Download PDF
Der Nuklearmediziner 2002; 25(3): 157-164
DOI: 10.1055/s-2002-34110
Benzodiazepinrezeptoren

© Georg Thieme Verlag Stuttgart · New York

Der GABA-A-Benzodiazepinrezeptorkomplex: Rolle von PET und SPECT in Neurologie und Psychiatrie

The GABA-A Benzodiazepine Receptor Complex: Role of PET and SPECT in Neurology and PsychiatryF. D. Juengling1 , M. Schäfer2 , A. Heinz2
  • 1Abteilung für Nuklearmedizin, Radiologie III, Universitätsklinik Ulm
  • 2Klinik für Psychiatrie und Psychotherapie, Charité, Humboldt-Universität zu Berlin
Further Information

Publication History

Publication Date:
16 September 2002 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Mit der Entwicklung selektiver Liganden für den GABA-A-Benzodiazepinrezeptorkomplex (GBZR) hat die nuklearmedizinische Bildgebung mittels Positronen-Emissionstomographie (PET) und Single-Photon-Emissionscomputertomographie (SPECT) einen festen Stellenwert für Klinik und Forschung in der Neurologie und Psychiatrie erlangt. Die vorliegende Überblicksarbeit fasst den aktuellen Wissensstand von Anwendungsmöglichkeiten und -grenzen der nuklearmedizinischen Bildgebung der GBZR in vivo zusammen und beleuchtet ihren klinischen Nutzen. Die wachsende Bedeutung für das Verständnis der Pathophysiologie und pharmakotherapeutischer Konzepte unterschiedlicher psychiatrischer Erkrankungen wird herausgestellt.

Abstract

Nuclear medicine imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) for selective depiction of GABA-A-benzodiazepine receptor (GBZR) binding are complementary investigations in the diagnostic process of neurological and psychiatric disorders. This review summarizes the current knowledge about options and limitations of PET and SPECT for in vivo diagnostics in neurology and psychiatry. The growing importance of GBZR-imaging for the understanding of pathophysiology and pharmacological treatment in different psychiatric syndromes is discussed.

Schlüsselwörter

GABA-A-Benzodiazepinrezeptor - Flumazenil - Iomazenil - Epilepsie - PTSD - Panikstörung - Alkoholkrankheit - Schizophrenie

Key words

GABA-A-benzodiazepine-receptor - Flumazenil - Iomazenil - Epilepsy - PTSD - Panic Disorder - Alcoholism - Schizophrenia

