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Pharmacopsychiatry 2009; 42: S102-S109
DOI: 10.1055/s-0029-1214396
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Homocysteine, Alcoholism and its Molecular Networks

S. Bleich 1 , T. Hillemacher 1
  • 1Department of Psychiatry, Socialpsychiatry and Psychotherapy, Medical School Hannover, Germany
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Publication History

Publication Date:
11 May 2009 (online)

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Abstract

The emerging research on biomarkers in alcohol dependence has lead to a deeper understanding of the neurobiological mechanisms in alcoholism. The molecular networks and the pathophysiological circuits are complex and not completely unrevealed up to now. One of the most interesting biomarkers described to play an important role in alcohol dependence is the amino-acid homocysteine, which has particularly been linked with brain atrophy and withdrawal seizures. However, the molecular networks of homocysteine are complex and include an important impact on epigenetic regulation via homocysteine's action as a methyl-group donator in human metabolism. So, alterations in human homocysteine levels can influence DNA-methylation of specific gene areas which may change expression and synthesis of proteins possibly important for the genesis and maintenance of alcohol dependence.

References

  • 1 Abdolmaleky HM, Faraone SV, Glatt SJ. et al . Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia.  Schizophr Res. 2004;  67 53-62
    CrossrefPubMedGoogle Scholar
  • 2 Abdolmaleky HM, Smith CL, Faraone SV. et al . Methylomics in psychiatry: Modulation of gene-environment interactions may be through DNA methylation.  Am J Med Genet B Neuropsychiatr Genet. 2004;  127 51-59
    PubMedGoogle Scholar
  • 3 Agartz I, Momenan R, Rawlings RR. et al . Hippocampal volume in patients with alcohol dependence.  Arch Gen Psychiatry. 1999;  56 356-363
    CrossrefPubMedGoogle Scholar
  • 4 Althausen S, Paschen W. Homocysteine-induced changes in mRNA levels of genes coding for cytoplasmic- and endoplasmic reticulum-resident stress proteins in neuronal cell cultures.  Brain Res Mol Brain Res. 2000;  84 32-40
    CrossrefPubMedGoogle Scholar
  • 5 Austin RC, Sood SK, Dorward AM. et al . Homocysteine-dependent alterations in mitochondrial gene expression, function and structure. Homocysteine and H2O2 act synergistically to enhance mitochondrial damage.  J Biol Chem. 1998;  273 30808-30817
    CrossrefPubMedGoogle Scholar
  • 6 Bayerlein K, Hillemacher T, Reulbach U. et al . Alcoholism-associated hyperhomocysteinemia and previous withdrawal seizures.  Biol Psychiatry. 2005;  57 1590-1593
    CrossrefPubMedGoogle Scholar
  • 7 Bisaga A, Popik P. In search of a new pharmacological treatment for drug and alcohol addiction: N-methyl-D-aspartate (NMDA) antagonists.  Drug Alcohol Depend. 2000;  59 1-15
    PubMedGoogle Scholar
  • 8 Bjelland I, Tell GS, Vollset SE. et al . Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study.  Arch Gen Psychiatry. 2003;  60 618-626
    CrossrefPubMedGoogle Scholar
  • 9 Bleich S, Bandelow B, Javaheripour K. et al . Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism.  Neurosci Lett. 2003;  335 179-182
    Google Scholar
  • 10 Bleich S, Bayerlein K, Hillemacher T. et al . An assessment of the potential value of elevated homocysteine in predicting alcohol-withdrawal seizures.  Epilepsia. 2006;  47 934-938
    Google Scholar
  • 11 Bleich S, Bleich K, Kropp S. et al . Moderate alcohol consumption in social drinkers raises plasma homocysteine levels: a contradiction to the ‘French Paradox’?.  Alcohol Alcohol. 2001;  36 189-192
