Skip to main content
SpringerLink
Log in

What can molecular imaging tell us about schizophrenia?

  • Conference paper
Search for the Causes of Schizophrenia

  • 303 Accesses

Abstract

The term molecular imaging refers in this review to a type of nuclear medicine procedure in which a molecule of interest is labelled with an isotope (positron or single photon emitting nuclide), and acts as a molecular ‘key’ (or radioligand), fitting into a cellular recognition site (receptor, transporter protein or enzymatic pathway) with molecular-level specificity. The radioligand is injected into the bloodstream, passes through the blood brain barrier and binds to a site of interest. When bound, the emitted radiation is detected by a ring of detectors surrounding the head, and a map of radioactive density is produced, reflecting a chemical map of radioligand binding. Thus neurotransmitter systems in the living human brain may be studied relatively noninvasively.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abi-Dargham A, Kegeles L, Zea-Ponce Y, Printz D, Gil R, Rodenhiser J, Gorman J, Mann J, Van Heertum R, Laruelle M (1999) Imaging resting phasic dopamine synaptic activity in schizophrenia, Schizophrenia Research 36:239

    Article  Google Scholar 

  • Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 97(14):8104–8109

    Article  PubMed  CAS  Google Scholar 

  • Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y, Hwang DR, Keilp J, Kochan L, Van Heertum R, Gorman JM, Laruelle M (2002) Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 22(9): 3708–3719

    PubMed  CAS  Google Scholar 

  • Bigliani V, Mulligan RS, Acton PD, Visvikis D, Ell PJ, Stephenson C, Kerwin RW, Pilowsky LS (1999) In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs - a [123I] epidepride single photon emission tomography (SPET) study, Brit J Psychiatry 175:231–238

    Article  CAS  Google Scholar 

  • Bigliani V, Mulligan RS, Acton PD, Ohlsen RI, Pike VW, Ell PJ, Gacinovic S, Kerwin RW, Pilowsky LS (2000) Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine - a123I epidepride single photon emission tomography (SPET) study. Psychopharmacology 150:132–140

    Article  PubMed  CAS  Google Scholar 

  • Bressan RA, Erlandsson K, Mulligan RS, Gunn RN, Cunningham VJ, Owens J, Ell PJ, Pilowsky LS (2003) Evaluation of NMDA receptors in vivo in schizophrenic patients with [123I] CNS 1261 and SPET; proceedings: glutamate and disorders of cognition and motivation. New York Acad Sciences Conference, April 2003, 8

    Google Scholar 

  • Carlsson A (2001) A half-century of neurotransmitter research: impact on neurology and psychiatry. Nobel lecture. Biosci Rep 21(6):691–710

    Article  CAS  Google Scholar 

  • Connell P (1958) Amphetamine Psychosis. Maudsley Monograph No 5. Oxford University Press, London (pubs)

    Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483

    Article  PubMed  CAS  Google Scholar 

  • Crow TJ (1980) Molecular pathology of schizophrenia: more than one disease pro-cess? BMJ 280:66–68

    Article  PubMed  CAS  Google Scholar 

  • Farde L, Wiesel F-A, Stone-Elander S et al (1990) D2 dopamine receptors in neuro-leptic naive schizophrenic patients. Archives of General Psychiatry 47:213–219

    Article  PubMed  CAS  Google Scholar 

  • Farde L, Pauli S, Hall H et al (1988) Stereoselective binding of 11C raclopride in the living human brain - a search for extrastriatal central D2 receptors by PET. Psychopharmacology 94:471–478

    Article  PubMed  CAS  Google Scholar 

  • Farde L, Nordstrom AL, Wiesel F-A et al (1992) Positron emission tomographic analysis of central D1 and D2 receptor occupancy in patients treated with classical neuroleptics and clozapine. Archives of General Psychiatry 49:538–544

    Article  PubMed  CAS  Google Scholar 

  • Farde L, Nordstrom AL, Wiesel A, Pauli S, Halldin C, Sedvall G (1992) Positron emission tomography analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side-effects. Arch Gen Psychiatry 49:538–543

    Article  PubMed  CAS  Google Scholar 

  • Gefvert O, Bergstrom M, Langstrom B, Lundberg T, Lindstrom L, Yates R (1998) Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel) in patients with schizophrenia. Psychopharmacology (Berl) 135(2):119–126

    Article  CAS  Google Scholar 

  • Johnstone EC, Crow TJ, Frith CD, Carney MWP, Price JS (1978) Mechanisms of the antipsychotic effect in the treatment of acute schizophrenia. Lancet i:848–851

    Google Scholar 

  • Kapur S, Zipursky R, Jones C, Remington G, Houle S (2000) Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157(4):514–520

