Genetics and epigenetics of alcohol dependence

Agrawal A, Lynskey MT: Are there genetic influences on addiction: evidence from family, adoption and twin studies. Addiction 2008, 103: 1069–1081. 10.1111/j.1360-0443.2008.02213.x Enoch MA, Goldman D: The genetics of alcoholism and alcohol abuse. Curr Psychiatr Rep 2001, 3: 144–151. 10.1007/s11920-001-0012-3 Goldman D, Oroszi G, Ducci F: The genetics of addictions: uncovering the genes. Nat Rev Genet 2005, 6: 521–532. Lynskey MT, Agrawal A, Heath AC: Genetically informative research on adolescent substance use: methods, findings, and challenges. J Am Acad Child Adolesc Psychiatr 2010, 49: 1202–1214. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM: Finding the missing heritability of complex diseases. Nature 2009, 461: 747–753. 10.1038/nature08494 Razin A, Riggs AD: DNA methylation and gene function. Science 1980, 210: 604–610. 10.1126/science.6254144 Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A: Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009, 324: 930–935. 10.1126/science.1170116 Kriaucionis S, Heintz N: The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 2009, 324: 929–930. 10.1126/science.1169786 Jin SG, Wu X, Li AX, Pfeifer GP: Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res 2011, 39: 5015–5024. 10.1093/nar/gkr120 Jaenisch R, Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 2003,33(Suppl):245–254. Jones PA: Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012, 13: 484–492. 10.1038/nrg3230 Ramchandani S, Bhattacharya SK, Cervoni N, Szyf M: DNA methylation is a reversible biological signal. Proc Natl Acad Sci USA 1999, 96: 6107–6112. 10.1073/pnas.96.11.6107 Lillycrop KA, Burdge GC: Epigenetic mechanisms linking early nutrition to long term health. Best Pract Res Clin Endocrinol Metab 2012, 26: 667–676. 10.1016/j.beem.2012.03.009 Bollati V, Baccarelli A: Environmental epigenetics. Heredity (Edinb) 2010, 105: 105–112. 10.1038/hdy.2010.2 Robison AJ, Nestler EJ: Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci 2012, 12: 623–637. 10.1038/nri3265 Szyf M, McGowan P, Meaney MJ: The social environment and the epigenome. Environ Mol Mutagen 2008, 49: 46–60. 10.1002/em.20357 Muller DJ, Likhodi O, Heinz A: Neural markers of genetic vulnerability to drug addiction. Curr Top Behav Neurosci 2010, 3: 277–299. 10.1007/7854_2009_25 Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S, Hinrichs AL, Almasy L, Breslau N, Culverhouse RC, Dick DM, Edenberg HJ, Foroud T, Grucza RA, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Krueger RF, Kuperman S, Lynskey M, Mann K, Neuman RJ, Nothen MM, Nurnberger JI Jr, Porjesz B, Ridinger M, Saccone NL, Saccone SF, Schuckit MA, Tischfield JA, Wang JC, Rietschel M, Goate AM, Rice JP: A genome-wide association study of alcohol dependence. Proc Natl Acad Sci USA 2010, 107: 5082–5087. 10.1073/pnas.0911109107 Edenberg HJ, Koller DL, Xuei X, Wetherill L, McClintick JN, Almasy L, Bierut LJ, Bucholz KK, Goate A, Aliev F, Dick D, Hesselbrock V, Hinrichs A, Kramer J, Kuperman S, Nurnberger JI Jr, Rice JP, Schuckit MA, Taylor R, Todd Webb B, Tischfield JA, Porjesz B, Foroud T: Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcohol Clin Exp Res 2010, 34: 840–852. 10.1111/j.1530-0277.2010.01156.x Frank J, Cichon S, Treutlein J, Ridinger M, Mattheisen M, Hoffmann P, Herms S, Wodarz N, Soyka M, Zill P, Maier W, Mossner R, Gaebel W, Dahmen N, Scherbaum N, Schmal C, Steffens M, Lucae S, Ising M, Muller-Myhsok B, Nothen MM, Mann K, Kiefer F, Rietschel M: Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster. Addict Biol 2012, 17: 171–180. 