    CrossrefPubMedGoogle Scholar
  • 12 Bleich S, Carl M, Bayerlein K. et al . Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS).  Alcohol Clin Exp Res. 2005;  29 334-336
    CrossrefPubMedGoogle Scholar
  • 13 Bleich S, Degner D, Bandelow B. et al . Plasma homocysteine is a predictor of alcohol withdrawal seizures.  Neuroreport. 2000;  11 2749-2752
    Google Scholar
  • 14 Bleich S, Degner D, Javaheripour K. et al . Homocysteine and alcoholism.  J Neural Transm. 2000;  60 (Suppl) 187-196
    PubMedGoogle Scholar
  • 15 Bleich S, Degner D, Kropp S. et al . Red wine, spirits, beer and serum homocysteine.  Lancet. 2000;  356 512
    PubMedGoogle Scholar
  • 16 Bleich S, Degner D, Sperling W. et al . Homocysteine as a neurotoxin in chronic alcoholism.  Prog Neuropsychopharmacol Biol Psychiatry. 2004;  28 453-464
    CrossrefPubMedGoogle Scholar
  • 17 Bleich S, Degner D, Wiltfang J. et al . Elevated homocysteine levels in alcohol withdrawal.  Alcohol Alcohol. 2000;  35 351-354
    Google Scholar
  • 18 Bleich S, Frieling H, Hillemacher T. Elevated Prenatal Homocysteine Levels and the Risk of Schizophrenia.  Arch Gen Psychiatry. 2007;  64 980-981
    CrossrefPubMedGoogle Scholar
  • 19 Bleich S, Kornhuber J. Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals.  Neurology. 2003;  60 1220 , author reply 1220
    PubMedGoogle Scholar
  • 20 Bleich S, Lenz B, Ziegenbein M. et al . 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
    Google Scholar
  • 21 Bleich S, Lenz B, Ziegenbein M. et al . 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
    Google Scholar
  • 22 Bleich S, Spilker K, Kurth C. et al . Oxidative stress and an altered methionine metabolism in alcoholism.  Neurosci Lett. 2000;  293 171-174
    CrossrefPubMedGoogle Scholar
  • 23 Bleich S, Wilhelm J, Graesel E. et al . Apolipoprotein E epsilon 4 is associated with hippocampal volume reduction in females with alcoholism.  J Neural Transm. 2003;  110 401-411
    CrossrefPubMedGoogle Scholar
  • 24 Bönsch D, Lenz B, Kornhuber J. et al . DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism.  Neuroreport. 2005;  16 167-170
    CrossrefPubMedGoogle Scholar
  • 25 Bönsch D, Lenz B, Reulbach U. et al . Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism.  J Neural Transm. 2004;  111 1611-1616
    CrossrefPubMedGoogle Scholar
  • 26 Bönsch D, Reulbach U, Bayerlein K. et al . Elevated alpha synuclein mRNA levels are associated with craving in patients with alcoholism.  Biol Psychiatry. 2004;  56 984-986
    CrossrefPubMedGoogle Scholar
  • 27 Brown AS, Bottiglieri T, Schaefer CA. et al . Elevated prenatal homocysteine levels as a risk factor for schizophrenia.  Arch Gen Psychiatry. 2007;  64 31-39
    CrossrefPubMedGoogle Scholar
  • 28 Carboni S, Isola R, Gessa GL. et al . Ethanol prevents the glutamate release induced by N-methyl-D-aspartate in the rat striatum.  Neurosci Lett. 1993;  152 133-136
    CrossrefPubMedGoogle Scholar
  • 29 Castro R, Rivera I, Struys EA. et al . Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease.  Clin Chem. 2003;  49 1292-1296
    CrossrefPubMedGoogle Scholar
  • 30 Chan SL, Fu W, Zhang P. et al . Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress.  J Biol Chem. 2004;  279 28733-28743
    CrossrefPubMedGoogle Scholar
  • 31 Chen X, Michaelis ML, Michaelis EK. Effects of chronic ethanol treatment on the expression of calcium transport carriers and NMDA/glutamate receptor proteins in brain synaptic membranes.  J Neurochem. 1997;  69 1559-1569
    PubMedGoogle Scholar
  • 32 Clarke R, Smith AD, Jobst KA. et al . Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease.  Arch Neurol. 1998;  55 1449-1455
    CrossrefPubMedGoogle Scholar
