Download PDF
Fortschr Neurol Psychiatr 2008; 76: S68-S76
DOI: 10.1055/s-2008-1038141
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Neurobiologie stoffgebundener Abhängigkeitserkrankungen - Befunde bildgebender Verfahren[1, ] [2]

Neurobiology of Substance-Related Addiction - Findings of NeuroimagingT.  Kienast1 , J.  Wrase1 , A.  Heinz1
  • 1Klinik für Psychiatrie und Psychotherapie der Charité, CCM, Universitätsmedizin Berlin
Further Information

Publication History

Publication Date:
07 May 2008 (online)

    Permissions and Reprints

Zusammenfassung

Der Einsatz bildgebender Verfahren ermöglicht ein Verständnis grundlegender Mechanismen der Abhängigkeitserkrankungen. Zu den Symptomen einer Abhängigkeitserkrankung gehören die Toleranzentwicklung gegenüber den Substanzwirkungen, Entzugssymptomatik, ein starkes Verlangen nach der Substanz, eine verminderte Kontrolle über den Substanzkonsums und die schädlichen Folgen des Konsums. Bildgebende Studien unterstützen die Hypothese, dass die Ausbildung von Toleranz als homöostatischer Anpassungsprozess an die Wirkung der Droge verstanden werden kann. Beim plötzlichen Entzug der Droge kommt es dann zu einem Verlust der Homöostase, der sich als Entzugssymptomatik zeigt. Die Sensitivierung ist ein der Toleranzentwicklung entgegengesetzter Prozess und beschreibt eine Zunahme der Wirksamkeit einer Substanz bei gleicher Dosierung. Befunde bildgebender Untersuchungen verweisen hier wie bei der Ausbildung des Drogenverlangens auf neuroadaptive Vorgänge im hirneigenen Belohnungssystem. Zu den schädlichen Folgen des Drogenkonsums zählen die neurotoxischen Wirkungen im ZNS. Neben den bildgebenden Befunden zu diesen Kardinalsymptomen der Abhängigkeitserkrankungen diskutieren wir auch bildgebende Studien zu Vulnerabilitätsfaktoren, die zur Entwicklung einer Abhängigkeitserkrankung disponieren.

Abstract

Neuroimaging provides insight into the main biological mechanisms underlying drug and alcohol dependence. Cardinal symptoms of drug dependence are the development of tolerance against drug effects, withdrawal symptoms, drug craving, reduced control over drug intake and harmful consequences of drug consumption. Brain imaging studies support the hypothesis that tolerance development can be understood as a neuroadaptive mechanism to ensure homeostasis during chronic drug intake. When drug consumption is suddenly interrupted during detoxification, the loss of homeostasis can manifest as a withdrawal syndrome. While tolerance development reduces the effects of chronic drug intake, sensitization is a neuroadaptive process that increases the effects of a drug dose. Brain imaging studies indicate that sensitisation and drug craving are associated with neuroadaptive processes in the brain reward system. Harmful consequences of drug intake include neurotoxic effects on the central nervous system. Besides discussing brain imaging studies on the neurobiological correlates of drug dependence, this review also presents studies on vulnerability factors that predispose individuals to excessive drug intake.

Schlüsselwörter

Abhängigkeitserkrankung - Neurobiologie - Funktionelle Bildgebung

Key words

addiction - neurobiology - neuroimaging

1 Mit Unterstürzung der DFG (He 2597/4-2 & 7-2)

2 Erstveröffentlichung im 31. Band „Fortschritt und Fortbildung in der Medizin” 2007/2008 der Bundesärztekammer (ISSN 0170-3331).