    Article  PubMed  CAS  Google Scholar 

  • Kapur S, Zipursky R, Remington G (1999) Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 156(2):286–293

    PubMed  CAS  Google Scholar 

  • Kapur S, Seeman P (2001) Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics? A new hypothesis. American Journal of Psychiatry 158:360–369

    Article  PubMed  CAS  Google Scholar 

  • Karlsson P, Farde L, Halldin C, Sedvall G (2002) PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with schizophrenia. Am J Psychiatry 159(5):761–767

    Article  PubMed  Google Scholar 

  • Kessler RM, Whetsell WO, Sib Ansari M, Votaw JR, Paulis T de, Clanton JA, Schmidt DE, Scott Mason N, Manning RG (1993) Identification of extrastriatal dopamine D2 receptors in post mortem human brain with 1251-epidepride. Brain Research 609:237–243

    Article  PubMed  CAS  Google Scholar 

  • Kessler RM, Ansari MS, Lui R, Dawant B, Meltzer HY (2003) Occupancy of cortical and substantia nigra DA D2 receptors by typical and atypical antipsychotic drugs. Schizophrenia Research 60(1):242

    Article  Google Scholar 

  • Laruelle M, Abi-Dargham A, Van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 93/17:9235–9240

    Article  Google Scholar 

  • Lewis R, Kapur S, Jones C, DaSilva J, Brown GM, Wilson AA, Houle S, Zipursky RB (1999) Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F] setoperone in neuroleptic-naive patients and normal subjects. Am J Psychiatry 156(1): 72–78

    PubMed  CAS  Google Scholar 

  • Lidow MS, Williams GV, Goldman-Rakic PS (1998) The cerebral cortex: a case for a common site of action of antipsychotics. Trends Pharmacol Sci 19(4):136–140

    Article  PubMed  CAS  Google Scholar 

  • Martinot J-L, Palliere-Martinot ML, Loc’h C et al (1991)The estimated density of D2 striatal receptors in schizophrenia - a study with positron emission tomography and 76Br-bromolisuride. 158:346–350

    CAS  Google Scholar 

  • Meltzer HY, Matsubara S (1989) The ratios of serotonin and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacology Bulletin 25:390–397

    PubMed  CAS  Google Scholar 

  • Moore H, West AR, Grace AA (1999) The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia. Biol Psychiatry 46(1):40–55

    Article  PubMed  CAS  Google Scholar 

  • Ngan ET, Yatham LN, Ruth TJ, Liddle PF (2000) Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: a PET study using [18F] setoperone. Am J Psychiatry 157(6):1016–1018

    Article  PubMed  CAS  Google Scholar 

  • Nordstrom AL, Farde L, Weisel FA, Forslund K, Pauli S, Halldin C, Uppfeldt G (1993) Central D2 dopamine receptor occupancy in relation to antipsychotic drug effects: a double blind PET study of schizophrenic patients. Biol Psychiatry 33:227–235

    Article  PubMed  CAS  Google Scholar 

  • Nyberg S, Farde L, Eriksson L, Halldin C, Eriksson B (1993) 5HT2 and D2 dopamine receptor occupancy by risperidone in the living human brain. Psychopharmacology 110:265–272

    Article  PubMed  CAS  Google Scholar 

  • Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M (1997) Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385(6617):634–636

    Article  PubMed  CAS  Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic and histaminergic receptors to clinical potency. Am J Psychiatry 137:1518–1522

    PubMed  CAS  Google Scholar 

  • Pilowsky LS, Costa DC, Ell PJ, Verhoeff NPLG, Murray RM, Kerwin RW (1994) D2 dopamine receptor binding in the basal ganglia of antipsychotic free schizophrenic patients - a123I IBZM single photon emission tomography (SPET) study. British Journal of Psychiatry 164:16–26

    Article  PubMed  CAS  Google Scholar 

  • Pilowsky LS, Costa DC, Ell PJ, Murray R, Verhoeff N, Kerwin RW (1993) Antipsychotic medication, D2 dopamine receptor blockade and clinical response - a123I IBZM SPET (single photon emission tomography) study. Psychol Med 23:791–799

    Article  PubMed  CAS  Google Scholar 

  • Pilowsky LS, Costa DC, Ell PJ, Murray R, Verhoeff N, Kerwin RW (1992) Clozapine, single photon emission tomography and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 340:199–202

    Article  PubMed  CAS  Google Scholar 

  • Pilowsky LS, Mulligan RS, Acton PD, Costa DC, Ell PJ, Kerwin RW (1997) Limbic selectivity of clozapine. The Lancet 350:490–491

