Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-22T07:53:46.396Z Has data issue: false hasContentIssue false

In vivo neuropharmacology of schizophrenia

Published online by Cambridge University Press:  06 August 2018

V. Bigliani
Affiliation:
Institute of Psychiatry, London
L. S. Pilowsky*
Affiliation:
Institute of Psychiatry, London
*
Correspondence: L. Pilowsky, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SES 8AF

Extract

Since the introduction of chlorpromazine in the 1950s, followed by the discovery (with in vitro receptor binding assays), in the mid-1970s, that antipsychotic drugs block a subtype of dopamine receptor (D2/D2-like) (Creese et al, 1976) and that affinity for these receptors appears to correlate directly with clinical potency for antipsychotics (Peroutka & Synder, 1980), the study of neurotransmitters and receptors has been a major target of schizophrenia research (Owens, 1996). In 1983, the first visualisation, by positron emission tomography (PET), of the binding of D2 dopamine receptors in the brain of a living human subject was reported (Wagner et al, 1983). Following this, the number of research studies using PET and single photon emission tomography (SPET) has increased enormously.

Type
Research Article
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Acton, P., Pilowsky, L., Costa, D. & Ell, P. (1997) Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2 receptor images in schizophrenia. European Journal of Nuclear Medicine, 24, 111118.CrossRefGoogle ScholarPubMed
Andreasen, N., Carson, R., Diksic, M., et al (1988) Workshop in schizophrenia, PET, and dopamine D2 receptors in the human neostriatum. Schizophrenia Bulletin, 14, 471484.CrossRefGoogle ScholarPubMed
Antonini, A. & Leenders, K. L. (1993) Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and “C-raclopride. Annals of the New York Academy of Sciences, 695, 8185.CrossRefGoogle Scholar
Bailey, D. L. & Parker, J. A. (1994) Single Photon Emission Computerized Tomography. In Nuclear Medicine in Clinical Diagnosis and Treatment (eds Murray, I. P. C. & Ell, P.J.), vol. 2, pp. 13151325. Edinburgh: Churchill Livingstone.Google Scholar
Bailey, D. L., Zito, F., Guardi, M. C., et al (1994b) Performance comparison of state-of-art neuro-SPET scanner and a dedicated neuro-PET scanner. European Journal of Nuclear Medicine, 21, 381387.CrossRefGoogle Scholar
Bench, R., Dolan, C. & Fristen, C. (1990) Positron emission tomography in psychopharmacology. International Review of Psychiatry, 2, 427439.Google Scholar
Bigliani, V., Mulligan, R. S., Acton, P. D., et al (1998a) Different patterns of D2/D2-like blockade in the temporal cortex and striatum by typical antipsychotics: an 1231 epidepride SPET study. Schizophrenia Research, 29, 169.CrossRefGoogle Scholar
Bigliani, V., Mulligan, R. S., Acton, P. D., et al (1998b) Preliminary results: D2/D2-like receptor binding in temporal cortex and striatum in sertindole and olanzapine treated patients. Journal of Nuclear Medicine, 39, 319.Google Scholar
Brier, A., Su, T.-P., Saunders, R., et al (1997) Assessment of synaptic dopamine concentrations in schizophrenia with PET (abstract, VI International Congress on Schizophrenia Research, Colorado Springs, April 12–16, 1997). Schizophrenia Research, 24, 176.CrossRefGoogle Scholar
Busatto, G. F. & Pilowsky, L. S. (1995) Neuroreceptor imaging with PET and SPET: research and clinical application in neurobiology and psychiatry. In Cambridge Medical Reviews Vol. 3 Neuroimaging (ed. Kerwin, R.). Cambridge: Cambridge University Press.Google Scholar
