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Antipsychotic medication, D2 dopamine receptor blockade and clinical response: a 123I IBZM SPET (single photon emission tomography) study

Published online by Cambridge University Press:  09 July 2009

L. S. Pilowsky ,
D. C. Costa ,
P. J. Ell ,
R. M. Murray ,
N. P. L. G. Verhoeff  and
R. W. Kerwin
L. S. Pilowsky*
Affiliation:
Institute of Psychiatry; and Institute of Nuclear Medicine, UCMSM, London; and Amsterdam Medical Centre, Cygne b.v., Eindhoven University, The Netherlands
D. C. Costa
Affiliation:
Institute of Psychiatry; and Institute of Nuclear Medicine, UCMSM, London; and Amsterdam Medical Centre, Cygne b.v., Eindhoven University, The Netherlands
P. J. Ell
Affiliation:
Institute of Psychiatry; and Institute of Nuclear Medicine, UCMSM, London; and Amsterdam Medical Centre, Cygne b.v., Eindhoven University, The Netherlands
R. M. Murray
Affiliation:
Institute of Psychiatry; and Institute of Nuclear Medicine, UCMSM, London; and Amsterdam Medical Centre, Cygne b.v., Eindhoven University, The Netherlands
N. P. L. G. Verhoeff
Affiliation:
Institute of Psychiatry; and Institute of Nuclear Medicine, UCMSM, London; and Amsterdam Medical Centre, Cygne b.v., Eindhoven University, The Netherlands
R. W. Kerwin
Affiliation:
Institute of Psychiatry; and Institute of Nuclear Medicine, UCMSM, London; and Amsterdam Medical Centre, Cygne b.v., Eindhoven University, The Netherlands
*
1Address for correspondence: Dr L. S. Pilowsky, Genetics Section, Institute of Psychiatry, De Crespigny Park, London SE5 8AF.
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Synopsis

The hypothesis that poor response to antipsychotic medication is due to inadequate occupancy of central D2 receptors was tested in vivo. We assessed striatal D2 dopamine receptor availability for binding with the specific ligand 123I IBZM by single photon emission tomography (SPET) in two groups of DSM-III-R diagnosed schizophrenic patients on typical antipsychotic medication, and a group of healthy controls (N = 20). Patients were characterized by clinical ratings as antipsychotic responders (N = 10) or non-responders (N = 8). Dynamic single slice SPET, at a slice chosen to include the basal ganglia, began immediately following intravenous injection of 185 MBq 123I IBZM. Semiquantitative analysis generated indices of D2 receptor availability for binding. There was no difference in striatal D2 receptor availability between the patient groups, both showing a similar degree of occupancy by antipsychotic medication compared to the control group. Thus, poor clinical response does not appear to be accounted for by differential blockade, or inadequate occupancy of striatal dopamine D2 receptors by antipsychotic medication.

Type
Preliminary Communication
Information
Psychological Medicine , Volume 23 , Issue 3 , August 1993 , pp. 791 - 797
Copyright
Copyright © Cambridge University Press 1993