Literatur

  • 1 Volkow N D, Fowler J S, Wang G. The addicted human brain: insights from imaging studies.  J Clin Invest. 2003;  111 1444-1451
    Google Scholar
  • 2 Jacobsen L K, Giedd J N, Gottschalk C, Kosten T R, Krystal J H. Quantitative morphology of the caudate and putamen in patients with cocaine dependence.  Am J Psychiatry. 2001;  158 486-489
    Google Scholar
  • 3 Kienast T, Heinz A. Suchterkrankungen. In: Walter H (Hrsg). Funktionelle Bildgebung in Psychiatrie und Psychotherapie. Stuttgart: Schattauer Verlag 2004
    Google Scholar
  • 4 Koob G F, Le Moal M. Drug abuse: hedonic homeostatic dysregulation.  Science. 1997;  278 52-58
    Google Scholar
  • 5 Grant J E, Brewer J A, Potenza M N. The neurobiology of substance and behavioral addictions.  CNS Spectr. 2006;  11 924-930
    Google Scholar
  • 6 Heinz A, Batra A. Neurobiologie der Alkohol und Nikotinabhängigkeit. In: Brandt, Cohen, Helmchen, Schmidt (Hrsg). Psychiatrie, Neurologie, Klinische Psychologie- Stuttgart: Kohlhamer Verlag 2003
    Google Scholar
  • 7 Kienast T, Heinz A. Dopamine and the diseased brain.  CNS Neurol Disord Drug Targets. 2006;  5 09-131
    Google Scholar
  • 8 McClung C A. The molecular mechanisms of morphine addiction.  Rev Neurosci. 2006;  17 393-402
    Google Scholar
  • 9 Noble F, Cox B M. Differential desensitization of μ- and δ-opioid receptors in selected neural pathways following chronic morphine treatment.  Br J Pharmacol. 1996;  117 161-169
    Google Scholar
  • 10 Devine D P, Leone P, Pocock D, Wise R A. Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies.  J Pharmacol Exp Ther. 1993;  266 1236-1246
    Google Scholar
  • 11 Wang G J, Volkow N D, Fowler J S, Logan J, Abumrad N N, Hitzemann R J, Pappas N S, Pascani K. Dopamine D2-receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal.  Neuropsychopharmacology. 1997;  16 174-182
    Google Scholar
  • 12 Diana M, Muntoni A L, Pistis M, Melis M, Gessa G L. Lasting reduction in mesolimbic dopamine neuronal activity after morphine withdrawal.  Eur J Neurosci. 1999;  11 1037-1041
    Google Scholar
  • 13 Dyck C H van, Rosen M I, Thomas H M, McMahon T J, Wallace E A, O'Connor P G, Sullivan M, Krystal J H, Hoffer P B, Woods S W. SPECT regional cerebral blood flow alterations in naltrexone precipitated withdrawal from buprenorphine.  Psychiatry Res. 1994;  55 181-191
    Google Scholar
  • 14 Krystal J H, Woods S W, Kosten T R, Rosen M I, Seibyl J P, Dyck C C van, Price L H, Zubal I G, Hoffer P B, Charney D S. Opiate dependence and withdrawal: preliminary assessment using single photon emission computerized tomography (SPECT).  Am J Drug Alcohol Abuse. 1995;  21 47-63
    Google Scholar
  • 15 Rose R J, Branchey M J, Buydens-Branchey L, Stapleton J M, Chasten K, Werrell A, Maayan M L. Cerebral perfusion in early and latae opiate withdrawal: a technetium-99m-HMPAO SPECT study.  Psychiatry Res. 1996;  67 39-47
    Google Scholar
  • 16 Volkow N D, Fowler J S, Wang G J, Hitzemann R, Logan J, Schlyer D J, Dewey S L, Wolf A P. Decreased dopamine D2-receptor availability is associated with reduced frontal metabolism in cocaine abusers.  Synapse. 1993;  14 169-177
    Google Scholar
  • 17 Williams J M, Galli A. The dopamine transporter: a vigilant border control for psychostimulant action.  Handb Exp Pharmacol. 2006;  175 215-232
    Google Scholar
  • 18 Howell L L, Hoffmann J M, Votaw J R, Landrum A M, Wilcox K M, Lindsey K P. Cocaine-induced brain activation determined by positron emission tomography neuroimaging in conscious rhesus monkeys.  Psychopharmacology. 2003;  159 154-160
    Google Scholar
  • 19 Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, Yoshikawa E, Futatsubashi M, Takei N, Mori N. Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.  Am J Psychiatry. 2001;  158 1206-1214
    Google Scholar