10.1111/j.1369-1600.2011.00395.x Heath AC, Whitfield JB, Martin NG, Pergadia ML, Goate AM, Lind PA, McEvoy BP, Schrage AJ, Grant JD, Chou YL, Zhu R, Henders AK, Medland SE, Gordon SD, Nelson EC, Agrawal A, Nyholt DR, Bucholz KK, Madden PA, Montgomery GW: A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications. Biol Psychiatr 2011, 70: 513–518. 10.1016/j.biopsych.2011.02.028 Johnson C, Drgon T, Liu QR, Walther D, Edenberg H, Rice J, Foroud T, Uhl GR: Pooled association genome scanning for alcohol dependence using 104,268 SNPs: validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism. Am J Med Genet B Neuropsychiatr Genet 2006, 141B: 844–853. 10.1002/ajmg.b.30346 Kendler KS, Kalsi G, Holmans PA, Sanders AR, Aggen SH, Dick DM, Aliev F, Shi J, Levinson DF, Gejman PV: Genomewide association analysis of symptoms of alcohol dependence in the molecular genetics of schizophrenia (MGS2) control sample. Alcohol Clin Exp Res 2011, 35: 963–975. 10.1111/j.1530-0277.2010.01427.x Lind PA, Macgregor S, Vink JM, Pergadia ML, Hansell NK, de Moor MH, Smit AB, Hottenga JJ, Richter MM, Heath AC, Martin NG, Willemsen G, de Geus EJ, Vogelzangs N, Penninx BW, Whitfield JB, Montgomery GW, Boomsma DI, Madden PA: A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations. Twin Res Hum Genet 2010, 13: 10–29. 10.1375/twin.13.1.10 Treutlein J, Cichon S, Ridinger M, Wodarz N, Soyka M, Zill P, Maier W, Moessner R, Gaebel W, Dahmen N, Fehr C, Scherbaum N, Steffens M, Ludwig KU, Frank J, Wichmann HE, Schreiber S, Dragano N, Sommer WH, Leonardi-Essmann F, Lourdusamy A, Gebicke-Haerter P, Wienker TF, Sullivan PF, Nothen MM, Kiefer F, Spanagel R, Mann K, Rietschel M: Genome-wide association study of alcohol dependence. Arch Gen Psychiatr 2009, 66: 773–784. 10.1001/archgenpsychiatry.2009.83 Wang KS, Liu X, Zhang Q, Pan Y, Aragam N, Zeng M: A meta-analysis of two genome-wide association studies identifies 3 new loci for alcohol dependence. J Psychiatr Res 2011, 45: 1419–1425. 10.1016/j.jpsychires.2011.06.005 Zuo L, Gelernter J, Zhang CK, Zhao H, Lu L, Kranzler HR, Malison RT, Li CS, Wang F, Zhang XY, Deng HW, Krystal JH, Zhang F, Luo X: Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q. Neuropsychopharmacology 2012, 37: 557–566. 10.1038/npp.2011.229 Zuo L, Zhang CK, Wang F, Li CS, Zhao H, Lu L, Zhang XY, Zhang H, Zhang F, Krystal JH, Luo X: A novel, functional and replicable risk gene region for alcohol dependence identified by genome-wide association study. PLoS One 2011, 6: e26726. 10.1371/journal.pone.0026726 Wang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, Harari O, Koller DL, Wetherill L, Agrawal A, Almasy L, Brooks AI, Bucholz K, Dick D, Hesselbrock V, Johnson EO, Kang S, Kapoor M, Kramer J, Kuperman S, Madden PA, Manz N, Martin NG, McClintick JN, Montgomery GW, Nurnberger JI Jr, Rangaswamy M, Rice J, Schuckit M, Tischfield JA, Whitfield JB, Xuei X, Porjesz B, Heath AC, Edenberg HJ, Bierut LJ, Goate AM: A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol Psychiatr 2012. Epub ahead of print Yan J, Aliev F, Webb BT, Kendler KS, Williamson VS, Edenberg HJ, Agrawal A, Kos MZ, Almasy L, Nurnberger JI Jr, Schuckit MA, Kramer JR, Rice JP, Kuperman S, Goate AM, Tischfield JA, Porjesz B, Dick DM: Using genetic information from candidate gene and genome-wide association studies in risk prediction for alcohol dependence. Addict Biol 2013. Epub ahead of print. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P, International Schizophrenia C: Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009, 460: 748–752. Covault J, Tennen H, Armeli S, Conner TS, Herman AI, Cillessen AH, Kranzler HR: Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use. Biol Psychiatr 2007, 61: 609–616. 10.1016/j.biopsych.2006.05.018 Kaufman J, Yang BZ, Douglas-Palumberi H, Crouse-Artus M, Lipschitz D, Krystal JH, Gelernter J: Genetic and environmental predictors of early alcohol use. Biol Psychiatr 2007, 61: 1228–1234. 10.1016/j.biopsych.2006.06.039 Laucht M, Treutlein J, Schmid B, Blomeyer D, Becker K, Buchmann AF, Schmidt MH, Esser G, Jennen-Steinmetz C, Rietschel M, Zimmermann US, Banaschewski T: Impact of psychosocial adversity on alcohol intake in young adults: moderation by the LL genotype of the serotonin transporter polymorphism. Biol Psychiatr 2009, 66: 102–109. 10.1016/j.biopsych.2009.02.010 Nilsson KW, Sjoberg RL, Damberg M, Alm PO, Ohrvik J, Leppert J, Lindstrom L, Oreland L: Role of the serotonin transporter gene and family function in adolescent alcohol consumption. Alcohol Clin Exp Res 2005, 29: 564–570. 10.1097/01.ALC.0000159112.98941.B0 Bau CH, Almeida S, Hutz MH: The TaqI A1 allele of the dopamine D2 receptor gene and alcoholism in Brazil: association and interaction with stress and harm avoidance on severity prediction. Am J Med Genet 2000, 96: 302–306. 10.1002/1096-8628(20000612)96:3<302::AID-AJMG13>3.0.CO;2-I Madrid GA, MacMurray J, Lee JW, Anderson BA, Comings DE: Stress as a mediating factor in the association between the DRD2 TaqI polymorphism and alcoholism. Alcohol 2001, 23: 117–122. 10.1016/S0741-8329(00)00138-5 van der Zwaluw CS, Engels RC, Vermulst AA, Franke B, Buitelaar J, Verkes RJ, Scholte RH: Interaction between dopamine D2 receptor genotype and parental rule-setting in adolescent alcohol use: evidence for a gene-parenting interaction. Mol Psychiatr 2010, 15: 727–735. 10.1038/mp.2009.4 Laucht M, Blomeyer D, Buchmann AF, Treutlein J, Schmidt MH, Esser G, Jennen-Steinmetz C, Rietschel M, Zimmermann US, Banaschewski T: Catechol-O-methyltransferase Val158 Met genotype, parenting practices and adolescent alcohol use: testing the differential susceptibility hypothesis. J Child Psychol Psychiatr 2012, 53: 351–359. 10.1111/j.1469-7610.2011.02408.x Schellekens AF, Franke B, Ellenbroek B, Cools A, de Jong CA, Buitelaar JK, Verkes RJ: COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence. Addict Biol 2013, 18: 344–356. 10.1111/j.1369-1600.2012.00438.x Nilsson KW, Sjoberg RL, Wargelius HL, Leppert J, Lindstrom L, Oreland L: The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumption. Addiction 2007, 102: 389–398. 10.1111/j.1360-0443.2006.01702.x Nilsson KW, Wargelius HL, Sjoberg RL, Leppert J, Oreland L: The MAO-A gene, platelet MAO-B activity and psychosocial environment in adolescent female alcohol-related problem behaviour. Drug Alcohol Depend 2008, 93: 51–62. 10.1016/j.drugalcdep.2007.08.022 Nilsson KW, Comasco E, Aslund C, Nordquist N, Leppert J, Oreland L: MAOA genotype, family relations and sexual abuse in relation to adolescent alcohol consumption. Addict Biol 2011, 16: 347–355. 10.1111/j.1369-1600.2010.00238.x Dick DM, Agrawal A, Schuckit MA, Bierut L, Hinrichs A, Fox L, Mullaney J, Cloninger CR, Hesselbrock V, Nurnberger JI Jr, Almasy L, Foroud T, Porjesz B, Edenberg H, Begleiter H: Marital status, alcohol dependence, and GABRA2: evidence for gene-environment correlation and interaction. J Stud Alcohol 2006, 67: 185–194. Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M: Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatr 2008, 63: 146–151. 10.1016/j.biopsych.2007.04.026 Nelson EC, Agrawal A, Pergadia ML, Wang JC, Whitfield JB, Saccone FS, Kern J, Grant JD, Schrage AJ, Rice JP, Montgomery GW, Heath AC, Goate AM, Martin NG, Madden PA: H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence. Addict Biol 2010, 15: 1–11. 10.1111/j.1369-1600.2009.00181.x Schmid B, Blomeyer D, Treutlein J, Zimmermann US, Buchmann AF, Schmidt MH, Esser G, Rietschel M, Banaschewski T, Schumann G, Laucht M: Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds. Int J Neuropsychopharmacol 2010, 13: 703–714. 10.1017/S1461145709990290 Ray LA, Sehl M, Bujarski S, Hutchison K, Blaine S, Enoch MA: The Crhr1 Gene, Trauma Exposure, And Alcoholism Risk: A Test Of G x E Effects. Genes Brain Behav 2013. Epub ahead of print. Robison AJ, Nestler EJ: Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci 2011, 12: 623–637. Bleich S, Degner D, Javaheripour K, Kurth C, Kornhuber J: Homocysteine and alcoholism. J Neural Transm Suppl 2000, 60: 187–196. Bleich S, Degner D, Wiltfang J, Maler JM, Niedmann P, Cohrs S, Mangholz A, Porzig J, Sprung R, Ruther E, Kornhuber J: Elevated homocysteine levels in alcohol withdrawal. Alcohol Alcohol 2000, 35: 351–354. 10.1093/alcalc/35.4.351 Cravo ML, Gloria LM, Selhub J, Nadeau MR, Camilo ME, Resende MP, Cardoso JN, Leitao CN, Mira FC: Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am J Clin Nutr 1996, 63: 220–224. Hultberg B, Berglund M, Andersson A, Frank A: Elevated plasma homocysteine in alcoholics. Alcohol Clin Exp Res 1993, 17: 687–689. 10.1111/j.1530-0277.1993.tb00820.x Heese P, Linnebank M, Semmler A, Muschler MA, Heberlein A, Frieling H, Stoffel-Wagner B, Kornhuber J, Banger M, Bleich S, Hillemacher T: Alterations of homocysteine serum levels during alcohol withdrawal are influenced by folate and riboflavin: results from the German Investigation on Neurobiology in Alcoholism (GINA). Alcohol Alcohol 2012, 47: 497–500. 10.1093/alcalc/ags058 Bleich S, Hillemacher T: Homocysteine, Alcoholism and its Molecular Networks. Pharmacopsychiatry 2009, 42: S102-S109. 10.1055/s-0029-1214396 Shukla SD, Velazquez J, French SW, Lu SC, Ticku MK, Zakhari S: Emerging role of epigenetics in the actions of alcohol. Alcohol Clin Exp Res 2008, 32: 1525–1534. 10.1111/j.1530-0277.2008.00729.x Bonsch D, Lenz B, Reulbach U, Kornhuber J, Bleich S: Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm 2004, 111: 1611–1616. 10.1007/s00702-004-0232-x Bonsch D, Lenz B, Fiszer R, Frieling H, Kornhuber J, Bleich S: Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm 2006, 113: 1299–1304. 10.1007/s00702-005-0413-2 Ingrosso D, Perna AF: Epigenetics in hyperhomocysteinemic states. A special focus on uremia. Biochim Biophys Acta 2009, 1790: 892–899. 10.1016/j.bbagen.2008.11.010 Castro R, Rivera I, Struys EA, Jansen EE, Ravasco P, Camilo ME, Blom HJ, Jakobs C, Tavares de Almeida I: Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease. Clin Chem 2003, 49: 1292–1296. 10.1373/49.8.1292 Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ: Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000, 275: 29318–29323. 10.1074/jbc.M002725200 Ingrosso D, Cimmino A, Perna AF, Masella L, De Santo NG, De Bonis ML, Vacca M, D'Esposito M, D'Urso M, Galletti P, Zappia V: Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 2003, 361: 1693–1699. 