Busatto, G., Pilowsky, L., Costa, D., et al (1995a) In vivo imaging of GABA-A receptors using sequential whole-volume iodine-123 iomazenil single photon emission tomography. European Journal of Nuclear Medicine, 22, 1216.CrossRefGoogle ScholarPubMed
Busatto, G., Pilowsky, L., Costa, D., et al (1995b) Dopamine D2 receptor blockade in vivo with the novel antipsychotics risperidone and remoxipride- an 12311-IBZM single photo emission tomography (SPET) study. Psychopharmacology, 117, 5561.CrossRefGoogle Scholar
Busatto, G. & Kerwin, R. (1997a) Perspectives on the role of serotonergic mechanisms in the pharmacology of schizophrenia. Journal of Psychopharmacology, 11, 312.CrossRefGoogle ScholarPubMed
Busatto, G., Pilowsky, L., Costa, D., et al (1997b) Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia. American Journal of Psychiatry, 154, 5663.Google ScholarPubMed
Busatto, G., Pilowsky, L., Costa, D., et al (1997c) Initial evaluation of 1231-5-1-R91150, a selective 5HT2a ligand for single photon emission tomography (SPET), in healthy human subjects. European Journal of Nuclear Medicine, 22, 1217.CrossRefGoogle Scholar
Creese, I., Burt, D. R. & Snyder, S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481483.CrossRefGoogle ScholarPubMed
Crow, T. J. (1980) Molecular pathology of schizophrenia: more than one disease process? British Medical Journal, 66–68.Google Scholar
Davis, K., Kahn, R., Ko, G., et al (1991) Dopamine in schizophrenia: a review and reconceptualization. American Journal of Psychiatry, 148, 14741484.Google ScholarPubMed
Deutsch, A. Y., Moghaddam, B., Innis, R. B., et al (1991) Mechanism of action of atypical antipsychotic drugs. Implication for novel therapeutic strategies for schizophrenia. Schizophrenia Research, 4, 121156.CrossRefGoogle Scholar
Dolan, R. J., Bench, C. J., Liddle, P. F., et al (1993) Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptoms or disease specificity? Journal of Neurology, Neurosurgery and Psychiatry, 56, 12901294.CrossRefGoogle ScholarPubMed
Eberl, S. & Zimmerman, (1994) Nuclear medicine imaging instrumentation. In Nuclear Medicine in Clinical Diagnosis and Treatment (eds Murray, I. P. C. & Ell, P. J.), vol. 2, pp. 12911298. Edinburgh: Churchill Livingstone.Google Scholar
Farde, L., Hall, H., Ehrin, E. & Sedval, I., (1986) Quantitative analysis of D2 dopamine receptor binding in the living human by PET. Science, 231, 258261.CrossRefGoogle ScholarPubMed
Farde, L., Halldin, C., Stone-Elander, S. & Sedvall, G. (1987a) PET analysis of human dopamine receptor subtypes using “C-SCH23390 and “C-raclopride. Psychopharmacology (Berlin), 92, 278284.CrossRefGoogle Scholar
Farde, L., Wiesel, F., Hall, H., et al (1987b) No D2 receptor increase in PET study of schizophrenia (letter). Archives of General Psychiatry, 44, 671672.CrossRefGoogle Scholar
Farde, L., Pauli, S., Hall, H., et al (1988) Stereoselective binding of 11C-raclopnde in living human brain – a search for extrastriatal central D2-dopamine receptors by PET. Psychomacology (Berlin), 94, 471478.CrossRefGoogle Scholar
Farde, L., Wiesel, A., Nordstrom, A. L. & Sedvall, G. (1989) D1 - and D2- dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99, S28S31.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, A., Stone-Elander, S., et al (1990) D2 dopamine receptors in neuroleptic naïve schizophrenic patients: a positron emission tomography study with “C-raclopride. Archives of General Psychiatry, 47, 213219.CrossRefGoogle Scholar