Literatur

  • 1 MaziÉre M, Prenant C, Sastre J, Crouzel M, Comar D, Hantraye P. et al . 11C-Ro 15-1788 et 11C-flunitrazepam, deux coordinats pour l'etude par tomographie par positons des sites de liaison des benzodiazepines.  C R Seances Acad Sci III. 1983;  296 871-876
    PubMedGoogle Scholar
  • 2 Grunder G, Siessmeier T, Lange-Asschenfeldt C, Vernaleken I, Buchholz H G, Stoeter P. et al . [18F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors.  Eur J Nucl Med. 2001;  28 1463-1470
    CrossrefPubMedGoogle Scholar
  • 3 Moerlein S M, Perlmutter J S. Binding of 5-(2′-[18F]fluoroethyl)flumazenil to central benzodiazepine receptors measured in living baboon by positron emission tomography.  Eur J Pharmacol. 1992;  218 109-115
    CrossrefPubMedGoogle Scholar
  • 4 Savic I, Persson A, Roland P, Pauli S, Sedvall G, Widen L. In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci.  Lancet. 1988;  2 863-866
    PubMedGoogle Scholar
  • 5 Juhasz C, Chugani D C, Muzik O, Watson C, Shah J, Shah A. et al . Electroclinical correlates of flumazenil and fluorodeoxyglucose PET abnormalities in lesional epilepsy.  Neurology. 2000;  55 825-835
    PubMedGoogle Scholar
  • 6 Koepp M J, Hammers A, Labbe C, Woermann F G, Brooks D J, Duncan J S. 11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI.  Neurology. 2000;  54 332-339
    CrossrefPubMedGoogle Scholar
  • 7 Nagy F, Chugani D C, Juhasz C, da Silva E A, Muzik O, Kupsky W. et al . Altered in vitro and in vivo flumazenil binding in human epileptogenic neocortex.  J Cereb Blood Flow Metab. 1999;  19 939-947
    PubMedGoogle Scholar
  • 8 Szelies B, Sobesky J, Pawlik G, Mielke R, Bauer B, Herholz K. et al . Impaired benzodiazepine receptor binding in peri-lesional cortex of patients with symptomatic epilepsies studied by [(11)C]-flumazenil PET.  Eur J Neurol. 2002;  9 137-142
    CrossrefPubMedGoogle Scholar
  • 9 Kim J H, Tien R D, Felsberg G J, Osumi A K, Lee N, Friedman A H. Fast spin-echo MR in hippocampal sclerosis: correlation with pathology and surgery.  AJNR Am J Neuroradiol. 1995;  16 627-636
    PubMedGoogle Scholar
  • 10 Henry T R, Frey K A, Sackellares J C, Gilman S, Koeppe R A, Brunberg J A. et al . In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy.  Neurology. 1993;  43 1998-2006
    PubMedGoogle Scholar
  • 11 Koepp M J, Richardson M P, Brooks D J, Poline J B, Van-Paesschen W, Friston K J. et al . Cerebral benzodiazepine receptors in hippocampal sclerosis. An objective in vivo analysis.  Brain. 1996;  119 1677-1687
    PubMedGoogle Scholar
  • 12 Szelies B, Weber-Luxenburger G, Mielke R, Pawlik G, Kessler J, Pietrzyk U. et al . Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry.  Eur J Neurol. 2000;  7 393-400
    CrossrefPubMedGoogle Scholar
  • 13 Feeney D M, Baron J C. Diaschisis.  Stroke. 1986;  17 817-830
    CrossrefPubMedGoogle Scholar
  • 14 Juhasz C, Chugani D C, Muzik O, Watson C, Shah J, Shah A. et al . Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?.  Ann Neurol. 2000;  48 88-96
    CrossrefPubMedGoogle Scholar
  • 15 Koutroumanidis M, Binnie C D, Elwes R D, Polkey C E, Seed P, Alarcon G. et al . Interictal regional slow activity in temporal lobe epilepsy correlates with lateral temporal hypometabolism as imaged with 18FDG PET: neurophysiological and metabolic implications.  J Neurol Neurosurg Psychiatry. 1998;  65 170-176
    PubMedGoogle Scholar
  • 16 Juhasz C, Behen M E, Muzik O, Chugani D C, Chugani H T. Bilateral medial prefrontal and temporal neocortical hypometabolism in children with epilepsy and aggression.  Epilepsia. 2001;  42 991-1001