10.1016/S0140-6736(03)13372-7 Bonsch D, Hothorn T, Krieglstein C, Koch M, Nehmer C, Lenz B, Reulbach U, Kornhuber J, Bleich S: Daily variations of homocysteine concentration may influence methylation of DNA in normal healthy individuals. Chronobiol Int 2007, 24: 315–326. 10.1080/07420520701290565 Zhang H, Herman AI, Kranzler HR, Anton RF, Simen AA, Gelernter J: Hypermethylation of OPRM1 promoter region in European Americans with alcohol dependence. J Hum Genet 2012, 57: 670–675. 10.1038/jhg.2012.98 Biermann T, Reulbach U, Lenz B, Frieling H, Muschler M, Hillemacher T, Kornhuber J, Bleich S: N-methyl-D-aspartate 2b receptor subtype (NR2B) promoter methylation in patients during alcohol withdrawal. J Neural Transm 2009, 116: 615–622. 10.1007/s00702-009-0212-2 Bleich S, Lenz B, Ziegenbein M, Beutler S, Frieling H, Kornhuber J, Bonsch D: Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol Clin Exp Res 2006, 30: 587–591. 10.1111/j.1530-0277.2006.00068.x Bonsch D, Lenz B, Kornhuber J, Bleich S: DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism. Neuroreport 2005, 16: 167–170. 10.1097/00001756-200502080-00020 Heberlein A, Muschler M, Frieling H, Behr M, Eberlein C, Wilhelm J, Groschl M, Kornhuber J, Bleich S, Hillemacher T: Epigenetic down regulation of nerve growth factor during alcohol withdrawal. Addict Biol 2011, 18: 508–510. Nieratschker V, Grosshans M, Frank J, Strohmaier J, von der Goltz C, El-Maarri O, Witt SH, Cichon S, Nothen MM, Kiefer F, Rietschel M: Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age. Addict Biol 2012. Epub ahead of print. Hillemacher T, Frieling H, Hartl T, Wilhelm J, Kornhuber J, Bleich S: Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving. J Psychiatr Res 2009, 43: 388–392. 10.1016/j.jpsychires.2008.04.006 Hillemacher T, Frieling H, Luber K, Yazici A, Muschler MA, Lenz B, Wilhelm J, Kornhuber J, Bleich S: Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal. Psychoneuroendocrinology 2009, 34: 555–560. 10.1016/j.psyneuen.2008.10.019 Philibert RA, Gunter TD, Beach SR, Brody GH, Madan A: MAOA methylation is associated with nicotine and alcohol dependence in women. Am J Med Genet B Neuropsychiatr Genet 2008, 147B: 565–570. 10.1002/ajmg.b.30778 Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A: The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B Neuropsychiatr Genet 2008, 147B: 543–549. 10.1002/ajmg.b.30657 Muschler MA, Hillemacher T, Kraus C, Kornhuber J, Bleich S, Frieling H: DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. J Neural Transm 2010, 117: 513–519. 10.1007/s00702-010-0378-7 Taqi MM, Bazov I, Watanabe H, Sheedy D, Harper C, Alkass K, Druid H, Wentzel P, Nyberg F, Yakovleva T, Bakalkin G: Prodynorphin CpG-SNPs associated with alcohol dependence: elevated methylation in the brain of human alcoholics. Addict Biol 2011, 16: 499–509. 10.1111/j.1369-1600.2011.00323.x Zhang H, Herman AI, Kranzler HR, Anton RF, Zhao H, Zheng W, Gelernter J: Array-based profiling of DNA methylation changes associated with alcohol dependence. Alcohol Clin Exp Res 2013,37(Suppl 1):E108-E115. Philibert RA, Plume JM, Gibbons FX, Brody GH, Beach SR: The impact of recent alcohol use on genome wide DNA methylation signatures. Front Genet 2012, 3: 54. Zhang R, Miao Q, Wang C, Zhao R, Li W, Haile CN, Hao W, Zhang XY: Genome-wide DNA methylation analysis in alcohol dependence. Addict Biol 2013, 18: 392–403. 10.1111/adb.12037 Wedekind D, Neumann K, Falkai P, Malchow B, Engel KR, Jamrozinski K, Havemann-Reinecke U: S100B and homocysteine in the acute alcohol withdrawal syndrome. Eur Arch Psychiatr Clin Neurosci 2011, 261: 133–138. 10.1007/s00406-010-0121-2