Farde, L., Nordstrom, A. L., Wiesel, A., et al (1992) Positron emission tomographic analysis of central D1-and D2-dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Archives of General Psychiatry, 49, 538543.CrossRefGoogle ScholarPubMed
Farde, L., Nordstrom, A. L., Nyberg, S., et al (1994) D1-, D2- and 5HT2 receptor occupancy in clozapine treatment patients. Journal of Clinical Psychiatry, 55 (suppl. B), 6769.Google Scholar
Garbutt, J. C. & van Kammen, D. P. (1983) The interaction between GABA and dopamine: implications for schizophrenia. Schizophrenia Bulletin, 9, 336353.CrossRefGoogle ScholarPubMed
Grasby, P., Malizia, A. & Bench, C. (1996) Psychopharmacology – in vivo neurochemistry and pharmacology. British Medical Bulletin, 52, 513526.CrossRefGoogle ScholarPubMed
Gur, R. & Pearlson, G. (1993) Neuroimaging in schizophrenia research. Schizophrenia Bulletin, 19, 337353.CrossRefGoogle ScholarPubMed
Hall, H., Sedvall, G., Magnusson, O., et al (1994) Distribution of D1 dopamine and D2 dopamine receptors, dopamine and its metabolites in the human brain. Neuropsychopharmacology 11, 245256.CrossRefGoogle ScholarPubMed
Lyo, M. & Yamasaki, T. (1993) The detection of age related decrease of dopamine D1, D2 and serotonin 5-HT2 receptors in living human brain. Progress in Neuropsychopharmacology, Biology, Psychiatry, 17, 415421.Google Scholar
Johnstone, E. C., Crow, T. J., Frith, C. D., et al (1978) Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet, i, 848851.CrossRefGoogle Scholar
Kapur, S. & Remington, G. (1996) Serotonindopamine interaction and its relevance to schizophrenia. American Journal of Psychiatry, 153, 466473.Google ScholarPubMed
Kapur, S. & Remington, G., Jones, C., et al (1996) High levels of dopamine D2 receptor occupancy with low dose haloperidol treatment: a PET study. American Journal of Psychiatry, 153, 948950.Google ScholarPubMed
Kerwin, R. W. (1994) The new atypical antipsychotics. A lack of extrapyramidal side-effects and new routes for schizophrenia research. British Journal of Psychiatry, 164, 141148.CrossRefGoogle ScholarPubMed
Kerwin, R. W. & Pilowsky, L. (1994) The management of patients with schizophrenia. In Nuclear Medicine in Clinical Diagnosis and Treatment, vol. 1, pp. 607611. Edinburgh: Churchill Livingstone.Google Scholar
Kerwin, R. W. & Pilowsky, L. (1995) Traditional receptor theory and its application to neuroreceptor measurements in funtional images. European Journal of Nuclear Medicine, 22, 699710.CrossRefGoogle Scholar
Kessler, R., Scott Mason, N., Votaw, J. R., et al (1992) Visualization of extrastriatal dopamine D2 receptors in the human brain. European Journal of Pharmacology, 223, 105107.CrossRefGoogle ScholarPubMed
Knable, M. B., Heinz, A., Raedler, T., et al (1997) Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Psychiatry Research, 75, 91101.CrossRefGoogle ScholarPubMed
Koreen, A. R., Leiberman, J., Alvir, J., et al (1994) Plasma homovanillic acid levels in first episode schizophrenia – psychopathology and treatment response. Archives of General Psychiatry, 51, 132138.CrossRefGoogle ScholarPubMed
Laruelle, M., Abi-Dargham, A., van Dick, C. H., et al (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings of the National Academy of Sciences of the USA (Neurobiology), 93, 92359240.CrossRefGoogle Scholar
Lundberg, T., Lindstrom, L. H., Hartving, P., et al (1989) Striatal and frontal cortex binding of 11C-labelled clozapine visualised by positron emission tomography (PET) in drug-free schizophrenics and healthy volunteers. Psychopharmacology (Berlin), 99, 812.CrossRefGoogle ScholarPubMed
