Schizophrenia and Psychotic Disorder

  • James Stone
  • Lyn S. Pilowsky


It is clear that SPET and PET scanning methods have been of key importance in furthering the understanding of the pathophysiology of schizophrenia. The unique ability to image receptor flux in living subjects is vital to understanding this condition, in which the locus of disease is likely to be at the molecular, or neurotransmitter level. Work so far has concentrated mainly on the involvement of dopamine in schizophrenia, but this is not likely to be the whole story. As new ligands are developed, further insights will be gained in the underlying pathology in schizophrenia. New techniques combining functional imaging with genetic studies are likely to be of increasing importance in the coming years, and interest in neural plasticity will mean that future work will not simply be static analysis of receptor populations but will concentrate more on long-term dynamic changes induced by the illness and its treatments.


Positron Emission Tomography Dopamine Receptor Atypical Antipsychotic Positron Emission Tomography Study Receptor Occupancy 
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  1. Abi-Dargham A, Kegeles L, Zea-Ponce Y, Printz D, Gil R, Rodenhiser J, Gorman J, Mann J, Van Heertum R, Lamelle M (1999) Imaging resting phasic dopamine synaptic activity in schizophrenia. Schizophr Res 36:239CrossRefGoogle Scholar
  2. 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 22:3708–3719PubMedGoogle Scholar
  3. 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. [123I]epidepride single photon emission tomography (SPET) study. Br J Psychiatry 175:231–238PubMedCrossRefGoogle Scholar
  4. 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 and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study. Psychopharmacology (Berl) 150:132–140CrossRefGoogle Scholar
  5. Bressan RA, Pilowsky LS (2000) Imaging the glutamatergic system in vivo — relevance to schizophrenia. Eur J Nucl Med 27:1723–1731PubMedCrossRefGoogle Scholar
  6. Bressan RA, Erlandsson K, Jones HM, Mulligan RS, Ell PJ, Pilowsky LS (2003) Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a [123I]-epidepride SPET study. J Clin Psychopharmacol 23:5–14PubMedCrossRefGoogle Scholar
  7. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483PubMedCrossRefGoogle Scholar
  8. Farde L, Wiesel FA, Halldin C, Sedvall G (1988) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45:71–76PubMedCrossRefGoogle Scholar
  9. Farde L, Wiesel FA, Stone-Elander S, Halldin C, Nordstrom AL, Hall H, Sedvall G (1990) D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry 47:213–219PubMedCrossRefGoogle Scholar
  10. Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G (1992) Positron emission tomographic 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 49:538–544PubMedCrossRefGoogle Scholar
  11. 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) 135:119–126CrossRefGoogle Scholar
  12. Johnstone EC, Crow TJ, Frith CD, Carney MW, Price JS (1978) Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet 1:848–851PubMedCrossRefGoogle Scholar
  13. 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 159:761–767PubMedCrossRefGoogle Scholar
  14. Kapur S, Seeman P (2001) Does fast dissociation from the dopamine D(2) receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 158:360–369PubMedCrossRefGoogle Scholar
  15. Kapur S, Zipursky RB, Remington G (1999) Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 156:286–293PubMedGoogle Scholar
  16. Kapur S, Zipursky R, Jones C, Remington G, Houle S (2000a) Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 157:514–520PubMedCrossRefGoogle Scholar
  17. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P (2000b) A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry 57:553–559PubMedCrossRefGoogle Scholar
  18. 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. Schizophr Res 60:242CrossRefGoogle Scholar
  19. Lamelle 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 Sei U S A 93:9235–9240CrossRefGoogle Scholar
  20. 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 156:72–78PubMedGoogle Scholar
  21. Lidow MS, Goldman-Rakic PS (1997) Differential regulation of D2 and D4 dopamine receptor mRNAs in the primate cerebral cortex vs. neostriatum: effects of chronic treatment with typical and atypical antipsychotic drugs. J Pharmacol Exp Ther 283:939–946Google Scholar
  22. Mackay AVP, Bird ED, Spokes EG (1980) Dopamine receptors and schizophrenia: drug effect or illness? Lancet 2:915–916PubMedCrossRefGoogle Scholar
  23. Martinot JL, Paillere-Martinot ML, Loc’h C, Hardy P, Poirier MF, Mazoyer B, Beaufils B, Maziere B, Allilaire JF, Syrota A (1991) The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br J Psychiatry 158:346–350PubMedCrossRefGoogle Scholar
  24. Meltzer HY, Matsubara S (1989) The ratios of serotonin and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull 25:390–397PubMedGoogle Scholar