  • 20 Paulus M P, Hozack N E, Zauscher B E, Frank L, Brown G G, Braff D L, Schuckit M A. Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects.  Neuropsychopharmacology. 2002;  26 53-63
    Google Scholar
  • 21 Chang L, Grob C S, Ernst T, Itti L, Mishkin F S, Jose-Melchor R, Poland R E. Effect of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a co-registered SPECT and MRI study.  Psychiatry Res. 2000;  98 15-28
    Google Scholar
  • 22 Hu Y, Lund I V, Gravielle M C, Farb D H, Brooks-Kayal A R, Russek S J. Surface expression of GABA (A) receptors is transcriptionally controlled by the interplay of CREB and its binding partner ICER. J Biol Chem 2008 Epub ahead of print
    Google Scholar
  • 23 Carpenter-Hyland E P, Chandler L J. daptive plasticity of NMDA receptors and dendritic spines: implications for enhanced vulnerability of the adolescent brain to alcohol addiction.  Pharmacol Biochem Behav. 2007;  86 200-208
    Google Scholar
  • 24 Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Grusser S M, Flor H, Braus D F, Buchholz H G, Gründer G, Schreckenberger M, Smolka M N, Roesch F, Mann K, Bartenstein P. Correlation between dopamine D2-receptors in the ventral striatum and central processing of alcohol cues and craving.  Am J Psychiatry. 2004;  161 1783-1789
    Google Scholar
  • 25 Heinz A, Dufeu P, Kuhn S, Dettling M, Graf K, Kurten I, Rommelspacher H, Schmidt L G. Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients.  Arch Gen Psychiatry. 1996;  53 123-1128
    Google Scholar
  • 26 Heinz A, Goldman D. Genotype effects on neurodegeneration and neuroadaptation in monoaminergic neurotransmitter systems.  Neurochem Int. 2000;  37 425-432
    Google Scholar
  • 27 Budney A J, Hughes J R, Moore B A, Novy P L. Marijuana abstinence effects in marijuana smokers maintained in their home environment.  Arch Gen Psychiatry. 2001;  58 917-924
    Google Scholar
  • 28 Iversen L. Cannabis and the brain.  Brain. 2003;  126 1252-1270
    Google Scholar
  • 29 Dagher A, Bleicher C, Aston J A, Gunn R N, Clarke P B. Reduces dopamine D1-receptor binding in the ventral striatum of cigarette smokers.  Synapse. 2001;  42 48-53
    Google Scholar
  • 30 Fowler J S, Wang G J, Volkow N D, Franceschi D, Logan J, MacGregor R R, Garza V. Smoking a single cigarette does not produce a measurable reduction in brain MAO B in non smokers.  Nicotine & Tobacco Research. 1999;  1 325-329
    Google Scholar
  • 31 Stead L, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation.  Cochrane Database Syst Rev. 2008;  1 CD000146
    Google Scholar
  • 32 Jorenby D E, Leischow S J, Nides M A, Rennard S I, Johnston J A, Hughes A R, Smith S S, Muramoto M L, Daughton D M, Doan K, Fiore M C, Baker T. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.  N Engl J Med. 1999;  340 685-689
    Google Scholar
  • 33 Robinson T E, Berridge K C. Addiction.  Annu Rev Psychol. 2003;  54 25-53
    Google Scholar
  • 34 Tiffany S T. Cognitive concepts of craving.  Alcohol Res Health. 1999;  23 215-224
    Google Scholar
  • 35 Breiter H C, Rauch S L, Kwong K K, Baker J R, Weisskoff R M, Kennedy D N, Kendrick A D, Davis T L, Jiang A, Cohen M S, Stern C E, Belliveau J W, Baer L, O'Sullivan R L, Savage C R, Jenike M A, Rosen B R. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.  Arch Gen Psychiatry. 1996;  53 595-606
    Google Scholar
  • 36 Weiss F. Neurobiology of craving, conditioned reward and relapse.  Curr Opin Pharmacol. 2005;  5 9-19
    Google Scholar
  • 37 Weinstein A, Feldtkeller B, Malizia A, Wilson S, Bailey J, Nutt D J. Integrating the cognitive and physiological aspects of craving.  J Psychopharmacol. 1998;  12 31-38
    Google Scholar
  • 38 Wexler B E, Gottschalk C H, Fulbright R K, Prohovnik I, Lacadie C M, Rounsaville B J, Gore J C. Functional magnetic resonance imaging of cocaine craving.  Am J Psychiatry. 2001;  158 86-95
    Google Scholar
  • 39 Childress A R, Mozley P D, McElgin W, Fitzgerald J, Reivich M, O'Brien C P. Limbic activation during cue-induced cocaine craving.  Am J Psychiatry. 1999;  56 11-18
