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Chronic Alcohol Consumption, Abstinence and Relapse: Brain Proton Magnetic Resonance Spectroscopy Studies in Animals and Humans

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Behavioral Neurobiology of Alcohol Addiction

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 13))

Abstract

This chapter summarizes the peer-reviewed literature of proton magnetic resonance spectroscopy (1H MRS) studies on the effects of chronic and excessive alcohol consumption in both the animal and human brain. After a brief summary of the neuropathology of alcohol use disorders (AUD), we describe the primary brain metabolites measured by in vivo 1H MRS. We then focus on published MRS studies of animal models of alcohol dependence and of treatment-seeking humans with AUD. We also summarize the scant MRS research on the much larger fraction of treatment-naïve individuals with AUD and the similarities and discrepancies relative to treatment-seekers. It is exceedingly apparent that premorbid and/or comorbid disorders/conditions, especially chronic smoking, among individuals with AUD contribute to the considerable variability in the pattern and magnitude of neurobiological and neurocognitive abnormalities in AUD. Therefore, we also review studies on the neurobiological consequences of the combined effects of chronic drinking and smoking in AUD. Finally, as AUD is characterized by a chronically relapsing/remitting course over lifetime and identification of those at greatest risk for relapse is important, we review 1H MRS studies on brain spectroscopic measures that contribute to the prediction of relapse in AUD. We conclude with an overall assessment of the MRS research literature on brain alcohol effects, the role of animal and human studies in understanding the disease, and discuss the need of widely integrative MRS studies of cohorts that include individuals with comorbidies that are reflective of the general population with AUD.

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Abbreviations

AUD:

Alcohol use disorders

CNS:

Central nervous system.

Cho:

Choline-containing compounds

Cr:

Creatine and phosphocreatine

CSF:

Cerebrospinal fluid

GABA:

Gamma aminobutyric acid,

Glu:

Glutamate

GM:

Gray matter

NAA:

N-acetylaspartate

NAAG:

N-acetylaspartylglutamate

mI:

Myoinositol

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

WM:

White matter

1H MRS:

Proton magnetic resonance spectroscopy.

1H MRSI:

Proton magnetic resonance spectroscopic imaging

References

  • Adinoff B, Kramer GL, Petty F (1995) Levels of gamma-aminobutyric acid in cerebrospinal fluid and plasma during alcohol withdrawal. Psychiatry Res 59:137–144

    CAS  PubMed  Google Scholar 

  • Babikian T, Freier MC, Ashwal S, Riggs ML, Burley T, Holshouser BA (2006) MR spectroscopy: predicting long-term neuropsychological outcome following pediatric TBI. J Magn Reson Imaging 24:801–811

    PubMed  Google Scholar 

  • Bartsch AJ, Homola G, Biller A, Smith SM, Weijers HG, Wiesbeck GA, Jenkinson M, De Stefano N, Solymosi L, Bendszus M (2007) Manifestations of early brain recovery associated with abstinence from alcoholism. Brain 130:36–47

    PubMed  Google Scholar 

  • Baslow MH (2003) N-acetylaspartate in the vertebrate brain: metabolism and function. Neurochem Res 28:941–953

    CAS  PubMed  Google Scholar 

  • Baslow MH, Guilfoyle DN (2007) Using proton magnetic resonance imaging and spectroscopy to understand brain “activation”. Brain Lang 102:153–164

    PubMed  Google Scholar 

  • Behar K et al (1999) Preliminary evidenceof low cortical GABA levels in localized 1H-MR spectra of alcohol-dependent and hepatic encephalopathy patients. Am J Psychiatry 156:952–954

    CAS  PubMed  Google Scholar 

  • Benarroch EE (2008) N-acetylaspartate and N-acetylaspartylglutamate: neurobiology and clinical significance. Neurology 70:1353–1357

    PubMed  Google Scholar 

  • Bendszus M, Weijers HG, Wiesbeck G, Warmuth-Metz M, Bartsch AJ, Engels S, Boning J, Solymosi L (2001) Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data. Am J Neuroradiol 22:1926–1932

    CAS  PubMed  Google Scholar 

  • Bertolino A, Sciota D, Brudaglio F, Altamura M, Blasi G, Bellomo A, Antonucci N, Callicott JH, Goldberg TE, Scarabino T, Weinberger DR, Nardini M (2003) Working memory deficits and levels of N-acetylaspartate in patients with schizophreniform disorder. Am J Psychiatry 160:483–489

    PubMed  Google Scholar 

  • Bleich S, Degner D, Sperling W, Bonsch D, Thurauf N, Kornhuber J (2004) Homocysteine as a neurotoxin in chronic alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 28:453–464

    CAS  PubMed  Google Scholar 

  • Bolo N, Nedelec JF, Muzet M, De Witte P, Dahchour A, Durbin P, Macher JP (1998) Central effects of acamprosate: part 2. Acamprosate modifies the brain in vivo proton magnetic resonance spectrum in healthy young male volunteers. Psychiatry Res 82:115–127

    CAS  PubMed  Google Scholar 

  • Boulanger Y, Labelle M, Khiat A (2000) Role of phospholipase A(2) on the variations of the choline signal intensity observed by 1H magnetic resonance spectroscopy in brain diseases. Brain Res Brain Res Rev 33:380–389

