Alcohol and brain health: from mechanisms to interventions
Article information
J Korean Med Assoc. 2010;53(12):1115-1123
Publication date (electronic) : 2010 December 07
doi :
https://doi.org/10.5124/jkma.2010.53.12.1115
Received 2010 October 13; Accepted 2010 November 01.
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.
Keywords: Alcohol; Neurotoxicity; Neuroprotection
References
1. Sadock BJ, Sadock VA. Kaplan and Sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry 2007. 10th edth ed. Philadelphia: Lippincott Williams & Wilkins;
2. Room R, Babor T, Rehm J. Alcohol and public health. Lancet 2005. 365519–530.
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. 3116–126.
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.
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. 89528–538.
6. Cox WM, Klinger E. A motivational model of alcohol use. J Abnorm Psychol 1988. 97168–180.
7. Moonat S, Starkman BG, Sakharkar A, Pandey SC. Neuroscience of alcoholism: molecular and cellular mechanisms. Cell Mol Life Sci 2010. 6773–88.
8. Harper C, Matsumoto I. Ethanol and brain damage. Curr Opin Pharmacol 2005. 573–78.
9. Clark DB, Thatcher DL, Tapert SF. Alcohol, psychological dysregulation, and adolescent brain development. Alcohol Clin Exp Res 2008. 32375–385.
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.
11. Gonzalez A, Salido GM. Ethanol alters the physiology of neuron-glia communication. Int Rev Neurobiol 2009. 88167–198.
12. Tsai G, Gastfriend DR, Coyle JT. The glutamatergic basis of human alcoholism. Am J Psychiatry 1995. 152332–340.
13. Choi DW. Excitotoxic cell death. J Neurobiol 1992. 231261–1276.
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. 21547–1558.
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. 44128–135.
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. 205529–564.
17. Deitrich RA, Dunwiddie TV, Harris RA, Erwin VG. Mechanism of action of ethanol: initial central nervous system actions. Pharmacol Rev 1989. 41489–537.
18. Haddad JJ. Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects. Biochem Biophys Res Commun 2004. 323361–371.
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. 40163–171.
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. 20361–374.
21. Rivier C. Oxidant anti-oxidant imbalance and effects of ethanol. Front Biosci 1999. 4D514–D519.
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. 29274–280.
23. Lyon I, Kaplowitz N. Acetaldehyde-dependent oxidation of glutathione catalyzed by rat liver cytosol. Biochem Biophys Res Commun 1985. 129949–957.
24. Taylor JM, Crack PJ. Impact of oxidative stress on neuronal survival. Clin Exp Pharmacol Physiol 2004. 31397–406.
25. Wang HJ, Zakhari S, Jung MK. Alcohol, inflammation, and gut-liver-brain interactions in tissue damage and disease development. World J Gastroenterol 2010. 161304–1313.
26. Achur RN, Freeman WM, Vrana KE. Circulating cytokines as biomarkers of alcohol abuse and alcoholism. J Neuroimmune Pharmacol 2010. 583–91.
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. 510.
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. 14365–371.
29. Wu D, Cederbaum AI. Oxidative stress and alcoholic liver disease. Semin Liver Dis 2009. 29141–154.
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. 231901–1908.
31. Quan N, Banks WA. Brain-immune communication pathways. Brain Behav Immun 2007. 21727–735.
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. 281641–1653.
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. 301060–1065.
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. 311833–1838.
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. 20752–757.
36. Geibprasert S, Gallucci M, Krings T. Alcohol-induced changes in the brain as assessed by MRI and CT. Eur Radiol 2010. 201492–1501.
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. 32395–404.
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. 65680–690.
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. 651363–1367.
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. 181511–1514.
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. 25924–934.
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. 1331043–1053.
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. 13036–47.
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. 58974–980.
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. 157737–744.
46. Chen WJ, Maier SE, Parnell SE, West JR. Alcohol and the developing brain: neuroanatomical studies. Alcohol Res Health 2003. 27174–180.
47. Norman AL, Crocker N, Mattson SN, Riley EP. Neuroimaging and fetal alcohol spectrum disorders. Dev Disabil Res Rev 2009. 15209–217.
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. 401012–1020.
49. Chambers RA, Taylor JR, Potenza MN. Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability. Am J Psychiatry 2003. 1601041–1052.
50. White AM, Swartzwelder HS. Hippocampal function during adolescence: a unique target of ethanol effects. Ann N Y Acad Sci 2004. 1021206–220.
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. 322597–2610.
52. Newlin DB, Pretorius MB. Sons of alcoholics report greater hangover symptoms than sons of nonalcoholics: a pilot study. Alcohol Clin Exp Res 1990. 14713–716.
53. Prat G, Adan A, Sánchez-Turet M. Alcohol hangover: a critical review of explanatory factors. Hum Psychopharmacol 2009. 24259–267.
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. 24163–169.
55. Min JA, Lee K, Ki DJ. The application of minerals in managing alcohol hangover: a preliminary review. Curr Drug Abuse Rev 2010. 3110–115.
56. Lee H, Roh S, Kim DJ. Alcohol-induced blackout. Int J Environ Res Public Health 2009. 62783–2792.
57. Goodwin DW. Alcohol amnesia. Addiction 1995. 90315–317.
58. White AM, Best PJ. Effects of ethanol on hippocampal place-cell and interneuron activity. Brain Res 2000. 876154–165.
59. Ogborne AC. Identifying and treating patients with alcohol-related problems. CMAJ 2000. 1621705–1708.
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. 97279–292.
61. Bien TH, Miller WR, Tonigan JS. Brief interventions for alcohol problems: a review. Addiction 1993. 88315–335.
62. Johnson BA. Medication treatment of different types of alcoholism. Am J Psychiatry 2010. 167630–639.
63. Pittler MH, Verster JC, Ernst E. Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials. BMJ 2005. 3311515–1518.
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. 1Geneva: 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. 374109–112.
67. Kornhuber J, Weller M. Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy. Biol Psychiatry 1997. 41135–144.
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. 1052156–162.
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. 11971–983.
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. 30945–48.
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. 105472–476.
72. Luo J. GSK3beta in ethanol neurotoxicity. Mol Neurobiol 2009. 40108–121.
73. Luo J. Lithium-mediated protection against ethanol neurotoxicity. Front Neurosci 2010. 441.
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. 56716–731.
75. Goldman D, Barr CS. Restoring the addicted brain. N Engl J Med 2002. 347843–845.
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. 3411557–1564.
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. 28153–60.
78. Pfefferbaum A. Alcoholism damages the brain, but does moderate alcohol use? Lancet Neurol 2004. 3143–144.
Article information Continued
Copyright © 2010 Korean Medical Association