    Google Scholar
  • 40 Grant S, London E D, Newlin D B, Villemagne V L, Liu X, Contoreggi C, Phillips R L, Kimes A S, Margolin A. Activation of memory circuits during cue-elicited cocaine craving.  Proc Natl Acad Sci USA. 1996;  93 12 040-12 045
    Google Scholar
  • 41 Maas L C, Lukas S E, Kaufman M J, Weiss R D, Daniels S L, Rogers V W, Kukes T J, Renshaw P F. Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving.  Am J Psychiatry. 1998;  155 124-126
    Google Scholar
  • 42 London E D, Ernst M, Grant S, Bonson K, Weinstein A. Orbitofrontal cortex and human drug abuse: functional imaging.  Cereb Cortex. 2000;  10 334-342
    Google Scholar
  • 43 Lingford-Hughes A R, Davies S J, McIver S, Williams T M, Daglish M R, Nutt D J. Addiction.  Br Med Bull. 2003;  65 209-222
    Google Scholar
  • 44 Boettiger C A, Mitchell J M, Tavares V C, Robertson M, Joslyn G, D'Esposito M, Fields H L. Immediate reward bias in humans: fronto-parietal networks and a role for the catechol-O-methyltransferase 158(Val/Val) genotype.  J Neurosci. 2007;  27 14 383-14 391
    Google Scholar
  • 45 Garavan H, Pankiewicz J, Bloom A, Cho J K, Sperry L, Ross T J, Salmeron B J, Risinger R, Kelley D, Stein E A. Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli.  Am J Psychiatry. 2000;  157 1789-1798
    Google Scholar
  • 46 Schneider F, Habel U, Wagner M, Franke P, Salloum J B, Shah N J, Toni I, Sulzbach C, Honig K, Maier W, Gaebel W, Zilles K. Subcortical correlates of craving in recently abstinent alcoholic patients.  Am J Psychiatry. 2001;  158 1075-1083
    Google Scholar
  • 47 Grüsser S M, Heinz A, Flor H. Standardized stimuli to assess drug craving and drug memory in addicts.  J Neural Transm. 2000;  107 715-720
    Google Scholar
  • 48 George M S, Anton R F, Bloomer C, Teneback C, Drobes D J, Lorberbaum J P, Nahas Z, Vincent D J. Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.  Arch Gen Psychiatry. 2001;  58 345-352
    Google Scholar
  • 49 Braus D F, Wrase J, Grusser S, Hermann D, Ruf M, Flor H, Mann K, Heinz A. Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics.  J Neural Transm. 2001;  108 887-894
    Google Scholar
  • 50 Myrick H, Anton R F, Li X, Henderson S, Drobes D, Voronin K, George M S. Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving.  Neuropsychopharmacology. 2004;  29 393-402
    Google Scholar
  • 51 Wrase J, Schlagenhauf F, Kienast T, Wüstenberg T, Bermpohl F, Kahnt T, Beck A, Ströhle A, Juckel G, Knutson B, Heinz A. Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics.  Neuroimage. 2007;  35 787-794
    Google Scholar
  • 52 Grusser S M, Wrase J, Klein S, Hermann D, Smolka S M, Ruf M, Weber-Fahr W, Flor H, Mann K, Braus D F, Heinz A. Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics.  Psychopharmacology. 20;  175 296-302
    Google Scholar
  • 53 Garavan H, Ross T J, Stein E A. Right hemispheric dominance of inhibitory control: an event-related functional MRI study.  Proc Natl Acad Sci USA. 1999;  96 8301-8306
    Google Scholar
  • 54 Royall D R, Lauterbach E C, Cummings J L, Reeve A, Rummans T A, Kaufer D I, LaFrance Jr W C, Coffey C E. Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association.  J Neuropsychiatry Clin Neurosci. 2002;  14 377-405
    Google Scholar
  • 55 Volkow N D, Fowler J S. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex.  Cereb Cortex. 2000;  10 318-325
    Google Scholar
  • 56 Goldstein R Z, Volkow N D. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex.  Am J Psychiatry. 2002;  159 1642-1652
    Google Scholar
  • 57 Mansvelder H D, Aerde K I van, Couey J J, Brussaard A B. Nicotinic modulation of neuronal networks: from receptors to cognition.  Psychopharmacology (Berl). 2006;  184 292-305
    Google Scholar
  • 58 Ernst M, Matochik J A, Heishman S J, Horn J D van, Jons P H, Henningfield J E, London E D. Effect of nicotine on brain activation during performance of a working memory task.  Proc Natl Acad Sci USA. 2001;  98 4728-4733