    CAS  PubMed  Google Scholar 

  • Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15:289–298

    CAS  PubMed  Google Scholar 

  • Braunova Z, Kasparova S, Mlynarik V, Mierisova S, Liptaj T, Tkac I, Gvozdjakova A (2000) Metabolic changes in rat brain after prolonged ethanol consumption measured by 1H and 31P MRS experiments. Cell Mol Neurobiol 20:703–715

    CAS  PubMed  Google Scholar 

  • Brenner RE, Munro PM, Williams SC, Bell JD, Barker GJ, Hawkins CP, Landon DN, McDonald WI (1993) The proton NMR spectrum in acute EAE: the significance of the change in the Cho:Cr ratio. Magn Reson Med 29:737–745

    CAS  PubMed  Google Scholar 

  • Choi C, Bhardwaj PP, Kalra S, Casault CA, Yasmin US, Allen PS, Coupland NJ (2007) Measurement of GABA and contaminants in gray and white matter in human brain in vivo. Magn Reson Med 58:27–33

    CAS  PubMed  Google Scholar 

  • Coffman JA, Petty F (1985) Plasma GABA levels in chronic alcoholics. Am J Psychiatry 142:1204–1205

    CAS  PubMed  Google Scholar 

  • Crews FT, Nixon K (2009) Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol 44:115–127

    CAS  PubMed  Google Scholar 

  • Crews FT, Collins MA, Dlugos C, Littleton J, Wilkins L, Neafsey EJ, Pentney R, Snell LD, Tabakoff B, Zou J, Noronha A (2004) Alcohol-induced neurodegeneration: when, where and why? Alcohol Clin Exp Res 28:350–364

    PubMed  Google Scholar 

  • Daeppen JB, Smith TL, Danko GP, Gordon L, Landi NA, Nurnberger JI Jr, Bucholz KK, Raimo E, Schuckit MA (2000) Clinical correlates of cigarette smoking and nicotine dependence in alcohol-dependent men and women. The collaborative study group on the genetics of alcoholism. Alcohol Alcohol 35:171–175

    CAS  PubMed  Google Scholar 

  • Dahchour A, Lallemand F, Ward RJ, De Witte P (2005) Production of reactive oxygen species following acute ethanol or acetaldehyde and its reduction by acamprosate in chronically alcoholized rats. Eur J Pharmacol 520:51–58

    CAS  PubMed  Google Scholar 

  • Dawson DA, Goldstein RB, Grant BF (2007) Rates and correlates of relapse among individuals in remission from DSM-IV alcohol dependence: a 3 year follow-up. Alcohol Clin Exp Res 31:2036–2045

    PubMed  Google Scholar 

  • De Stefano N, Matthews PM, Arnold DL (1995) Reversible decreases in N-acetylaspartate after acute brain injury. Magn Reson Med 34:721–727

    PubMed  Google Scholar 

  • De Witte P (2004) Imbalance between neuroexcitatory and neuroinhibitory amino acids causes craving for ethanol. Addict Behav 29:1325–1339

    PubMed  Google Scholar 

  • Dlugos CA, Pentney RJ (1997) Morphometric evidence that the total number of synapses on Purkinje neurons of old F344 rats is reduced after long-term ethanol treatment and restored to control levels after recovery. Alcohol and Alcoholism 32:161–172

    CAS  PubMed  Google Scholar 

  • Durazzo TC, Meyerhoff DJ (2007) Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism. Front Biosci 12:4079–4100

    CAS  PubMed  Google Scholar 

  • Durazzo TC, Gazdzinski S, Banys P, Meyerhoff DJ (2004) Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study. Alcohol Clin Exp Res 28:1849–1860

    CAS  PubMed  Google Scholar 

  • Durazzo TC, Gazdzinski S, Banys P, Meyerhoff DJ (2006a) Brain metabolite concentrations and neurocognition during short-term recovery from alcohol dependence: Preliminary evidence of the effects of concurrent chronic cigarette smoking. Alc Clin Exp Research 30:539–551

    CAS  Google Scholar 

  • Durazzo TC, Rothlind JC, Gazdzinski S, Banys P, Meyerhoff DJ (2006b) A comparison of neurocognitive function in nonsmoking and chronically smoking short-term abstinent alcoholics. Alcohol 39:1–11

    PubMed  Google Scholar 

  • Durazzo TC, Gazdzinski S, Meyerhoff DJ (2007) The neurobiological and neurocognitive consequences of chronic cigarette smoking in alcohol use disorders. Alcohol Alcohol 42:174–185

    CAS  PubMed  Google Scholar 

  • Durazzo TC, Gazdzinski S, Yeh PH, Meyerhoff DJ (2008) Combined neuroimaging, neurocognitive and psychiatric factors to predict alcohol consumption following treatment for alcohol dependence. Alcohol Alcoholi 43:683–691

    Google Scholar 

  • Durazzo T, Gazdzinski S, Mon A, Meyerhoff D (2010a) Cortical perfusion in alcohol-dependent individuals during short-term abstinence: relationships to resumption of hazardous drinking after treatment. Alcohol 44:201–210

    PubMed Central  PubMed  Google Scholar 

  • Durazzo TC, Pathak V, Gazdzinski S, Mon A, Meyerhoff DJ (2010b) Metabolite levels in the brain reward pathway discriminate those who remain abstinent from those who resume hazardous alcohol consumption after treatment for alcohol dependence. J Stud Alcohol Drugs 71:278–289