  • 33 Cravo ML, Gloria LM, Selhub J. et al . Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status.  Am J Clin Nutr. 1996;  63 220-224
    PubMedGoogle Scholar
  • 34 D’Emilia DM, Lipton SA. Ratio of S-nitrosohomocyst(e)ine to homocyst(e)ine or other thiols determines neurotoxicity in rat cerebrocortical cultures.  Neurosci Lett. 1999;  265 103-106
    CrossrefPubMedGoogle Scholar
  • 35 Danysz W, Dyr W, Jankowska E. et al . The involvement of NMDA receptors in acute and chronic effects of ethanol.  Alcohol Clin Exp Res. 1992;  16 499-504
    PubMedGoogle Scholar
  • 36 Davidson M, Shanley B, Wilce P. Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study.  Brain Res. 1995;  674 91-96
    CrossrefPubMedGoogle Scholar
  • 37 Detich N, Hamm S, Just G. et al . The methyl donor S-Adenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of S-Adenosylmethionine.  J Biol Chem. 2003;  278 20812-20820
    CrossrefPubMedGoogle Scholar
  • 38 Doerfler W. DNA methylation and gene activity.  Annu Rev Biochem. 1983;  52 93-124
    CrossrefPubMedGoogle Scholar
  • 39 Egger G, Liang G, Aparicio A. et al . Epigenetics in human disease and prospects for epigenetic therapy.  Nature. 2004;  429 457-463
    CrossrefPubMedGoogle Scholar
  • 40 Folbergrova J. Anticonvulsant action of both NMDA and non-NMDA receptor antagonists against seizures induced by homocysteine in immature rats.  Exp Neurol. 1997;  145 442-450
    CrossrefPubMedGoogle Scholar
  • 41 Folbergrova J, Haugvicova R, Mares P. Behavioral and metabolic changes in immature rats during seizures induced by homocysteic acid: the protective effect of NMDA and non-NMDA receptor antagonists.  Exp Neurol. 2000;  161 336-345
    CrossrefPubMedGoogle Scholar
  • 42 Follesa P, Ticku MK. Chronic ethanol-mediated up-regulation of the N-methyl-D-aspartate receptor polypeptide subunits in mouse cortical neurons in culture.  J Biol Chem. 1996;  271 13297-13299
    CrossrefPubMedGoogle Scholar
  • 43 Follesa P, Ticku MK. NMDA receptor upregulation: molecular studies in cultured mouse cortical neurons after chronic antagonist exposure.  J Neurosci. 1996;  16 2172-2178
    PubMedGoogle Scholar
  • 44 Folstein M, Liu T, Peter I. et al . The homocysteine hypothesis of depression.  Am J Psychiatry. 2007;  164 861-867
    CrossrefPubMedGoogle Scholar
  • 45 Frieling H, Bleich S, Otten J. et al . Epigenetic Downregulation of Atrial Natriuretic Peptide but not Vasopressin mRNA Expression in Females with Eating Disorders is Related to Impulsivity.  Neuropsychopharmacology. 2008;  33 2605-2609
    CrossrefPubMedGoogle Scholar
  • 46 Frieling H, Gozner A, Römer KD. et al . Global DNA hypomethylation and DNA hypermethylation of the alpha synuclein promoter in females with anorexia nervosa.  Mol Psychiatry. 2007;  12 229-230
    CrossrefPubMedGoogle Scholar
  • 47 Frosst P, Blom HJ, Milos R. et al . A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.  Nat Genet. 1995;  10 111-113
    CrossrefPubMedGoogle Scholar
  • 48 Fuks F, Hurd PJ, Wolf D. et al . The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation.  J Biol Chem. 2003;  278 4035-4040
    CrossrefPubMedGoogle Scholar
  • 49 Grant KA, Valverius P, Hudspith M. et al . Ethanol withdrawal seizures and the NMDA receptor complex.  Eur J Pharmacol. 1990;  176 289-296
    CrossrefPubMedGoogle Scholar
  • 50 Harper C. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain?.  J Neuropathol Exp Neurol. 1998;  57 101-110
    PubMedGoogle Scholar
  • 51 Hillemacher T, Bayerlein K, Frieling H. et al . Elevated prolactin serum levels and history of alcohol withdrawal seizures.  J Psychiatr Res. 2007;  41 702-706
    CrossrefPubMedGoogle Scholar