    Google Scholar
  • 59 Heinz A, Higley J D, Gorey J G, Saunders R C, Jones D W, Hommer D, Zajicek K, Suomi S J, Lesch K P, Weinberger D R, Linnoila M. In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates.  Am J Psychiatry. 1998;  155 1023-1028
    Google Scholar
  • 60 Izquierdo A, Newman T K, Higley J D, Murray E A. Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys.  Proc Natl Acad Sci U S A. 2007;  104 14 128-14 133
    Google Scholar
  • 61 Heinz A, Jones D W, Gorey J G, Bennet A, Suomi S J, Weinberger D R, Higley J D. Serotonin transporter availability correlates with alcohol intake in non-human primates.  Mol Psychiatry. 2003;  8 231-234
    Google Scholar
  • 62 Schuckit M A, Smith T L. An 8-year follow-up of 4 sons of alcoholic and control subjects.  Arch Gen Psychiatry. 1996;  53 202-221
    Google Scholar
  • 63 Schuckit M A. New findings in the genetics of alcoholism.  JAMA. 1999;  281 1875-1876
    Google Scholar
  • 64 Volkow N D, Wang G J, Fowler J S, Logan J, Gatley S J, Gifford A, Hitzemann R, Ding Y S, Pappas N. Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2-receptor levels.  Am J Psychiatry. 1999;  156 1440-1443
    Google Scholar
  • 65 Papp M, Klimek V, Willner P. Parallel changes in dopamine D2-receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine.  Psychopharmacology. 1994;  115 441-446
    Google Scholar
  • 66 Martin M, Hurley R A, Taber K H. Is opiate addiction associated with longstanding neurobiological changes?.  J Neuropsychiatry Clin Neurosci. 2007;  19 242-248
    Google Scholar
  • 67 Gacouin A, Lavoue S, Signouret T, Person A, Dinard M D, Shpak N, Thomas R. Reversible spongiform leucoencephalopathy after inhalation of heated heroin.  Intensive Care Med. 2003;  29 1012-1015
    Google Scholar
  • 68 Christensen J D, Kaufman M J, Levin J M, Mendelson J H, Holman B L, Cohen B M, Renshaw P F. Abnormal cerebral metabolism in polydrug abusers during early withdrawal: a 31P MR spectroscopy study.  Magn Reson Med. 1996;  35 658-663
    Google Scholar
  • 69 Silveri M M, Pollack M H, Diaz C I, Nassar L E, Mendelson J H, Yurgelun-Todd D A, Renshaw P F, Kaufman M J. Cerebral phosphorus metabolite and transverse relaxation time abnormalities in heroin-dependent subjects at onset of methadone maintenance treatment.  Psychiatry Res. 2004;  131 217-226
    Google Scholar
  • 70 Franklin T R, Acton P D, Maldjian J A, Gray J D, Croft J R, Dackis C A, O'Brien C P, Childress A R. Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients.  Biol Psychiatry. 2002;  51 34-142
    Google Scholar
  • 71 Lyons D, Friedman D P, Nader M A, Porrino L J. Cocaine alters cerebral metabolism within the ventral striatum and limbic cortex of monkeys.  J Neurosci. 1996;  16 1230-1238
    Google Scholar
  • 72 Jacobsen L K, Giedd J N, Gottschalk C, Kosten T R, Krystal J H. Quantitative morphology of the caudate and putamen in patients with cocaine dependence.  Am J Psychiatry. 2001;  158 486-489
    Google Scholar
  • 73 Gouzoulis-Mayfrank E, Daumann J. Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage?.  Addiction. 2006;  101 348-361
    Google Scholar
  • 74 Martinsson L, Hardemark H, Eksborg S. Amphetamines for improving recovery after stroke.  Cochrane Database Syst Rev. 2007;  1 CD002090
    Google Scholar
  • 75 Hatzidimitriou G, McCann D U, Ricuarte G A. Altered serotonin innervation patterns in the forebrain of monkeys treated with 3,4-methylendioxymethamphetamine seven years previously: factors influencing abnormal recovery.  J Neurosci. 1999;  19 5096-5107
    Google Scholar
  • 76 Ricaurte G A, Yuan J, Hatzidimitriou G, Cord B J, McCann D U. Retraction.  Science. 2003;  301 1479
    Google Scholar
  • 77 Heinz A, Jones D W. Serotonin transporters in ecstasy users.  Br J Psychiatry. 2000;  176 193
    Google Scholar