Mass, J. W., Bowden, C. L., Miller, A. L., et al (1997) Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations. Schizophrenia Bulletin, 23, 147154.CrossRefGoogle Scholar
Mackay, A. V. P., Iversen, L. L., Rossor, M., et al (1982) Increased brain dopamine and dopamine receptors in schizophrenia. Archives of General Psychiatry, 39, 991997.CrossRefGoogle ScholarPubMed
Martinot, J. L., Paillerd-Martinot, M. L., Loc'h, C., et al (1991) The estimated density of D2 striatal receptor in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. British Journal of Psychiatry, 158, 346350.CrossRefGoogle ScholarPubMed
Maziere, B. & Maziere, M. (1994) PET tracers for brain scanning. In Nuclear Medicine in Clinical Diagnosis and Treatment (eds Murray, I. P. C. & Ell, P. J.), vol. 1, pp. 519534. Edinburgh: Churchill Livingstone.Google Scholar
Meikle, S. R. & Dahlbom, M. (1994) Positron emission tomography. In Nuclear Medicine in Clinical Diagnosis and Treatment (eds Murray, I. P. C. & Ell, P. J.), vol. 2, pp. 13271337. Edinburgh: Churchill Livingstone.Google Scholar
Meltzer, H. Y. (1992) The importance of serotonin-dopamine interactions in the action of clozapine. British Journal of Psychiatry, 160 (suppl. 17), 2229.CrossRefGoogle Scholar
Murray, A. M., Ryoo, H. & Joyce, J. J. (1992) Visualization of dopamine D3-like receptors in human brain with 125I-epidepride. European Journal of Pharmacology (Molecular Pharmacology Section), 227, 443445.CrossRefGoogle Scholar
Nordstrom, A. L., Farde, L., Wiesel, A., et al (1993) Central D2 dopamine receptor occupancy in relation to antipsychotic drug effect: a double blind PET study of schizophrenic patients. Biological Psychiatry, 33, 227235.CrossRefGoogle ScholarPubMed
Nordstrom, A. L., Farde, L., Nyberg, S., et al (1995a) D1, D2, 5 HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. American Journal of Psychiatry, 152, 14441449.Google ScholarPubMed
Nordstrom, A. L., Farde, L., Eriksson, L. & Halldin, C. (1995b) No elevated D2 dopamine receptors in neuroleptic naive schizophrenic patients revealed by Positron Emission Tomography and 11C-N-Methylspiperone. Psychiatry Research, 61, 6783.CrossRefGoogle Scholar
Nordstrom, A. L., Nyberg, S., Olsson, H. & Farde, L. (1998) Positron EmissionTomography finding of high striatal D2 receptor occupancy in olanzapine treated patients. Archives of General Psychiatry, 55, 283283.CrossRefGoogle Scholar
Nyberg, S., Farde, L., Eriksson, L., et al (1993) 5HT2 and D2 dopamine receptor occupancy in the living human brain by risperidone. Psychopharmacology, 110, 265272.CrossRefGoogle ScholarPubMed
Nyberg, S., Farde, L. & Halldin, C. (1997) A PET study of 5-HT2 and D2 dopamine receptor occupancy induced by olanzapine in healthy subjects. Neuropsychopharmacology, 16, 17.CrossRefGoogle ScholarPubMed
Nyberg, S., Nakashima, Y., Nordstrom, A. L., et al (1996) PET studies of in-vivo binding characteristics of atypical antipsychotic drugs: review of D2 and 5HT2 receptor occupancy studies and clinical response. British Journal of Psychiatry, 168 (suppl. 29), 4044.CrossRefGoogle Scholar
Okubo, Y., Suhara, T., Suzuki, K., et al (1997) Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature, 385, 634636.CrossRefGoogle ScholarPubMed
Overall, J. E. & Gorham, D. E. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799812.CrossRefGoogle Scholar
Owens, D. G. C. (1996) Advances in psychopharmacology – schizophrenia. British Medical Bulletin, 52, 556574.CrossRefGoogle ScholarPubMed
Pazos, A., Probst, A. & Palacios, J. M. (1987) Serotonin receptors in the human brain-IV. Autoradiographic mapping of serotonin-2 receptors. Neuroscience, 21, 123139.CrossRefGoogle ScholarPubMed