    PubMed  Google Scholar 

  • Ende G, Braus DF, Walter S, Weber-Fahr W, Soher B, Maudsley AA, Henn FA (2000) Effects of age, medication, and illness duration on the N-acetyl aspartate signal of the anterior cingulate region in schizophrenia. Schizophr Res 41:389–395

    CAS  PubMed  Google Scholar 

  • Ende G, Welzel H, Walter S, Weber-Fahr W, Diehl A, Hermann D, Heinz A, Mann K (2005) Monitoring the Effects of Chronic Alcohol Consumption and Abstinence on Brain Metabolism: A Longitudinal Proton Magnetic Resonance Spectroscopy Study. Biol Psychiatry 58:974–980

    CAS  PubMed  Google Scholar 

  • Ende G, Walter S, Welzel H, Demirakca T, Wokrina T, Ruf M, Ulrich M, Diehl A, Henn FA, Mann K (2006) Alcohol consumption significantly influences the MR signal of frontal choline-containing compounds. Neuroimage 32:740–746

    PubMed  Google Scholar 

  • Ende G, Hermann D, Hoerst M, Tunc-Skarka N, Oberthuer G, Wichert S, Rabinstein J, Weber-Fahr W, Mann K, Vollstaedt-Kein S (2010) Frontal white matter choline-containing compounds increase with alcohol consumption and glutamate decreases with increasing addiction criteria. ISMRM, Stockholm, Sweden, pp Prog #: 2160

    Google Scholar 

  • Epperson CN, O’Malley S, Czarkowski KA, Gueorguieva R, Jatlow P, Sanacora G, Rothman DL, Krystal JH, Mason GF (2005) Sex, GABA, and nicotine: the impact of smoking on cortical GABA levels across the menstrual cycle as measured with proton magnetic resonance spectroscopy. Biol Psychiatry 57:44–48

    CAS  PubMed  Google Scholar 

  • Fabricius K, Pakkenberg H, Pakkenberg B (2007) No changes in neocortical cell volumes or glial cell numbers in chronic alcoholic subjects compared to control subjects. Alcohol Alcohol 42:400–406

    PubMed  Google Scholar 

  • Fein G, Landman B (2005) Treated and treatment-naïve alcoholics come from different populations. Alcohol 35:19–26

    PubMed  Google Scholar 

  • Fein G, Meyerhoff DJ, Di Sclafani V, Ezekiel F, Poole N, MacKay S, Dillon WP, Constans J-M, Weiner MW (1994) 1H magnetic resonance spectroscopic imaging separates neuronal from Glial changes in alcohol-related brain atrophy. Chapter in NIAAA Research Monograph No. 27/Alcohol and Glial Cells: 227–241

    Google Scholar 

  • Fein G, Di Sclafani V, Cardenas VA, Goldmann H, Tolou-Shams M, Meyerhoff DJ (2002) Cortical gray matter loss in treatment–naïve alcohol dependent individuals. Alcohol Clin Exp Res 26:558–564

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ferguson KJ, MacLullich AM, Marshall I, Deary IJ, Starr JM, Seckl JR, Wardlaw JM (2002) Magnetic resonance spectroscopy and cognitive function in healthy elderly men. Brain 125:2743–2749

    PubMed  Google Scholar 

  • Fisher SK, Novak JE, Agranoff BW (2002) Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance. J Neurochem. 82:736–754

    CAS  PubMed  Google Scholar 

  • Friend KB, Malloy PF, Sindelar HA (2005) The effects of chronic nicotine and alcohol use on neurocognitive function. Addict Behav 30:193–202

    PubMed  Google Scholar 

  • Frishknecht U, Hermann D, Hoerst N, Tunc-Skarka N, Kiefer F, Ende G, Mann KF (2010) Increased ACC glutamate levels in patients during alcohol withdrawal return to normal after two weeks of abstinence. Alcohol Clin Exp Res 34(suppl.):132A

    Google Scholar 

  • Gallinat J, Kunz D, Lang UE, Neu P, Kassim N, Kienast T, Seifert F, Schubert F, Bajbouj M (2007a) Association between cerebral glutamate and human behaviour: the sensation seeking personality trait. Neuroimage 34:671–678

    CAS  PubMed  Google Scholar 

  • Gallinat J, Lang UE, Jacobsen LK, Bajbouj M, Kalus P, von Haebler D, Seifert F, Schubert F (2007b) Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic resonance spectroscopy at 3 T. J Clin Psychopharmacol 27:80–84

    CAS  PubMed  Google Scholar 

  • Gazdzinski S, Durazzo TC, Studholme C, Song E, Banys P, Meyerhoff DJ (2005) Quantitative brain MRI in alcohol dependence: preliminary evidence for effects of concurrent chronic cigarette smoking on regional brain volumes. Alcohol Clin Exp Res 29:1484–1495

    CAS  PubMed  Google Scholar 

  • Gazdzinski S, Durazzo T, Jahng GH, Ezekiel F, Banys P, Meyerhoff D (2006) Effects of chronic alcohol dependence and chronic cigarette smoking on cerebral perfusion: a preliminary magnetic resonance study. Alcohol Clin Exp Res 30:947–958