  • 52 Hillemacher T, Frieling H, Bayerlein K. et al . Biological markers to predict previous alcohol withdrawal seizures: a risk assessment.  J Neural Transm. 2007;  114 151-154
    CrossrefPubMedGoogle Scholar
  • 53 Hillemacher T, Frieling H, Hartl T. et al . Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving.  J Psychiatr Res. 2009;  43 388-392
    CrossrefPubMedGoogle Scholar
  • 54 Hillemacher T, Frieling H, Luber K. et al . Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal.  Psychoneuroendocrinology. 2008;  , DOI:10.1016/j.psyneuen.2008.1010.1019
    PubMedGoogle Scholar
  • 55 Hillemacher T, Frieling H, Moskau S. et al . Global DNA methylation is influenced by smoking behaviour.  Eur Neuropsychopharmacol. 2008;  18 295-298
    CrossrefPubMedGoogle Scholar
  • 56 Hillemacher T, Reulbach U, Bayerlein K. et al . Plasma homocysteine concentrations do not influence craving in alcohol withdrawal.  Alcohol. 2004;  34 211-215
    CrossrefPubMedGoogle Scholar
  • 57 Hoffman PL, Rabe CS, Grant KA. et al . Ethanol and the NMDA receptor.  Alcohol. 1990;  7 229-231
    CrossrefPubMedGoogle Scholar
  • 58 Holliday R. DNA methylation and epigenetic defects in carcinogenesis.  Mutat Res. 1987;  181 215-217
    PubMedGoogle Scholar
  • 59 Hu XJ, Follesa P, Ticku MK. Chronic ethanol treatment produces a selective upregulation of the NMDA receptor subunit gene expression in mammalian cultured cortical neurons.  Brain Res Mol Brain Res. 1996;  36 211-218
    CrossrefPubMedGoogle Scholar
  • 60 Huang RF, Huang SM, Lin BS. et al . Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells.  Life Sci. 2001;  68 2799-2811
    CrossrefPubMedGoogle Scholar
  • 61 Hultberg B, Berglund M, Andersson A. et al . Elevated plasma homocysteine in alcoholics.  Alcohol Clin Exp Res. 1993;  17 687-689
    CrossrefPubMedGoogle Scholar
  • 62 Ingrosso D, Cimmino A, Perna AF. et al . Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia.  Lancet. 2003;  361 1693-1699
    CrossrefPubMedGoogle Scholar
  • 63 Kenyon SH, Nicolaou A, Gibbons WA. The effect of ethanol and its metabolites upon methionine synthase activity in vitro.  Alcohol. 1998;  15 305-309
    CrossrefPubMedGoogle Scholar
  • 64 Kim WK, Pae YS. Involvement of N-methyl-d-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture.  Neurosci Lett. 1996;  216 117-120
    PubMedGoogle Scholar
  • 65 Kokame K, Agarwala KL, Kato H. et al . Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress.  J Biol Chem. 2000;  275 32846-32853
    CrossrefPubMedGoogle Scholar
  • 66 Koob GF, Mason BJ, De Witte P. et al . Potential neuroprotective effects of acamprosate.  Alcohol Clin Exp Res. 2002;  26 586-592
    CrossrefPubMedGoogle Scholar
  • 67 Kornhuber J, Kaiserauer CH, Kornhuber AW. et al . Alcohol consumption and blood-cerebrospinal fluid barrier dysfunction in man.  Neurosci Lett. 1987;  79 218-222
    CrossrefPubMedGoogle Scholar
  • 68 Kornhuber J, Weller M. Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy.  Biol Psychiatry. 1997;  41 135-144
    PubMedGoogle Scholar
  • 69 Kril JJ, Halliday GM. Brain shrinkage in alcoholics: a decade on and what have we learned?.  Prog Neurobiol. 1999;  58 381-387
    CrossrefPubMedGoogle Scholar
  • 70 Kruman II, Culmsee C, Chan SL. et al . Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity.  J Neurosci. 2000;  20 6920-6926
    PubMedGoogle Scholar
  • 71 Kruman II, Kumaravel TS, Lohani A. et al . Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease.  J Neurosci. 2002;  22 1752-1762
    PubMedGoogle Scholar
  • 72 Kubova H, Folbergrova J, Mares P. Seizures induced by homocysteine in rats during ontogenesis.  Epilepsia. 1995;  36 750-756
    PubMedGoogle Scholar