  • 78 Thomasius R, Petersen K, Buchert R, Andresen B, Zapletalova P, Wartberg L, Nebeling B, Schmoldt A. Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users.  Psychopharmacology (Berl). 2003;  167 85-96
    Google Scholar
  • 79 Buchert R, Obrocki J, Thomasius R, Vaterlein O, Petersen K, Jenicke L, Bohuslavizki K H, Clausen M. Long-term effects of “ecstasy” use on serotonin transporters of the brain investigated by PET.  J Nucl Med. 2003;  44 375-384
    Google Scholar
  • 80 Mann K, Agartz I, Harper C, Shoaf S, Rawlings R R, Momenan R, Hommer D W, Pfefferbaum A, Sullivan E V, Anton R F, Drobes D J, George M S, Bares R, Machulla H J, Mundle G, Reimold M, Heinz A. Neuroimaging in alcoholism: ethanol and brain damage.  Alcohol Clin Exp Res. 2001;  25 (5 Suppl ISBRA) 104S-109S
    Google Scholar
  • 81 Pfefferbaum A, Sullivan E V, Mathalon D H, Shear P K, Rosenbloom M J, Lim K O. Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics.  Alcohol Clin Exp Res. 1995;  19 1177-1191
    Google Scholar
  • 82 Sullivan E V, Marsh L, Mathalon D H, Lim K O, Pfefferbaum A. Relationship between alcohol withdrawal seizures and temporal lobe white matter volume deficits.  Alcohol Clin Exp Res. 1996;  20 348-354
    Google Scholar
  • 83 Agartz I, Momenan R, Rawlings R R, Kerich M J, Hommer D W. Hippocampal volume in patients with alcohol dependence.  Arch Gen Psychiatry. 1999;  56 356-363
    Google Scholar
  • 84 Hommer D, Momenan R, Rawlings R, Ragan P, Williams W, Rio D, Eckardt M. Decreased corpus callosum size among alcoholic women.  Arch Neurol. 1996;  53 359-363
    Google Scholar
  • 85 Bendszus M, Weijers H G, Wiesbeck G, Warmuth-Metz M, Bartsch A J, Engels S, Boning J, Solymosi L. 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. 2001;  22 926-1932
    Google Scholar
  • 86 Heinz A, Ragan P, Jones D W, Hommer D, Williams W, Knable M B, Gorey J G, Doty L, Geyer C, Lee K S, Coppola R, Weinberger D R, Linnoila M. Reduced central serotonin transporters in alcoholism.  Am J Psychiatry. 1998;  155 1544-1549
    Google Scholar
  • 87 Heinz A, Jones D W, Bissette G, Hommer D, Ragan P, Knable M, Wellek S, Linnoila M, Weinberger D R. Relationship between cortisol and serotonin metabolites and transporters in alcoholism [correction of alcolholism].  Pharmacopsychiatry. 2002;  35 127-134
    Google Scholar
  • 88 Sullivan E V, Lane B, Deshmukh A, Rosenbloom M J, Desmond J E, Lim K O, Pfefferbaum A. In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics.  Alcohol Clin Exp Res. 1999;  23 1629-1636
    Google Scholar
  • 89 Landfield P W, Cadwallader L B, Vinsant S. Quantitative changes in hippocampal structure following long-term exposure to delta 9-tetrahydrocannabinol: Possible mediation by glucocorticoid systems.  Brain res. 1988;  443 47-62
    Google Scholar
  • 90 Heath R G, Fitzjarrell A T, Fontana C J, Garey R E. Cannabis sativa: effects on brain function and ultrastructure in rhesus monkeys.  Biol Psychiatry. 1980;  15 657-690
    Google Scholar
  • 91 Chan G C, Hinds T R, Impey S, Storm D R. Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol.  J Neurosci. 1998;  18 5322-5332
    Google Scholar
  • 92 Fletcher J M, Page J B, Francis D J, Copeland K, Naus M J, Davis C M, Morris R, Krauskopf D, Satz P. Cognitive correlates of long-term cannabis use in Costa Rican men.  Arch Gen Psychiatry. 1996;  53 1051-1057
    Google Scholar
  • 93 Sarne Y, Mechoulam R. Cannabinoids: between neuroprotection and neurotoxicity.  Curr Drug Targets CNS Neurol Disord. 2005;  4 677-684
    Google Scholar

1 Mit Unterstürzung der DFG (He 2597/4-2 & 7-2)

2 Erstveröffentlichung im 31. Band „Fortschritt und Fortbildung in der Medizin” 2007/2008 der Bundesärztekammer (ISSN 0170-3331).

Prof. Dr. med. Andreas Heinz

Klinik für Psychiatrie und Psychotherapie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin

Charitéplatz 1

10117 Berlin

Email: andreas.heinz@charite.de

      >