    PubMed Central  PubMed  Google Scholar 

  • Gazdzinski S, Durazzo TC, Weiner MW, Meyerhoff DJ (2008a) Are treated alcoholics representative of the entire population with alcohol use disorders? A magnetic resonance study of brain injury. Alcohol 42:67–76

    PubMed Central  PubMed  Google Scholar 

  • Gazdzinski S, Durazzo TC, Yeh PH, Hardin D, Banys P, Meyerhoff DJ (2008b) Chronic cigarette smoking modulates injury and short-term recovery of the medial temporal lobe in alcoholics. Psychiatry Res 162:133–145

    CAS  PubMed Central  PubMed  Google Scholar 

  • Glass JM, Adams KM, Nigg JT, Wong MM, Puttler LI, Buu A, Jester JM, Fitzgerald HE, Zucker RA (2006) Smoking is associated with neurocognitive deficits in alcoholism. Drug Alcohol Depend 82:119–126

    PubMed Central  PubMed  Google Scholar 

  • Hansson AC, Nixon K, Rimondini R, Damadzic R, Sommer WH, Eskay R, Crews FT, Heilig M (2010) Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats. Int J Neuropsychopharmacol 13:583–593

    CAS  PubMed  Google Scholar 

  • Harding AJ, Wong A, Svoboda M, Kril JJ, Halliday GM (1997) Chronic alcohol consumption does not cause hippocampal neuron loss in humans. Hippocampus 7:78–87

    CAS  PubMed  Google Scholar 

  • Harper C (1998) The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? Journal of Neuropathology and Experimental Neurology 57:101–110

    CAS  PubMed  Google Scholar 

  • Harper C (2009) The neuropathology of alcohol-related brain damage. Alcohol Alcohol 44:136–140

    CAS  PubMed  Google Scholar 

  • Harper C, Kril J (1989) Patterns of neuronal loss in the cerebral cortex in chronic alcoholic patients. J.Neurol.Sci. 92:81–89

    CAS  PubMed  Google Scholar 

  • Harper C, Dixon G, Sheedy D, Garrick T (2003) Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre. Progress in Neuro-Psychopharmacology and Biological Psychiatry 27:951–961

    CAS  PubMed  Google Scholar 

  • Harris BR, Gibson DA, Prendergast MA, Blanchard JA, Holley RC, Hart SR, Scotland RL, Foster TC, Pedigo NW, Littleton JM (2003) The neurotoxicity induced by ethanol withdrawal in mature organotypic hippocampal slices might involve cross-talk between metabotropic glutamate type 5 receptors and N-methyl-D-aspartate receptors. Alcohol Clin Exp Res 27:1724–1735

    CAS  PubMed  Google Scholar 

  • Hasin DS, Stinson FS, Ogburn E, Grant BF (2007) Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 64:830–842

    PubMed  Google Scholar 

  • Hazell AS, Butterworth RF (1999) Hepatic encephalopathy: An update of pathophysiologic mechanisms. Proc Soc Exp Biol Med 222:99–112

    CAS  PubMed  Google Scholar 

  • He J, Overstreet DH, Crews FT (2009) Abstinence from moderate alcohol self-administration alters progenitor cell proliferation and differentiation in multiple brain regions of male and female P rats. Alcohol Clin Exp Res 33:129–138

    CAS  PubMed  Google Scholar 

  • Hetherington HP, Newcomer BR, Pan JW (1998) Measurements of human cerebral GABA at 4.1 T using numerically optimized editing pulses. Magn Reson Med 39:6–10

    CAS  PubMed  Google Scholar 

  • Hirakawa K, Uekusa K, Sato S, Nihira M (1994) MRI and MRS studies on acute effects of ethanol in the rat brain. Japanese Journal of Legal Medicine 48:63–74

    CAS  PubMed  Google Scholar 

  • Hoerst M, Weber-Fahr W, Tunc-Skarka N, Ruf M, Bohus M, Schmahl C, Ende G (2010) Glutamate levels in the anterior cingulate cortex correlate with self-reported impulsivity in patients with borderline personality disorder and healthy controls. Arch Gen Psychiatry In Press

    Google Scholar 

  • Hugg JW, Kuzniecky RI, Gilliam FG, Morawetz RB, Faught RE, Hetherington HP (1996) Normalization of contralateral metabolic function following temporal lobectomy demonstrated by h-1 magnetic resonance spectroscopic imaging. Ann.Neurol. V40:236–239

    Google Scholar 

  • Jagannathan NR, Desai NG, Raghunathan P (1996) Brain metabolite changes in alcoholism: An in vivo proton magnetic resonance spectroscopy (MRS) study. Magnetic Resonance Imaging 14:553–557

    CAS  PubMed  Google Scholar 

  • Jansen JF, Backes WH, Nicolay K, Kooi ME (2006) 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology 240:318–332

    PubMed  Google Scholar 

  • Jensen GB, Pakkenberg B (1993) Do alcoholics drink their neurons away? Lancet 342:1201–1204

    CAS  PubMed  Google Scholar 

  • John U, Meyer C, Rumpf HJ, Schumann A, Thyrian JR, Hapke U (2003) Strength of the relationship between tobacco smoking, nicotine dependence and the severity of alcohol dependence syndrome criteria in a population-based sample. Alcohol Alcohol 38:606–612