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References

Abnormal Involuntary Movements Scale (AIMS) (1974). Alcohol, Drug Abuse, and Mental Health Administration, Department of Health, Education and Welfare: Washington, DC.Google Scholar
Alavi, A., Velchick, M. G., Kung, H. F., Kung, M. P., Chang, W., Noto, R., Pan, S., Billings, J., Sorgentoni, K., Rauch, A. & Reilley, J. (1989). Imaging the basal ganglia in the human brain with I-123-IBZM: a new CNS D2 receptor agent. Journal of Nuclear Medicine 30, 731.Google Scholar
American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn. (revised). APA: Washington, DC.Google Scholar
Baldessarini, R. J., Cohen, B. M. & Teicher, M. H. (1988). Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. Archives of General Psychiatry 45, 79–91.Google Scholar
Brucke, T., Podrecka, I., Angelberger, P., Wenger, S., Topitz, A., Kufferle, B., Muller, Ch. & Deecke, L. (1991). Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders. Journal of Cerebral Blood Flow and Metabolism 11, 220–228.Google Scholar
Brucke, T., Roth, J., Podrecka, I., Strobi, R., Wenger, S. & Asenbaum, S. (1992). Striatal dopamine D2 blockade by typical and atypical neuroleptics. Lancet 339, 497.Google Scholar
Camps, M., Cortes, R., Gueye, B., Probst, A. & Palacios, J. M. (1989). Dopamine receptors in human brain, autoradiographic distribution of D2 sites. Neuroscience 28, 275–290.Google Scholar
Costa, D. C., Verhoeff, N. P. L. G., Cullum, I., Ell, P. J., Syed, G. S., Barrett, J., Palazidou, E., Toone, B., Van Royen, E. & Bobeldijk, M. (1990). In vivo characterisation of 3-iodo-6-methoxybenzamide 123I in humans. European Journal of Nuclear Medicine 16, 813–816.Google Scholar
Coppens, H. J., Slooff, C. J., Paans, A. M. J., Weigman, T., Vaalburg, W. & Korf, J. (1991). High central D2-dopamine receptor occupancy as assessed with positron emission tomography in medicated but therapy-resistant patients. Biological Psychiatry 29, 629–634.Google Scholar
Endicott, J., Spitzer, R. L., Fleiss, J. L. & Cohen, J. (1976). The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry 33, 766–771.Google Scholar
Farde, L., Wiesel, F. A., Nordstrom, A.-L. & Sedvall, G. (1989). D1, and D2 dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology 99, S28–S31.Google Scholar
Farde, L., Wiesel, F. A., Stone-Elander, S., Halldin, C., Nordstrom, A.-L., Hall, H. & Sedvall, G. (1990). D2 dopamine receptors in neuroleptic naive schizophrenic patients. Archives of General Psychiatry 47, 213–219.Google Scholar
Kane, J., Honigfeld, G., Singer, J., Meltzer, H. & the Clozaril Collaborative Study Group (1988). Clozapine for the treatment-resistant schizophrenic. Archives of General Psychiatry 45, 789–796.Google Scholar
Kolakowska, T., Williams, A. O., Ardern, M., Revely, M. A., Jambor, K., Gelder, M. G. & Mandelbrote, B. M. (1985). Schizophrenia with good and poor outcome I. Early clinical features, response to neuroleptics and signs of organic dysfunction. British Journal of Psychiatry 146, 229–246.Google Scholar
Kung, H. F., Pan, S., Kung, M.-P., Billings, J., Kasliwal, R., Reilley, J. & Alavi, A. (1989). In vitro and in vivo evaluation of 123I IBZM: a potential CNS D2 dopamine receptor imaging agent. Journal of Nuclear Medicine 30, 88–92.Google Scholar
Martinot, J.-L., Paillière-Martinot, M. L., Loc'h, C., Hardy, P., Poirier, M. F., Mazoyer, B., Beaufils, B., Mazière, B., Allilaire, J. P. & Syrota, A. (1991). The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. British Journal of Psychiatry 158, 346–350.Google Scholar
Overall, J. E. & Gorham, D. E. (1962). The brief psychiatric rating scale. Psychological Reports 10, 799–812.Google Scholar
Pilowsky, L. S., Costa, D. C., Ell, P. J., Verhoeff, N. P. L. G., Murray, R. M. & Kerwin, R. W. (1992). Clozapine, single photon emission tomography and the dopamine D2 blockade hypothesis of schizophrenia. Lancet 340, 199–202.Google Scholar
Pilowsky, L. S., Costa, D. C., Ell, P. J., Verhoeff, N. P. L. G., Murray, R. M. & Kerwin, R. W. (1993). D2 dopamine receptor binding in the basal ganglia of antipsychotic free schizophrenic patients – a 123I IBZM single photon emission tomography (SPET) study. British Journal of Psychiatry (in the press).Google Scholar
Smith, M., Wolf, A. P., Brodie, J. D., Arnett, C. D., Barouche, F., Shiue, C.-Y., Fowler, J. S., Russell, J. A. G., MacGregor, R. R., Wolkin, A., Angrist, B., Rotrosen, J. & Peselow, E. (1988). Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biological Psychiatry 23, 653–663.Google Scholar
Van Putten, T. V., Marder, S. R. & Mintz, J. (1990). A controlled dose comparison of haloperidol in newly admitted schizophrenic patients. Archives of General Psychiatry 47, 754–758.Google Scholar
Verhoeff, N. P. L. G., Costa, D. C., Ell, P. J., Toone, B., Palazidou, E., Cullum, I. D., Bobeldijk, M., Miller, R., Syed, G. M. S., Soricelli, A. & Van Royen, E. A. (1990). Dopamine D-2-receptor imaging with dynamic I-123.IBZM SPET in patients with schizophrenia or HIV encephalopathy. In Nuclear Medicine-the Slate of the Art of Nuclear Medicine in Europe (ed. Schmidt, H. A. E. and van der Schoot, J. B.), pp. 207–212. Schattauer: Stuttgart, Germany.Google Scholar
Wolkin, A., Barouche, F., Wolf, A. P., Rotrosen, J., Fowler, J. S., Shiue, C.-Y., Cooper, T. B. & Brodie, J. D. (1989). Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. American Journal of Psychiatry 146, 905–908.Google Scholar
Wressell, S. E., Tyrer, S. P. & Berney, T. P. (1990). Reduction in antipsychotic drug dosage in mentally handicapped patients – a hospital study. British Journal of Psychiatry 157, 101–106.Google Scholar