    CrossrefPubMedGoogle Scholar
  • 17 Juengling F D, Kassubek J, Otte A. Standardization of cerebral PET imaging in clinical neurological diagnostics.  Eur J Nucl Med. 2000;  27 98
    PubMedGoogle Scholar
  • 18 Richardson M P, Friston K J, Sisodiya S M, Koepp M J, Ashburner J, Free S L. et al . Cortical grey matter and benzodiazepine receptors in malformations of cortical development. A voxel-based comparison of structural and functional imaging data.  Brain. 1997;  120 1961-1973
    CrossrefPubMedGoogle Scholar
  • 19 Koepp M J, Richardson M P, Labbe C, Brooks D J, Cunningham V J, Ashburner J. et al . 11C-flumazenil PET, volumetric MRI, and quantitative pathology in mesial temporal lobe epilepsy.  Neurology. 1997;  49 764-773
    PubMedGoogle Scholar
  • 20 Hammers A, Koepp M J, Labbe C, Brooks D J, Thom M, Cunningham V J. et al . Neocortical abnormalities of [11C]-flumazenil PET in mesial temporal lobe epilepsy.  Neurology. 2001;  56 897-906
    PubMedGoogle Scholar
  • 21 Koepp M J, Labbe C, Richardson M P, Brooks D J, Van Paesschen W, Cunningham V J. et al . Regional hippocampal [11C]flumazenil PET in temporal lobe epilepsy with unilateral and bilateral hippocampal sclerosis.  Brain. 1997;  120 1865-1876
    CrossrefPubMedGoogle Scholar
  • 22 Hand K S, Baird V H, Van-Paesschen W, Koepp M J, Revesz T, Thom M. et al . Central benzodiazepine receptor autoradiography in hippocampal sclerosis.  Br J Pharmacol. 1997;  122 358-364
    CrossrefPubMedGoogle Scholar
  • 23 Koepp M J, Hand K S, Labbe C, Richardson M P, Van-Paesschen W, Baird V H. et al . In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis.  Ann Neurol. 1998;  43 618-626
    CrossrefPubMedGoogle Scholar
  • 24 Desbiens R, Berkovic S F, Dubeau F, Andermann F, Laxer K D, Harvey S. et al . Life threatening focal status epilepticus due to occult cortical dysplasia.  Arch Neurol. 1993;  50 695-700
    CrossrefPubMedGoogle Scholar
  • 25 Arnold S, Berthele A, Drzezga A, Tolle T R, Weis S, Werhahn K J. et al . Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia.  Epilepsia. 2000;  41 818-824
    PubMedGoogle Scholar
  • 26 Bouilleret V, Dupont S, Spelle L, Baulac M, Samson Y, Semah F. Insular cortex involvement in mesiotemporal lobe epilepsy: a positron emission tomography study.  Ann Neurol. 2002;  51 202-208
    CrossrefPubMedGoogle Scholar
  • 27 Richardson M P, Koepp M J, Brooks D J, Fish D R, Duncan J S. Benzodiazepine receptors in focal epilepsy with cortical dysgenesis: an 11C-flumazenil PET study.  Ann Neurol. 1996;  40 188-198
    CrossrefPubMedGoogle Scholar
  • 28 Hammers A, Koepp M J, Richardson M P, Labbe C, Brooks D J, Cunningham V J. et al . Central benzodiazepine receptors in malformations of cortical development: A quantitative study.  Brain. 2001;  124 1555-1565
    CrossrefPubMedGoogle Scholar
  • 29 Bartenstein P, Ludolph A, Schober O, Lottes G, Scheidhauer K, Sciuk J. et al . Benzodiazepine receptors and cerebral blood flow in partial epilepsy.  Eur J Nucl Med. 1991;  18 111-118
    PubMedGoogle Scholar
  • 30 Savic I, Thorell J O, Roland P. [11C]flumazenil positron emission tomography visualizes frontal epileptogenic regions.  Epilepsia. 1995;  36 1225-1232
    CrossrefPubMedGoogle Scholar
  • 31 Richardson M P, Koepp M J, Brooks D J, Duncan J S. 11C-flumazenil PET in neocortical epilepsy.  Neurology. 1998;  51 485-492
    PubMedGoogle Scholar