  • 73 Kurth C, Wegerer V, Degner D. et al . Risk assessment of alcohol withdrawal seizures with a Kohonen feature map.  Neuroreport. 2001;  12 1235-1238
    CrossrefPubMedGoogle Scholar
  • 74 Lenz B, Bleich S, Beutler S. et al . Homocysteine regulates expression of Herp by DNA methylation involving the AARE and CREB binding sites.  Exp Cell Res. 2006;  312 4049-4055
    Google Scholar
  • 75 Liang T, Spence J, Liu L. et al . alpha-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats.  Proc Natl Acad Sci USA. 2003;  100 4690-4695
    CrossrefPubMedGoogle Scholar
  • 76 Liljequist S. The competitive NMDA receptor antagonist, CGP 39551, inhibits ethanol withdrawal seizures.  Eur J Pharmacol. 1991;  192 197-198
    CrossrefPubMedGoogle Scholar
  • 77 Lipton SA, Kim WK, Choi YB. et al . Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.  Proc Natl Acad Sci USA. 1997;  94 5923-5928
    CrossrefPubMedGoogle Scholar
  • 78 Lopez-Serra L, Ballestar E, Fraga MF. et al . A profile of methyl-CpG binding domain protein occupancy of hypermethylated promoter CpG islands of tumor suppressor genes in human cancer.  Cancer Res. 2006;  66 8342-8346
    CrossrefPubMedGoogle Scholar
  • 79 Lovinger DM. Alcohols and neurotransmitter gated ion channels: past, present and future.  Naunyn Schmiedebergs Arch Pharmacol. 1997;  356 267-282
    PubMedGoogle Scholar
  • 80 Lovinger DM. Excitotoxicity and alcohol-related brain damage.  Alcohol Clin Exp Res. 1993;  17 19-27
    CrossrefPubMedGoogle Scholar
  • 81 Maler JM, Seifert W, Huther G. et al . Homocysteine induces cell death of rat astrocytes in vitro.  Neurosci Lett. 2003;  347 85-88
    CrossrefPubMedGoogle Scholar
  • 82 Mash DC, Ouyang Q, Pablo J. et al . Cocaine abusers have an overexpression of alpha-synuclein in dopamine neurons.  J Neurosci. 2003;  23 2564-2571
    PubMedGoogle Scholar
  • 83 Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders.  Trends Neurosci. 2003;  26 137-146
    CrossrefPubMedGoogle Scholar
  • 84 Mayer ML, Westbrook GL. The physiology of excitatory amino acids in the vertebrate central nervous system.  Prog Neurobiol. 1987;  28 197-276
    CrossrefPubMedGoogle Scholar
  • 85 MacKeever MP, Weir DG, Molloy A. et al . Betaine-homocysteine methyltransferase: organ distribution in man, pig and rat and subcellular distribution in the rat.  Clin Sci (Lond). 1991;  81 551-556
    PubMedGoogle Scholar
  • 86 Moghaddam B, Bolinao ML. Biphasic effect of ethanol on extracellular accumulation of glutamate in the hippocampus and the nucleus accumbens.  Neurosci Lett. 1994;  178 99-102
    CrossrefPubMedGoogle Scholar
  • 87 Morrisett RA, Rezvani AH, Overstreet D. et al . MK-801 potently inhibits alcohol withdrawal seizures in rats.  Eur J Pharmacol. 1990;  176 103-105
    CrossrefPubMedGoogle Scholar
  • 88 Nan X, Ng HH, Johnson CA. et al . Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.  Nature. 1998;  393 386-389
    CrossrefPubMedGoogle Scholar
  • 89 Nonaka H, Tsujino T, Watari Y. et al . Taurine prevents the decrease in expression and secretion of extracellular superoxide dismutase induced by homocysteine: amelioration of homocysteine-induced endoplasmic reticulum stress by taurine.  Circulation. 2001;  104 1165-1170
    CrossrefPubMedGoogle Scholar
  • 90 O’Neill J, Cardenas VA, Meyerhoff DJ. Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse.  Alcohol Clin Exp Res. 2001;  25 1673-1682
    CrossrefPubMedGoogle Scholar
  • 91 Outinen PA, Sood SK, Liaw PC. et al . Characterization of the stress-inducing effects of homocysteine.  Biochem J. 1998;  332 ((Pt 1)) 213-221
    PubMedGoogle Scholar
  • 92 Perez RG, Waymire JC, Lin E. et al . A role for alpha-synuclein in the regulation of dopamine biosynthesis.  J Neurosci. 2002;  22 3090-3099