    PubMed  Google Scholar 

  • Kalivas PW, O’Brien C (2008) Drug addiction as a pathology of staged neuroplasticity. Neuropsychopharmacology 33:166–180

    CAS  PubMed  Google Scholar 

  • Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162:1403–1413

    PubMed  Google Scholar 

  • Kalivas PW, Lalumiere RT, Knackstedt L, Shen H (2009) Glutamate transmission in addiction. Neuropharmacology 56(Suppl 1):169–173

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ke Y, Cohen BM, Lowen S, Hirashima F, Nassar L, Renshaw PF (2002) Biexponential transverse relaxation (T(2)) of the proton MRS creatine resonance in human brain. Magn Reson Med 47:232–238

    CAS  PubMed  Google Scholar 

  • Korbo L (1999) Glial cell loss in the hippocampus of alcoholics. Alcohol Clin Exp Res 23:164–168

    CAS  PubMed  Google Scholar 

  • Kril JJ, Halliday GM (1999) Brain shrinkage in alcoholics: a decade on and what have we learned? Prog Neurobiol 58:381–387

    CAS  PubMed  Google Scholar 

  • Kril JJ, Harding AJ, Wong A, Svoboda MD, Halliday GM (1996) Is the hippocampus damaged in alcoholics with memory loss? Alcohol: Clin Exp Res 20:76A

    Google Scholar 

  • Lee H, Holburn GH, Price RR (2003a) Proton MR spectroscopic studies of chronic alcohol exposure on the rat brain. J Magn Reson Imaging 18:147–151

    PubMed  Google Scholar 

  • Lee PL, Yiannoutsos CT, Ernst T, Chang L, Marra CM, Jarvik JG, Richards TL, Kwok EW, Kolson DL, Simpson D, Tang CY, Schifitto G, Ketonen LM, Meyerhoff DJ, Lenkinski RE, Gonzalez RG, Navia BA (2003b) A multi-center 1H MRS study of the AIDS dementia complex: Validation and preliminary analysis. J Magn Reson Imaging 17:625–633

    PubMed  Google Scholar 

  • Li BS, Babb JS, Soher BJ, Maudsley AA, Gonen O (2002) Reproducibility of 3D proton spectroscopy in the human brain. Magn Reson Med 47:439–446

    CAS  PubMed  Google Scholar 

  • Littleton J (1995) Acamprosate in alcohol dependence: how does it work? Addiction 90:1179–1188

    CAS  PubMed  Google Scholar 

  • Maisto SA, Connors GJ (2006) Relapse in the addictive behaviors: integration and future directions. Clin Psychol Rev 26:229–231

    PubMed  Google Scholar 

  • Mann K, Batra A, Gunthner A, Schroth G (1992) Do women develop alcoholic brain damage more readily than men? Alcohol Clin Exp Res, pp 1052–1056

    Google Scholar 

  • Mansell D, Penk W, Hankin CS, Lee A, Spiro A 3rd, Skinner KM, Hsieh J, Kazis LE (2006) The illness burden of alcohol-related disorders among VA patients: the veterans health study. J Ambul Care Manage 29:61–70

    PubMed  Google Scholar 

  • Martin PR, Gibbs SJ, Nimmerrichter AA, Riddle WR, Welch LW, Willcott MR (1995) Brain proton magnetic resonance spectroscopy studies in recently abstinent alcoholics. Alcohol Clin Exp Res 19:1078–1082

    CAS  PubMed  Google Scholar 

  • Martinez-Bisbal MC, Arana E, Marti-Bonmati L, Martinez-Granados B, Celda B (2006) Cognitive impairment: classification by proton magnetic resonance spectroscopy and the contributions of conventional magnetic resonance imaging]. Radiologia 48:301–307

    CAS  PubMed  Google Scholar 

  • Mason GF, Petrakis IL, de Graaf RA, Gueorguieva R, Guidone E, Coric V, Epperson CN, Rothman DL, Krystal JH (2006) Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence: preliminary evidence of modification by cigarette smoking. Biol Psychiatry 59:85–93

    CAS  PubMed  Google Scholar 

  • Maudsley AA, Domenig C, Govind V, Darkazanli A, Studholme C, Arheart K, Bloomer C (2009) Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI). Magn Reson Med 61:548–559

    CAS  PubMed Central  PubMed  Google Scholar 

  • McFarland K, Lapish CC, Kalivas PW (2003) Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 23:3531–3537

    CAS  PubMed  Google Scholar 

  • Mertens JR, Lu YW, Parthasarathy S, Moore C, Weisner CM (2003) Medical and psychiatric conditions of alcohol and drug treatment patients in an HMO: comparison with matched controls. Arch Intern Med 163:2511–2517

    PubMed  Google Scholar 

  • Meyerhoff DJ, Durazzo TC (2008) Proton magnetic resonance spectroscopy in alcohol use disorders: a potential new endophenotype? Alcohol Clin Exp Res 32:1146–1158

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meyerhoff D, Blumenfeld R, Truran D, Lindgren J, Flenniken D, Cardenas V, Chao LL, Rothlind J, Studholme C, Weiner H (2004) Effects of heavy drinking, binge drinking, and family history of alcoholism on regional brain metabolites. Alcohol Clin Exp Res 28:650–661