  • 32 Winkler P A, Herzog C, Henkel A, Arnold S, Werhahn K J, Yousry T A. et al . Nichtinvasives Protokoll für die epilepsiechirurgische Behandlung fokaler Epilepsien.  Nervenarzt. 1999;  70 1088-1093
    CrossrefPubMedGoogle Scholar
  • 33 Juhasz C, Chugani D C, Muzik O, Shah A, Shah J, Watson C. et al . Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome.  Neurology. 2001;  56 1650-1658
    CrossrefPubMedGoogle Scholar
  • 34 Tanaka F, Yonekura Y, Ikeda A, Terada K, Mikuni N, Nishizawa S. et al . Presurgical identification of epileptic foci with iodine-123 iomazenil SPET: comparison with brain perfusion SPET and FDG PET.  Eur J Nucl Med. 1997;  24 27-34
    CrossrefPubMedGoogle Scholar
  • 35 Venz S, Hierholzer J, Cordes M, Straub H B, Keske U, Meencke H J. et al . Quantitative estimation of I-123-Iomazenil receptor binding in temporal lobe epilepsies using two SPECT acquisitions-comparison with the regional cerebral blood flow and a compartment model.  Nuklearmedizin. 1998;  37 49-56
    PubMedGoogle Scholar
  • 36 Bremner J D, Baldwin R, Horti A, Staib L H, Ng C K, Tan P Z. et al . Quantitation of benzodiazepine receptor binding with PET [11C]iomazenil and SPECT [123I]iomazenil: preliminary results of a direct comparison in healthy human subjects.  Psychiatry Res. 1999;  91 79-91
    PubMedGoogle Scholar
  • 37 Bremner J D, Horti A, Staib L H, Zea-Ponce Y, Soufer R, Charney D S. et al . Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [(11)C]Iomazenil in healthy human subjects.  Synapse. 2000;  35 68-77
    CrossrefPubMedGoogle Scholar
  • 38 Millet P, Graf C, Buck A, Walder B, Westera G, Broggini C. et al . Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors.  J Cereb Blood Flow Metab. 2000;  20 1587-1603
    PubMedGoogle Scholar
  • 39 Heiss W D, Kracht L, Grond M, Rudolf J, Bauer B, Wienhard K. et al . Early [(11)C]Flumazenil/H(2)O positron emission tomography predicts irreversible ischemic cortical damage in stroke patients receiving acute thrombolytic therapy.  Stroke. 2000;  31 366-369
    PubMedGoogle Scholar
  • 40 Odano I, Miyashita K, Minoshima S, Nakajima T, Fujita M, Takahashi N. et al . A potential use of a 123I-labelled benzodiazepine receptor antagonist as a predictor of neuronal cell viability: comparisons with 14C-labelled 2-deoxyglucose autoradiography and histopathological examination.  Nucl Med Commun. 1995;  16 443-446
    PubMedGoogle Scholar
  • 41 Lloyd C M, Richardson M P, Brooks D J, Al-Chalabi A, Leigh P N. Extramotor involvement in ALS: PET studies with the GABA(A) ligand [(11)C]flumazenil.  Brain. 2000;  123 2289-2296
    CrossrefPubMedGoogle Scholar
  • 42 Pinborg L H, Videbaek C, Hasselbalch S G, Sorensen S A, Wagner A, Paulson O B. et al . Benzodiazepine receptor quantification in Huntington's disease with [(123)I]omazenil and SPECT.  J Neurol Neurosurg Psychiatry. 2001;  70 657-661
    CrossrefPubMedGoogle Scholar
  • 43 Robertson H A, Martin I L, Candy J M. Differences in benzodiazepine receptor binding in Maudsley reactive and Maudsley non-reactive rats.  Eur J Pharmacol. 1978;  50 455-457
    CrossrefPubMedGoogle Scholar
  • 44 Drugan R C, Morrow A L, Weizman R, Weizman A, Deutsch S I, Crawley J N. et al . Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy.  Brain Res. 1989;  487 45-51
    CrossrefPubMedGoogle Scholar
  • 45 Drugan R C, Basile A S, Crawley J N, Paul S M, Skolnick P. Inescapable shock reduces [3H]Ro 5-4864 binding to “peripheral-type” benzodiazepine receptors in the rat.  Pharmacol Biochem Behav. 1986;  24 1673-1677
    CrossrefPubMedGoogle Scholar
  • 46 Weizman R, Weizman A, Kook K A, Vocci F, Deutsch S I, Paul S M. Repeated swim stress alters brain benzodiazepine receptors measured in vivo.  J Pharmacol Exp Ther. 1989;  249 701-707
    PubMedGoogle Scholar
  • 47 Weizman A, Bidder M, Fares F, Gavish M. Food deprivation modulates gamma-aminobutyric acid receptors and peripheral benzodiazepine binding sites in rats.  Brain Res. 1990;  535 96-100
    CrossrefPubMedGoogle Scholar
  • 48 Braestrup C, Schmiechen R, Neef G, Nielsen M, Petersen E N. Interaction of convulsive ligands with benzodiazepine receptors.  Science. 1982;  216 1241-1243
    PubMedGoogle Scholar
  • 49 Braestrup C, Nielsen M. Anxiety.  Lancet. 1982;  2 1030-1034
    PubMedGoogle Scholar
  • 50 Braestrup C, Nielsen M. beta-Carbolines and benzodiazepine receptors.  Prog Clin Biol Res. 1982;  90 227-231
    PubMedGoogle Scholar
  • 51 Ninan P T, Insel T M, Cohen R M, Cook J M, Skolnick P, Paul S M. Benzodiazepine receptor-mediated experimental “anxiety” in primates.  Science. 1982;  218 1332-1334
    PubMedGoogle Scholar
  • 52 Dorow R, Horowski R, Paschelke G, Amin M. Severe anxiety induced by FG 7142, a beta-carboline ligand for benzodiazepine receptors.  Lancet. 1983;  2 98-99
    PubMedGoogle Scholar
  • 53 Nutt D J, Glue P, Lawson C, Wilson S. Flumazenil provocation of panic attacks. Evidence for altered benzodiazepine receptor sensitivity in panic disorder.  Arch Gen Psychiatry. 1990;  47 917-925
    PubMedGoogle Scholar
  • 54 Woods S W, Charney D S, Silver J M, Krystal J H, Heninger G R. Behavioral, biochemical, and cardiovascular responses to the benzodiazepine receptor antagonist flumazenil in panic disorder.  Psychiatry Res. 1991;  36 115-127
    CrossrefPubMedGoogle Scholar
  • 55 Schlegel S, Steinert H, Bockisch A, Hahn K, Schloesser R, Benkert O. Decreased benzodiazepine receptor binding in panic disorder measured by IOMAZENIL-SPECT. A preliminary report.  Eur Arch Psychiatry Clin Neurosci. 1994;  244 49-51
    PubMedGoogle Scholar
  • 56 Kuikka J T, Pitkanen A, Lepola U, Partanen K, Vainio P, Bergstrom K A. et al . Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in patients with panic disorder.  Nucl Med Commun. 1995;  16 273-280
    PubMedGoogle Scholar
  • 57 Bremner J D, Innis R B, White T, Fujita M, Silbersweig D, Goddard A W. et al . SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder.  Biol Psychiatry. 2000;  47 96-106
    CrossrefPubMedGoogle Scholar
  • 58 Malizia A L, Cunningham V J, Bell C J, Liddle P F, Jones T, Nutt D J. Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study.  Arch Gen Psychiatry. 1998;  55 715-720
    PubMedGoogle Scholar
  • 59 Tiihonen J, Kuikka J, Rasanen P, Lepola U, Koponen H, Liuska A. et al . Cerebral benzodiazepine receptor binding and distribution in generalized anxiety disorder: a fractal analysis.  Mol Psychiatry. 1997;  2 463-471
    CrossrefPubMedGoogle Scholar
  • 60 Vythilingam M, Anderson E R, Goddard A, Woods S W, Staib L H, Charney D S. et al . Temporal lobe volume in panic disorder - a quantitative magnetic resonance imaging study.  Psychiatry Res. 2000;  99 75-82
    PubMedGoogle Scholar
  • 61 Fontaine R, Breton G, Dery R, Fontaine S, Elie R. Temporal lobe abnormalities in panic disorder: an MRI study.  Biol Psychiatry. 1990;  27 304-310
    CrossrefPubMedGoogle Scholar
  • 62 Spitzer R L, Williams J B, Skodol A E. DSM-III: the major achievements and an overview.  Am J Psychiatry. 1980;  137 151-164
    PubMedGoogle Scholar
  • 63 Gelpin E, Bonne O, Peri T, Brandes T, Shalev A. Treatment of recent trauma survivors with benzodiazepines: a prospective study.  J Clin Psychiatry. 1996;  57 390-394
    PubMedGoogle Scholar
  • 64 Bremner J D. Neuroimaging of childhood trauma.  Semin Clin Neuropsychiatry. 2002;  7 104-112
    CrossrefPubMedGoogle Scholar
  • 65 Bonne O, Brandes D, Gilboa A, Gomori J M, Shenton M E, Pitman R K. et al . Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD.  Am J Psychiatry. 2001;  158 1248-1251
    CrossrefPubMedGoogle Scholar
  • 66 Carrion V G, Weems C F, Eliez S, Patwardhan A, Brown W, Ray R D. et al . Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder.  Biol Psychiatry. 2001;  50 943-951
    CrossrefPubMedGoogle Scholar
  • 67 Bremner J D, Innis R B, Southwick S M, Staib L, Zoghbi S, Charney D S. Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder.  Am J Psychiatry. 2000;  157 1120-1126
    CrossrefPubMedGoogle Scholar
  • 68 Skerritt J H, Johnston G A, Braestrup C. Modulation of GABA binding to rat brain membranes by alkyl beta-carboline-3-carboxylate esters.  Eur J Pharmacol. 1982;  86 299-301
    CrossrefPubMedGoogle Scholar
  • 69 Pauli S, Liljequist S, Farde L, Swahn C G, Halldin C, Litton J E. et al . PET analysis of alcohol interaction with the brain disposition of [11C]flumazenil.  Psychopharmacology (Berl). 1992;  107 180-185
    PubMedGoogle Scholar
  • 70 Robertson C C, Sellers E M. Alcohol intoxication and the alcohol withdrawal syndrome.  Postgrad Med. 1978;  64 133-138
    PubMedGoogle Scholar
  • 71 Hemmingsen R, Braestrup C, Nielsen M, Barry D I. The benzodiazepine/GABA receptor complex during severe ethanol intoxication and withdrawal in the rat.  Acta Psychiatr Scand. 1982;  65 120-126
    PubMedGoogle Scholar
  • 72 Potokar J, Coupland N, Glue P, Groves S, Malizia A, Bailey J. et al . Flumazenil in alcohol withdrawal: a double-blind placebo-controlled study.  Alcohol Alcohol. 1997;  32 605-611
    PubMedGoogle Scholar
  • 73 Freund G, Ballinger W E. Loss of muscarinic and benzodiazepine neuroreceptors from hippocampus of alcohol abusers.  Alcohol. 1989;  6 23-31
    CrossrefPubMedGoogle Scholar
  • 74 Freund G, Ballinger W E. Decrease of benzodiazepine receptors in frontal cortex of alcoholics.  Alcohol. 1988;  5 275-282
    CrossrefPubMedGoogle Scholar
  • 75 Korpi E R, Uusi-Oukari M, Wegelius K, Casanova M, Zito M, Kleinman J E. Cerebellar and frontal cortical benzodiazepine receptors in human alcoholics and chronically alcohol-drinking rats.  Biol Psychiatry. 1992;  31 774-786
    CrossrefPubMedGoogle Scholar
  • 76 Litton J E, Neiman J, Pauli S, Farde L, Hindmarsh T, Halldin C. et al . PET analysis of [11C]flumazenil binding to benzodiazepine receptors in chronic alcohol-dependent men and healthy controls.  Psychiatry Res. 1993;  50 1-13
    CrossrefPubMedGoogle Scholar
  • 77 Farde L, Pauli S, Litton J E, Halldin C, Neiman J, Sedvall G. PET-determination of benzodiazepine receptor binding in studies on alcoholism.  Exs. 1994;  71 143-153
    PubMedGoogle Scholar
  • 78 Nutt D, Glue P, Wilson S, Groves S, Coupland N, Bailey J. Flumazenil in alcohol withdrawal.  Alcohol Alcohol Suppl. 1993;  2 337-341
    PubMedGoogle Scholar
  • 79 Gilman S, Adams K M, Johnson-Greene D, Koeppe R A, Junck L, Kluin K J. et al . Effects of disulfiram on positron emission tomography and neuropsychological studies in severe chronic alcoholism.  Alcohol Clin Exp Res. 1996;  20 1456-1461
    PubMedGoogle Scholar
  • 80 Abi-Dargham A, Krystal J H, Anjilvel S, Scanley B E, Zoghbi S, Baldwin R M. et al . Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil.  Am J Psychiatry. 1998;  155 1550-1555