Peroutka, S. J. & Snyder, S. H. (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic, and histamine receptors to clinical potency. American Journal of Psychiatry, 137, 15181522.Google ScholarPubMed
Perry, T. L., Hansen, S. & Jones, K. (1989) Schizophrenia, tardive dyskinesia, and brain GABA. Biological Psychiatry, 25, 200206.CrossRefGoogle ScholarPubMed
Pilowsky, L. (1992) Understanding schizophrenia. British Medical Journal, 305, 327328.CrossRefGoogle ScholarPubMed
Pilowsky, L., Costa, D., Ell, P. J., et al (1992) Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet, 340, 199202.CrossRefGoogle ScholarPubMed
Pilowsky, L., Costa, D., Ell, P. J., et al (1993) Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 1231-IBZM SPET (single photon emission tomography study). Psychological Medicine, 23, 791797.CrossRefGoogle ScholarPubMed
Pilowsky, L. & Kerwin, R. (1994) Nuclear medicine and drug studies in the brain. In Nuclear Medicine in Clinical Diagnosis and Treatment (eds Murray, P. C. & Ell, P. J.), vol. 1, pp. 629664. Edinburgh: Churchill Livingstone.Google Scholar
Pilowsky, L., Costa, D. C., Ell, P. J., et al (1994) D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients – an 1231-IBZM single photon emission computerised tomography study. British Journal of Psychiatry, 164, 1626.CrossRefGoogle ScholarPubMed
Pilowsky, L., Busatto, G., Taylor, M., et al (1996) Dopamine D2 receptor occupancy in vivo by the novel atypical antipsychotic olanzapine – an 1231-IBZM single photon emission tomography (SPET) study. Psychopharmacology, 124, 148153.CrossRefGoogle ScholarPubMed
Pilowsky, L., O'Connell, P., Davies, N., et al (1997a) In vivo effects on striatal dopamine D2 binding by the novel atypical antipsychotic drug sertindole – an l231-1BZM single photon emission tomography (SPET) study. Psychopharmacology, 130, 152158.CrossRefGoogle ScholarPubMed
Pilowsky, L., Mulligan, R. S., Acton, P. D., et al (1997b) Limbic selectivity of clozapine. Lancet, 350, 490491.CrossRefGoogle ScholarPubMed
Raedler, T. J., Knable, M. B., Lafague, T., et al (1998) Striatal dopamine D2 receptor occupancy in patients treated with olanzapine. Schizophrenia Research, 29, 166.CrossRefGoogle Scholar
Reynolds, G. P., Czudek, C. & Andrews, H. B. (1990) Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia. Biological Psychiatry, 27, 10381044.CrossRefGoogle ScholarPubMed
Sedvall, G. & Farde, L. (1995) Chemical brain anatomy in schizophrenia. Lancet, 346, 743749.CrossRefGoogle ScholarPubMed
Sedvall, G. & Farde, L., Persson, A. & Wiesel, F. A. (1986) Imaging of neurotransmitter receptors in the living human brain. Archives of General Psychiatry, 43, 9951005.CrossRefGoogle ScholarPubMed
Seeman, P. (1992) Elevated D2 in schizophrenia: role of endogenous dopamine and cerebellum. Commentary on the current status of PET scanning with respect to schizophrenia. Neuropsychopharmacology, 7(1), 5557.Google ScholarPubMed
Seibyl, J. P. (1995) Development of SPET as a tool for neuropsychopharmacological research. In Neuroimaging (ed. Kerwin, R.), vol. 3, pp. 5979. Cambridge: Cambridge University Press.Google Scholar
Simpson, M. D., Slater, P., Deakin, J. F., et al (1989) Reduced GABA uptake sites in the temporal lobe in schizophrenia. Neuroscience Letters, 107, 211215.CrossRefGoogle ScholarPubMed
Stephenson, C., Bigliani, V., Mulligan, R. S., et al (1998) Striatal and extrastriatal D2/D3 receptor blockade for the atypical antipsychotic quetiapine. Journal of Psychopharmacology, 12 (suppl. A53).Google Scholar