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miguel-Hidalgo JJ, Wei J, Andrew M, Overholser JC, Jurjus G, Stockmeier CA, Rajkowska G (2002) Glia pathology in the prefrontal cortex in alcohol dependence with and without depressive symptoms. Biol Psychiatry 52:1121–1133

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miguel-Hidalgo JJ, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G (2006) Reduced glial and neuronal packing density in the orbitofrontal cortex in alcohol dependence and its relationship with suicide and duration of alcohol dependence. Alcohol Clin Exp Res 30:1845–1855

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller BL, Chang L, Booth R, Ernst T, Cornford M, Nikas D, McBride D, Jenden DJ (1996) In vivo 1H MRS choline: correlation with in vitro chemistry/histology. Life Sciences 58:1929–1935

    CAS  PubMed  Google Scholar 

  • Modi S, Bhattacharya M, Kumar P, Deshpande SN, Tripathi RP, Khushu S (2009) Brain metabolite changes in alcoholism: Localized proton magnetic resonance spectroscopy study of the occipital lobe. Eur J Radiol

    Google Scholar 

  • Moffett JR, Namboodiri MA, Cangro CB, Neale JH (1991) Immunohistochemical localization of N-acetylaspartate in rat brain. Neuroreport 2:131–134

    CAS  PubMed  Google Scholar 

  • Mon A, Durazzo TC, Gazdzinski S, Meyerhoff DJ (2009) The Impact of Chronic Cigarette Smoking on Recovery From Cortical Gray Matter Perfusion Deficits in Alcohol Dependence: Longitudinal Arterial Spin Labeling MRI. Alcohol Clin Exp Res

    Google Scholar 

  • Mon A, Durazzo TC, Meyerhoff DJ (2010) Metabolite levels by magnetic resonance spectroscopy during abstinence from alcohol. Alcohol Clin Exp Res 34(supplement):81A

    Google Scholar 

  • Moss HB, Chen CM, Yi HY (2007) Subtypes of alcohol dependence in a nationally representative sample. Drug Alcohol Depend 91:149–158

    PubMed Central  PubMed  Google Scholar 

  • Nicholas PC, Kim D, Crews FT, Macdonald JM (2008) 1H NMR-based metabolomic analysis of liver, serum, and brain following ethanol administration in rats. Chem Res Toxicol 21:408–420

    CAS  PubMed  Google Scholar 

  • Ohrmann P, Kugel H, Bauer J, Siegmund A, Kolkebeck K, Suslow T, Wiedl KH, Rothermundt M, Arolt V, Pedersen A (2008) Learning potential on the WCST in schizophrenia is related to the neuronal integrity of the anterior cingulate cortex as measured by proton magnetic resonance spectroscopy. Schizophr Res 106:156–163

    PubMed  Google Scholar 

  • Oscar-Berman M (2000) NIAAA Research Monograph No. 34: Neuropsychological vulnerabilites in chronic alcoholism Review of NIAAA’s Neuroscience and Behavioral Research Portfolio. NIAAA, Bethesda, MD, pp 437–472

    Google Scholar 

  • Pan JW, Takahashi K (2005) Interdependence of N-acetyl aspartate and high-energy phosphates in healthy human brain. Ann Neurol 57:92–97

    CAS  PubMed  Google Scholar 

  • Parks MH, Dawant BM, Riddle WR, Hartmann SL, Dietrich MS, Nickel MK, Price RR, Martin PR (2002) Longitudinal brain metabolic characterization of chronic alcoholics with proton magnetic resonance spectroscopy. Alcohol Clin Exp Res 26:1368–1380

    CAS  PubMed  Google Scholar 

  • Parsons OA, Nixon SJ (1998) Cognitive functioning in sober social drinkers: a review of the research since 1986. J Stud Alcohol 59:180–190

    CAS  PubMed  Google Scholar 

  • Pettegrew JW, Kopp SJ, Minshew NJ, Glonek T, Feliksik JM, Tow JP, Cohen MM (1987) 31P nuclear magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: preliminary observations. J Neuropathol.Exp.Neurol 46:419–430

    CAS  PubMed  Google Scholar 

  • Pettegrew JW, Panchalingam K, Withers G, McKeag D, Strychor S (1990) Changes in brain energy and phospholipid metabolism during development and aging in the Fischer 344 rat. J Neuropathol.Exp.Neurol 49:237–249

    CAS  PubMed  Google Scholar 

  • Pfefferbaum A, Sullivan EV, Mathalon DH, Shear PK, Rosenbloom MJ, Lim KO (1995) Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clin Exp Res 19:1177–1191

    CAS  PubMed  Google Scholar 

  • Pfefferbaum A, Adalsteinsson E, Bell RL, Sullivan EV (2007) Development and resolution of brain lesions caused by pyrithiamine- and dietary-induced thiamine deficiency and alcohol exposure in the alcohol-preferring rat: a longitudinal magnetic resonance imaging and spectroscopy study. Neuropsychopharmacology 32:1159–1177

    CAS  PubMed  Google Scholar 

  • Pouwels PJ, Frahm J (1998) Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magn Reson Med 39:53–60