  25. Moore H, West AR, Grace AA (1999) The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia. Biol Psychiatry 46:40–55PubMedCrossRefGoogle Scholar
  26. Morisette M, Goulet M, Grondin R, Blanchet P, Bedard PJ, Di Paolo T, Levesque D (1998) Associative and limbic regions of monkey striatum express high levels of dopamine D3 receptors: effects of MPTP and dopamine agonist replacement therapies. Eur J Neurosci 10:2565–2573CrossRefGoogle Scholar
  27. Ngan ET, Yatham LN, Ruth TJ, Liddle PF (2000) Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: A PET study using [(18)F]setoperone. Am J Psychiatry 157:1016–1018PubMedCrossRefGoogle Scholar
  28. Nordstrom AL, Farde L, Wiesel FA, Forslund K, Pauli S, Halldin C, Uppfeldt G (1993a) Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiatry 33:227–235PubMedCrossRefGoogle Scholar
  29. Nordstrom AL, Farde L, Halldin C (1993b) High 5HT2 receptor occupancy in clozapine treated patients demonstrated by PET. Psychopharmacology 110:365–367PubMedCrossRefGoogle Scholar
  30. Nyberg S, Farde L, Eriksson L, Halldin C, Eriksson B (1993) 5HT2 and D2 dopamine receptor occupancy in the living human brain of risperidone. Psychopharmacology 110:265–272PubMedCrossRefGoogle Scholar
  31. Okubo Y, Suhara T, Sudo Y, Toru M (1997) Possible role of dopamine D1 receptors in schizophrenia. Mol Psychiatry 2:291–292CrossRefGoogle Scholar
  32. Owen F, Crow TJ, Poulter M (1978) Increased dopamine receptor sensitivity in schizophrenia. Lancet 2:223–225PubMedCrossRefGoogle Scholar
  33. Peroutka SJ, Synder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic, and histamine receptors to clinical potency. Am J Psychiatry 137: 1518–1522PubMedGoogle Scholar
  34. Pilowsky LS, Costa DC, Ell PJ, Murray RM, Verhoeff NP, Kerwin RW (1992) Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 340:199–202PubMedCrossRefGoogle Scholar
  35. Pilowsky LS, Costa DC, Ell PJ, Murray RM, Verhoeff NP, Kerwin RW (1993) Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study. Psychol Med 23:791–797PubMedCrossRefGoogle Scholar
  36. Pilowsky LS, Costa DC, Ell PJ, Verhoeff NP, Murray RM, Kerwin RW (1994) D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An 123I-IBZM single photon emission computerised tomography study. Br J Psychiatry 164:16–26PubMedCrossRefGoogle Scholar
  37. Pilowsky LS, Mulligan RS, Acton PD, Ell PJ, Costa DC, Kerwin RW (1997) Limbic selectivity of clozapine. Lancet 350:490–491CrossRefGoogle Scholar
  38. Plum F (1972) Prospects for research on schizophrenia. 3. Neurophysiology. Neuropathological findings. Neurosci Res Progr Bull 10:384–388Google Scholar
  39. Seeman P, Ulpian C, Bergeron C, Riederer P, Jellinger K, Gabriel E, Reynolds GP, Tourtellotte WW (1984) Bimodal distribution of dopamine receptor densities in brains of schizophrenics. Science 225:728–731PubMedCrossRefGoogle Scholar
  40. Stephenson CM, Bigliani V, Jones HM, Mulligan RS, Acton PD, Visvikis D, Ell PJ, Kerwin RW, Pilowsky LS (2000) Striatal and extra-striatal D(2)/D(3) dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography (SPET) study. Br J Psychiatry 177:408–415PubMedCrossRefGoogle Scholar
  41. Stone JM, Bressan RA, Erlandsson K, Davies G, Ell PJ, Pilowsky LS (2003) Intrastriatal selectivity of atypical antipsychotics: a voxel based analysis. J Psychopharmacol 17[Suppl 3]:A49Google Scholar
  42. Strange PG (2001) Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev 53:119–133PubMedGoogle Scholar
  43. 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) receptor binding in schizophrenia measured by positron emission tomography and [11C] WAY-100635. Arch Gen Psychiatry 59:514–520PubMedCrossRefGoogle Scholar
  44. Travis MJ, Busatto GF, Pilowsky LS et al (1997) Serotonin 5-HT2a occupancy in vivo and response to the new antipsychotics olanzapine and sertindole (letter). Br J Psychiat 171:290–291CrossRefGoogle Scholar
  45. 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 155:505–508PubMedGoogle Scholar
  46. 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 7:233,322–328CrossRefGoogle Scholar
  47. Wolkin A, Barouche F, Wolf AP, Rotrosen J, Fowler JS, Shiue CY, Cooper TB, Brodie JD (1989) Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. Am J Psychiatry 146:905–908PubMedGoogle Scholar
  48. Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA et al (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naïve schizophrenics. Science 234:1558–1563PubMedCrossRefGoogle Scholar
  49. Xiberas X, Martinot JL, Mallet L, Artiges E, Canal M, Loc’h C, Maziere B, Paillere-Martinot ML (2001) In vivo extrastriatal and striatal D2 dopamine receptor blockade by amisulpride in schizophrenia. J Clin Psychopharmacol 21:207–214PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • James Stone
    • 1
  • Lyn S. Pilowsky
    • 1
  1. 1.Institute of PsychiatryDenmark Hill, LondonUK

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