    PubMedGoogle Scholar
  • 81 Lingford-Hughes A R, Acton P D, Gacinovic S, Suckling J, Busatto G F, Boddington S J. et al . Reduced levels of GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy.  Br J Psychiatry. 1998;  173 116-122
    PubMedGoogle Scholar
  • 82 Lingford-Hughes A R, Acton P D, Gacinovic S, Boddington S J, Costa D C, Pilowsky L S. et al . Levels of gamma-aminobutyric acid-benzodiazepine receptors in abstinent, alcohol-dependent women: preliminary findings from an 123I-iomazenil single photon emission tomography study.  Alcohol Clin Exp Res. 2000;  24 1449-1455
    PubMedGoogle Scholar
  • 83 Greenfield S F. Women and alcohol use disorders.  Harv Rev Psychiatry. 2002;  10 76-85
    PubMedGoogle Scholar
  • 84 Wang G J, Volkow N D, Fowler J S, Pappas N R, Wong C T, Pascani K. et al . Regional cerebral metabolism in female alcoholics of moderate severity does not differ from that of controls.  Alcohol Clin Exp Res. 1998;  22 1850-1854
    PubMedGoogle Scholar
  • 85 Garbutt J C, van-Kammen D P. The interaction between GABA and dopamine: implications for schizophrenia.  Schizophr Bull. 1983;  9 336-353
    PubMedGoogle Scholar
  • 86 Stevens J, Wilson K, Foote W. GABA blockade, dopamine and schizophrenia: experimental studies in the cat.  Psychopharmacologia. 1974;  39 105-119
    PubMedGoogle Scholar
  • 87 Squires R F, Saederup E. Indomethacin/ibuprofen-like anti-inflammatory agents selectively potentiate the gamma-aminobutyric acid-antagonistic effects of several norfloxacin-like quinolone antibacterial agents on [35S]t-butylbicyclophosphorothionate binding.  Mol Pharmacol. 1993;  43 795-800
    PubMedGoogle Scholar
  • 88 Simpson M D, Slater P, Deakin J F, Royston M C, Skan W J. Reduced GABA uptake sites in the temporal lobe in schizophrenia.  Neurosci Lett. 1989;  107 211-215
    CrossrefPubMedGoogle Scholar
  • 89 Reynolds G P, Czudek C, Andrews H B. Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia.  Biol Psychiatry. 1990;  27 1038-1044
    CrossrefPubMedGoogle Scholar
  • 90 Busatto G F, Pilowsky L S, Costa D C, Ell P J, David A S, Lucey J V et al. Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia.  Am J Psychiatry. 1997;  154 56-63
    PubMedGoogle Scholar
  • 91 Ball S, Busatto G F, David A S, Jones S H, Hemsley D R, Pilowsky L S. et al . Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study.  Biol Psychiatry. 1998;  43 107-117
    CrossrefPubMedGoogle Scholar
  • 92 Verhoeff N P, Soares J C, D'Souza C D, Gil R, Degen K, Abi-Dargham A. et al . [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia.  Psychiatry Res. 1999;  91 163-173
    PubMedGoogle Scholar
  • 93 Abi-Dargham A, Laruelle M, Krystal J, D≈ os;Souza C, Zoghbi S, Baldwin R M. et al . No evidence of altered in vivo benzodiazepine receptor binding in schizophrenia.  Neuropsychopharmacology. 1999;  20 650-661
    CrossrefPubMedGoogle Scholar
  • 94 Soares J C, Innis R B. Neurochemical brain imaging investigations of schizophrenia.  Biol Psychiatry. 1999;  46 600-615
    CrossrefPubMedGoogle Scholar
  • 95 Moeller H J, Kissling W, Wendt G. Psychopharmakotherapie. Ein Leitfaden für Klinik und Praxis.  Stuttgart: Kohlhammer-Verlag; 1989..
    PubMedGoogle Scholar

Dr. F. D. Juengling

Abteilung für Nuklearmedizin, Radiologie III

Universitätsklinik Ulm

Robert Koch-Str. 8

89075 Ulm

Phone: +49/7 31/50 02 45 06

Fax: +49/7 31/50 02 45 12

Email: freimut.juengling@medizin.uni-ulm.de

      >