    CAS  PubMed  Google Scholar 

  • Prendergast MA, Harris BR, Mayer S, Littleton JM (2000) Chronic, but not acute, nicotine exposure attenuates ethanol withdrawal-induced hippocampal damage in vitro. Alcohol Clin Exp Res 24:1583–1592

    CAS  PubMed  Google Scholar 

  • Rajkowska G, Selemon LD, Goldman-Rakic PS (1998) Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 55:215–224

    CAS  PubMed  Google Scholar 

  • Riederer F, Bittsansky M, Lehner-Baumgartner E, Baumgartner C, Mlynarik V, Gruber S, Moser E, Kaya M, Serles W (2007) Decrease of NAA with aging outside the seizure focus in mesial temporal lobe epilepsy–a proton-MRS study at 3 Tesla. Brain Res 1179:131–139

    CAS  PubMed  Google Scholar 

  • Romberger DJ, Grant K (2004) Alcohol consumption and smoking status: the role of smoking cessation. Biomed Pharmacother 58:77–83

    CAS  PubMed  Google Scholar 

  • Room R (2004) Smoking and drinking as complementary behaviours. Biomed Pharmacother 58:111–115

    PubMed  Google Scholar 

  • Rosen Y, Lenkinski RE (2007) Recent advances in magnetic resonance neurospectroscopy. Neurotherapeutics 4:330–345

    CAS  PubMed  Google Scholar 

  • Ross B, Bluml S (2001) Magnetic resonance spectroscopy of the human brain. Anat Rec 265:54–84

    CAS  PubMed  Google Scholar 

  • Ross B, Michaelis T (1994) Clinical applications of magnetic resonance spectroscopy. Magn.Reson.Q. 10:191–247

    CAS  PubMed  Google Scholar 

  • Ross AJ, Sachdev PS (2004) Magnetic resonance spectroscopy in cognitive research. Brain Res Brain Res Rev 44:83–102

    CAS  PubMed  Google Scholar 

  • Rothman DL, Petroff OA, Behar KL, Mattson RH (1993a) Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proceedings of the National Academy of Science, U.S.A. 90:5662–5666

    CAS  Google Scholar 

  • Rothman DL, Petroff OAC, Behar KL, Matson RH (1993b) Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci USA 90:5662–5666

    CAS  PubMed  Google Scholar 

  • Rothman DL, Behar KL, Hyder F, Shulman RG (2003) In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu Rev Physiol 65:401–427

    CAS  PubMed  Google Scholar 

  • Sartorius A, Lugenbiel P, Mahlstedt MM, Ende G, Schloss P, Vollmayr B (2008) Proton magnetic resonance spectroscopic creatine correlates with creatine transporter protein density in rat brain. J Neurosci Methods 172:215–219

    CAS  PubMed  Google Scholar 

  • Schuff N, Ezekiel F, Gamst AC, Amend DL, Capizzano AA, Maudsley AA, Weiner MW (2001) Region and tissue differences of metabolites in normally aged brain using multislice 1H magnetic resonance spectroscopic imaging. Magn Reson Med 45:899–907

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schuff N, Meyerhoff DJ, Mueller S, Chao L, Sacrey DT, Laxer K, Weiner MW (2006) N-acetylaspartate as a marker of neuronal injury in neurodegenerative disease. Adv Exp Med Biol 576:241–262 discussion 361-3

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwab ME, Bartholdi D (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 76:319–370

    CAS  PubMed  Google Scholar 

  • Schweinsburg BC, Taylor MJ, Videen JS, Alhassoon OM, Patterson TL, Grant I (2000) Elevated myo-inositol in gray matter of recently detoxified but not long-term alcoholics: A preliminary MR spectroscopy study. Alc Clin Exp Res. 24:699–770

    CAS  Google Scholar 

  • Schweinsburg BC, Taylor MJ, Alhassoon OM, Videen JS, Brown GG, Patterson TL, Berger F, Grant I (2001) 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 25:924–934

    CAS  PubMed  Google Scholar 

  • Seitz D, Widmann U, Seeger U, Nagele T, Klose U, Mann K, Grodd W (1999) Localized proton magnetic resonance spectroscopy of the cerebellum in detoxifing alcoholics. Alcohol Clin Exp Res 23:158–163

    CAS  PubMed  Google Scholar 

  • Selemon LD, Goldman-Rakic PS (1999) The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 45:17–25

    CAS  PubMed  Google Scholar 

  • Simmons ML, Frondoza CG, Coyle JT (1991) Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 45:37–45

    CAS  PubMed  Google Scholar 

  • Spanagel R (2009) Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev 89(2):649–705

    CAS  PubMed  Google Scholar 

  • Steen RG, Hamer RM, Lieberman JA (2005) Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 30:1949–1962

    CAS  PubMed  Google Scholar 

  • Stinson FS, Grant BF, Dawson DA, Ruan WJ, Huang B, Saha T (2005) Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Depend 80:105–116

    PubMed  Google Scholar 

  • Sullivan EV (2000) NIAAA Research Monograph No. 34: Human brain vulnerability to alcoholism: Evidence from neuroimaging studies. In: Noronha A, Eckardt M, Warren K (eds) Review of NIAAA’s neuroscience and behavioral research portfolio. National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, pp 473-508

    Google Scholar 

  • Sullivan EV, Pfefferbaum A (2005) Neurocircuitry in alcoholism: a substrate of disruption and repair. Psychopharmacology (Berl) 180:583–594