Stocklin, G. (1992) Tracers for metabolic imaging of brain and heart: radiochemistry and radiopharmacology. European Journal of Nuclear Medicine, 19, 527551.CrossRefGoogle ScholarPubMed
Suhara, T., Fukuda, H., Inoue, O., et al (1991) Age-related changes in humans D1 dopamine receptors measured by positron emission tomography. Psychopharmacology (Berlin), 103, 4145.CrossRefGoogle ScholarPubMed
Suhara, T., Kazuiko, N., Inoue, O., et al (1992) D1 dopamine receptor binding in mood disorders measured by positron emission tomography. Psychopharmacology, 106, 1418.CrossRefGoogle ScholarPubMed
Terriere, D., Abi-Dargham, A., Laruelle, M., et al (1995) Preliminary evaluation of a new 1- 123-labelled 5-HT2A receptor tracer in baboon with SPECT. European Journal of Nuclear Medicine, 22, 883.Google Scholar
Travis, M., Busatto, G., Pilowsky, L., et al (1997) In vivo 5-HT2A receptor blockade in schizophrenic patients treated with the broad spectrum atypical antipsychotics clozapine and olanzapine: preliminary SPET findings. Abstract, British Nuclear Medicine Society, 25th Annual Meeting, April.CrossRefGoogle Scholar
Trichard, C., Paillère-Martinot, M. L., Moufort, J. C., et al (1992) Cortical 5HT2 receptors and antipsychotic drugs studied with PET in schizophrenia: preliminary results. Anales de Psiquiatria, 8 (suppl. 1), 9.Google Scholar
Tune, L., Wong, D., Pearlson, G., et al (1993) Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with “C-N-Methylspiperone. Psychiatry Research, 49, 219237.CrossRefGoogle Scholar
van Kammen, D. P. (1977) y-Aminobutyric acid (GABA) and the dopamine hypothesis of schizophrenia. American Journal of Psychiatry, 134, 463464.Google Scholar
Verhoeff, N. P. L. G. (1994) Ligands for nueroreceptor imaging by single photon emission tomography (SPET) or positron emission tomography. In Nuclear Medicine in Clinical Diagnosis and Treatment (eds Murray, I. P. C. & Ell, P.J.), vol. 1, pp. 483518. Edinburgh: Churchill Livingstone.Google Scholar
Wagner, H. N., Burns, H. D., Dannals, R. F., et al (1983) Imaging dopamine receptors in the human brain by positron tomography. Science, 221, 12641266.CrossRefGoogle ScholarPubMed
Weinberger, D. R., Berman, K. F. & Zec, R. F. (1986) Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. Archives of General Psychiatry, 43, 114124.CrossRefGoogle ScholarPubMed
Westera, G., Buck, A., Bueger, C., et al (1996) Carbon-11 and iodine-123 labelled iomazenil: a direct PET-SPET comparison. European Journal of Nuclear Medicine, 23, 512.CrossRefGoogle Scholar
Wiesel, A., Farde, L., Nordstrom, A. L. & Sedvall, G. (1990) Central D1 - and D2 receptor occupancy during antipsychotic drug treatment. Progress in Neuropsychopharmacology and Biological Psychiatry, 14, 759767.CrossRefGoogle ScholarPubMed
Wolkin, A., Barouche, F., Wolf, A. P., et al (1989) Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. American Journal of Psychiatry, 146, 905908.Google ScholarPubMed
Wong, D., Wagner, H., Dannals, R., et al (1984) Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science, 226, 13931396.CrossRefGoogle ScholarPubMed
Wong, D., Wagner, H., Tune, L., et al (1986) Positron emission tomography reveals elevated D2 dopamine receptor in drug-naive schizophrenics. Science, 234, 15581563.CrossRefGoogle ScholarPubMed
Yousef, K. A., Volkow, N. D., Schlyer, D. J., et al (1995) Haloperidol blocks the uptake of 18F-N-methylspiperdol by extrastriatal dopamine receptors in schizophrenic patients. Synapse, 19, 1417.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.