    PubMedGoogle Scholar
  • 93 Pfefferbaum A, Sullivan EV, Mathalon DH. et al . Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics.  Alcohol Clin Exp Res. 1995;  19 1177-1191
    CrossrefPubMedGoogle Scholar
  • 94 Phillips PE, Stuber GD, Heien ML. et al . Subsecond dopamine release promotes cocaine seeking.  Nature. 2003;  422 614-618
    CrossrefPubMedGoogle Scholar
  • 95 Prins ND, Den Heijer T, Hofman A. et al . Homocysteine and cognitive function in the elderly: the Rotterdam Scan Study.  Neurology. 2002;  59 1375-1380
    PubMedGoogle Scholar
  • 96 Rady PL, Szucs S, Grady J. et al . Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations in Texas; a report of a novel MTHFR polymorphic site, G1793A.  Am J Med Genet. 2002;  107 162-168
    CrossrefPubMedGoogle Scholar
  • 97 Rodenhiser D, Mann M. Epigenetics and human disease: translating basic biology into clinical applications.  Cmaj. 2006;  174 341-348
    CrossrefPubMedGoogle Scholar
  • 98 Rozen R. Genetic modulation of homocysteinemia.  Semin Thromb Hemost. 2000;  26 255-261
    Article in Thieme ConnectPubMedGoogle Scholar
  • 99 Sachdev PS, Valenzuela M, Wang XL. et al . Relationship between plasma homocysteine levels and brain atrophy in healthy elderly individuals.  Neurology. 2002;  58 1539-1541
    PubMedGoogle Scholar
  • 100 Selhub J. Homocysteine metabolism.  Annu Rev Nutr. 1999;  19 217-246
    PubMedGoogle Scholar
  • 101 Smith SS, Crocitto L. DNA methylation in eukaryotic chromosome stability revisited: DNA methyltransferase in the management of DNA conformation space.  Mol Carcinog. 1999;  26 1-9
    CrossrefPubMedGoogle Scholar
  • 102 Snell LD, Nunley KR, Lickteig RL. et al . Regional and subunit specific changes in NMDA receptor mRNA and immunoreactivity in mouse brain following chronic ethanol ingestion.  Brain Res Mol Brain Res. 1996;  40 71-78
    CrossrefPubMedGoogle Scholar
  • 103 Stickel F, Choi SW, Kim YI. et al . Effect of chronic alcohol consumption on total plasma homocysteine level in rats.  Alcohol Clin Exp Res. 2000;  24 259-264
    CrossrefPubMedGoogle Scholar
  • 104 Sunden SL, Renduchintala MS, Park EI. et al . Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene.  Arch Biochem Biophys. 1997;  345 171-174
    CrossrefPubMedGoogle Scholar
  • 105 Tsai G, Coyle JT. The role of glutamatergic neurotransmission in the pathophysiology of alcoholism.  Annu Rev Med. 1998;  49 173-184
    CrossrefPubMedGoogle Scholar
  • 106 Tsai GE, Ragan P, Chang R. et al . Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal.  Am J Psychiatry. 1998;  155 726-732
    PubMedGoogle Scholar
  • 107 Ubbink JB, Becker PJ, Vermaak WJ. et al . Results of B-vitamin supplementation study used in a prediction model to define a reference range for plasma homocysteine.  Clin Chem. 1995;  41 1033-1037
    PubMedGoogle Scholar
  • 108 Veldic M, Caruncho HJ, Liu WS. et al . DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains.  Proc Natl Acad Sci USA. 2004;  101 348-353
    PubMedGoogle Scholar
  • 109 Wilhelm J, Bayerlein K, Hillemacher T. et al . Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism.  J Neural Transm. 2006;  113 357-363
    CrossrefPubMedGoogle Scholar
  • 110 Yi P, Melnyk S, Pogribna M. et al . Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation.  J Biol Chem. 2000;  275 29318-29323
    PubMedGoogle Scholar

Correspondence

S. BleichMD 

Department of Psychiatry

Socialpsychiatry and Psychotherapy

Medical School Hannover

Carl-Neuberg-Str. 1

30625 Hannover

Germany

Phone: +49/511/532 65 71

Fax: +49/511/532 24 15

Email: bleich.stefan@mh-hannover.de

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