    CAS  Google Scholar 

  • Sullivan EV, Rosenbloom M, Serventi KL, Pfefferbaum A (2004) Effects of age and sex on volumes of the thalamus, pons, and cortex. Neurobiol Aging 25:185–192

    PubMed  Google Scholar 

  • Thomson AD, Marshall EJ (2006) The natural history and pathophysiology of Wernicke’s Encephalopathy and Korsakoff’s Psychosis. Alcohol Alcohol 41:151–158

    CAS  PubMed  Google Scholar 

  • Umhau JC, Momenan R, Schwandt ML, Singley E, Lifshitz M, Doty L, Adams LJ, Vengeliene V, Spanagel R, Zhang Y, Shen, George DT, Hommer D, Heilig M (2010) Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals: A Randomized Controlled Experimental Medicine Study. Arch Gen Psychiatry 67:1069-1077

    Google Scholar 

  • Vion-Dury J, Meyerhoff DJ, Cozzone PJ, Weiner MW (1994) What might be the impact on neurology of the analysis of brain metabolism by in vivo magnetic resonance spectroscopy? [editorial]. Journal of Neurology 241:354–371

    CAS  PubMed  Google Scholar 

  • Weber-Fahr W, Ende G, Sartorius A, Spanagel R, Falfan-Melgoza C, Cleppien D, Sommer W (2010) 1H MRS profiling at 9.4T in prefrontal cortex and hippocampus of ethanol dependent rats during intoxication, withdrawal and protracted abstinence ISMRM, Stockholm, Sweden, pp Prog #: 2403

    Google Scholar 

  • Xin L, Mlynarik V, Lei H, Gruetter R (2010) Influence of regional macromolecule baseline on the quantification of neurochemical profile in rat brain ISMRM, Stockholm, Sweden, pp Prog #: 321

    Google Scholar 

  • Yildiz-Yesiloglu A, Ankerst DP (2006a) Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry 30:969–995

    CAS  PubMed  Google Scholar 

  • Yildiz-Yesiloglu A, Ankerst DP (2006b) Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis. Psychiatry Res 147:1–25

    CAS  PubMed  Google Scholar 

  • Zahr NM, Sullivan EV (2008) Translational studies of alcoholism: bridging the gap. Alcohol Res Health 31:215–230

    PubMed  Google Scholar 

  • Zahr NM, Mayer D, Pfefferbaum A, Sullivan EV (2008) Low striatal glutamate levels underlie cognitive decline in the elderly: evidence from in vivo molecular spectroscopy. Cereb Cortex 18:2241–2250

    PubMed  Google Scholar 

  • Zahr NM, Mayer D, Vinco S, Orduna J, Luong R, Sullivan EV, Pfefferbaum A (2009) In vivo evidence for alcohol-induced neurochemical changes in rat brain without protracted withdrawal, pronounced thiamine deficiency, or severe liver damage. Neuropsychopharmacology 34:1427–1442

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zahr NM, Mayer D, Rohlfing T, Hasak MP, Hsu O, Vinco S, Orduna J, Luong R, Sullivan EV, Pfefferbaum A (2010) Brain injury and recovery following binge ethanol: evidence from in vivo magnetic resonance spectroscopy. Biol Psychiatry 67:846–854

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu PJ, Chiappinelli VA (1999) Nicotine modulates evoked GABAergic transmission in the brain. J Neurophysiol 82:3041–3045

    CAS  PubMed  Google Scholar 

  • Zywiak WH, Stout RL, Trefry WB, Glasser I, Connors GJ, Maisto SA, Westerberg VS (2006) Alcohol relapse repetition, gender, and predictive validity. J Subst Abuse Treat 30:349–353

    PubMed  Google Scholar 

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Acknowledgements

This review was supported by NIH R01 AA10788 (DJM), K01 DA24136 (TCD), and grants from the Deutsche Forschungsgemeinschaft (SFB636) (GE) and the Bundesministerium für Bildung und Forschung (BMBF) NGFN-plus (GE).

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Authors and Affiliations

  1. Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA

    Dieter J. Meyerhoff & Timothy C. Durazzo

  2. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA

    Dieter J. Meyerhoff & Timothy C. Durazzo

  3. Department of Neuroimaging, Central Institute of Mental Health, Mannheim, Germany

    Gabriele Ende

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  1. Dieter J. Meyerhoff
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  2. Timothy C. Durazzo
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  3. Gabriele Ende
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Correspondence to Dieter J. Meyerhoff .

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  1. Abt. Psychopharmakologie, Zentralinstitut für Seelische Gesundheit, J 5, Mannheim, 68159, Germany

    Wolfgang H. Sommer

  2. Abt. Psychopharmakologie, Zentralinstitut für Seelische Gesundheit, J 5, Mannheim, 68159, Germany

    Rainer Spanagel

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Meyerhoff, D.J., Durazzo, T.C., Ende, G. (2011). Chronic Alcohol Consumption, Abstinence and Relapse: Brain Proton Magnetic Resonance Spectroscopy Studies in Animals and Humans. In: Sommer, W., Spanagel, R. (eds) Behavioral Neurobiology of Alcohol Addiction. Current Topics in Behavioral Neurosciences, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28720-6_131

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