    Article  CAS  Google Scholar 

  • Raedler TJ, Knable MB, Jones DW, Urbina RA, Gorey JG, Lee KS, Egan MF, Coppola R, Weinberger DR (2003) In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry 160(1):118–127

    Article  PubMed  Google Scholar 

  • Seeman P (2002) Atypical antipsychotics: mechanism of action. Can J Psychiatry 47: 27–38

    PubMed  Google Scholar 

  • Stephenson C, Bigliani V, Kerwin W, Mulligan RS, Acton PD, Pike VW, Ell PJ, Gacinovic S, Pilowsky LS (2000) The action of quetiapine at striatal and extra-striatal D2/D3 receptors in vivo. Brit J Psychiatry 177:408–415

    Article  CAS  Google Scholar 

  • Strange PG (2001) Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacological Reviews 53:119–133

    PubMed  CAS  Google Scholar 

  • Tauscher J, Kapur S, Verhoeff NP, Hussey DF, Daskalakis ZJ, Tauscher-Wisniewski S, Wilson AA, Houle S, Kasper S, Zipursky RB (2002) Brain serotonin 5-HT(1A) re-ceptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. Arch Gen Psychiatry 59(6):514–520

    Article  PubMed  CAS  Google Scholar 

  • Travis MJ, Busatto GF, Pilowsky LS, Kerwin RW, Mulligan RS, Gacinovic S, Costa DCC, Ell PJ, Mertens J, Terriere D (1997) Serotonin 5-HT2a occupancy in vivo and response to the new antipsychotics olanzapine and sertindole. Brit J Psychiat (Let) 171:290–291

    Article  CAS  Google Scholar 

  • Travis MJ, Busatto GF, Pilowsky LS, Mulligan R, Acton PD et al (1998) 5HT2a receptor blockade in schizophrenic patients treated with risperidone or clozapine, a123I-5-I-R-91150 single photon emission tomography (SPET) study. Brit J Psychiatry 173:236–242

    Article  CAS  Google Scholar 

  • Trichard C, Paillere-Martinot ML, Attar-Levy D, Recassens C, Monnet F, Martinot JL (1998) Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients., Am J Psychiatry 155(4):505–508

    PubMed  CAS  Google Scholar 

  • Wolkin A, Barouche F, Wolf AP, Rotrosen J, Fowler JS, Shiue C-Y, Cooper TB, Brodie JD (1989) Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. American Journal of Psychiatry 146:905–908

    PubMed  CAS  Google Scholar 

  • Wong DF, Wagner Jr HN, Tune LE et al (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558–1563

    Article  PubMed  CAS  Google Scholar 

  • Verhoeff NP, Hussey D, Lee M, Tauscher J, Papatheodorou G, Wilson AA, Houle S, Kapur S (2002) Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans. Mol Psychiatry 7(3):233, 322–328

    Article  PubMed  CAS  Google Scholar 

  • Xiberas X, Martinot JL, Mallet L, Artiges E, Loc’h C, Maziere B, Pailliere-Martinot M (2001) Extrastriatal and striatal D2 dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. British Journal of Psychiatry 179:503–509

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Reader in Neurochemical Imaging, UK Medical Research Council Senior Clinical Fellow, Institute of Psychiatry, London, UK

    Lyn S. Pilowsky

Authors
  1. Lyn S. Pilowsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department and Institute of Psychiatry - Faculty of Medicine, University of São Paulo, 3671, 05403-010, São Paulo - SP, Brazil

    Wagner F. Gattaz M.D. (Full Professor of Psychiatry & Director of the Laboratory of Neuroscience) (Full Professor of Psychiatry & Director of the Laboratory of Neuroscience)

  2. University of Heidelberg, 122120, 68072, Mannheim, Germany

    Heinz Häfner (Prof.em.of Psychiatry, Director em., Head) (Prof.em.of Psychiatry, Director em., Head)

  3. Central Institute of Mental Health, 122120, 68072, Mannheim, Germany

    Heinz Häfner (Prof.em.of Psychiatry, Director em., Head) (Prof.em.of Psychiatry, Director em., Head)

  4. Schizophrenia Research Unit, 122120, 68072, Mannheim, Germany

    Heinz Häfner (Prof.em.of Psychiatry, Director em., Head) (Prof.em.of Psychiatry, Director em., Head)

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Pilowsky, L.S. (2004). What can molecular imaging tell us about schizophrenia?. In: Gattaz, W.F., Häfner, H. (eds) Search for the Causes of Schizophrenia. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-7985-1953-4_29

Download citation

  • DOI: https://doi.org/10.1007/978-3-7985-1953-4_29

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-642-62331-8

  • Online ISBN: 978-3-7985-1953-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation