beta in ethanol neurotoxicity. Mol Neurobiol. 2009. 40:108–121.
73. Luo J. Lithium-mediated protection against ethanol neurotoxicity. Front Neurosci. 2010. 4:41.
Article
74. Bonthius DJ, Luong T, Bonthius NE, Hostager BS, Karacay B. Nitric oxide utilizes NF-kappaB to signal its neuroprotective effect against alcohol toxicity. Neuropharmacology. 2009. 56:716–731.
Article
75. Goldman D, Barr CS. Restoring the addicted brain. N Engl J Med. 2002. 347:843–845.
Article
76. Berger K, Ajani UA, Kase CS, Gaziano JM, Buring JE, Glynn RJ, Hennekens CH. Light-to-moderate alcohol consumption and risk of stroke among U.S. male physicians. N Engl J Med. 1999. 341:1557–1564.
Article
77. Sacco RL, Elkind M, Boden-Albala B, Lin IF, Kargman DE, Hauser WA, Shea S, Paik MC. The protective effect of moderate alcohol consumption on ischemic stroke. JAMA. 1999. 281:53–60.
Article
78. Pfefferbaum A. Alcoholism damages the brain, but does moderate alcohol use? Lancet Neurol. 2004. 3:143–144.
Article
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