Prediction of clinical response to neuroleptics and positron emission tomography in schizophrenia

  • M. S. Buchsbaum
  • C. T. Luu
Conference paper


Every clinician knows that some schizophrenics show marked improvement in symptoms when treated even with low doses of neuroleptics and others show little improvement or even worsening when medication is given (Carpenter et al. 1981, Brown et al. 1989, Garver et al. 1988). This diversity in treatment response may be especially marked in university research programs where patients who are having their first psychotic episode as well as those who are chronically ill and especially medication resistent may appear. The variation in clinical effects of typical antipsychotic drugs may be explained by the density, affinity, and pharmacological class of receptors with which they interact. Furthermore, individual differences in the pharmacokinetics of antipsychotic drugs, biological heterogeneity in schizophrenia and the particular cerebral regions whose functions are altered directly or indirectly by their administration will play a role on the clinical outcome. Imaging is an insightful pathway into understanding and unraveling some of these variations. The imaging of regional cerebral metabolism can provide information about the initial state of the patient’s brain and the functional consequences of neuroleptic administration throughout the brain.


Positron Emission Tomography Metabolic Rate Positron Emission Tomographic Continuous Performance Test Glucose Metabolic Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci 9:357–381.PubMedCrossRefGoogle Scholar
  2. Bartlett EJ, Wolkin A, Brodie JD, Laska EM, Wolf AP (1991) Importance of pharmacologic control in PET studies: effects of thiothixene and haloperidol on cerebral glucose utilization in chronic schizophrenia. Psychiatry Res: Neuroimaging 40:115–124.PubMedCrossRefGoogle Scholar
  3. Brown WA, Herz LR (1989) Response to neuroleptic drugs as a device for classifying schizophrenia. Schizophr Bull 15:123–129.PubMedGoogle Scholar
  4. Buchsbaum MS (1993) Critical review of psychopathology in twins: structural and functional imaging of the brain. In: Bouchard TJ Jr, Propping P (eds) Twins as a tool of behavioral genetics. John Wiley, Sussex, pp 257–271.Google Scholar
  5. Buchsbaum MS, Gillin JC, Wu J, Hazlett E, Sicotte N, DuPont RM (1989) Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography. Life Sci 45:1349–1356.PubMedCrossRefGoogle Scholar
  6. Buchsbaum MS, Haier RJ, Potkin SG, Nuechterlein K, Bracha S, Lohr J, Wu J, Lottenberg S, Jerabek PA, Trenary M, Tafalla R, Reynolds C, Bunney WE Jr (1992) Fronto-striatal disorder of cerebral metabolism in never-medicated schizophrenics. Arch Gen Psychiatry 49:935–942.PubMedCrossRefGoogle Scholar
  7. Buchsbaum MS, Ingvar DH, Kessler R, Waters RN, Cappelletti J, van Kammen DP, King AC, Johnson JJ, Manning RG, Flynn RM, Mann LS, Bunney WE, Sokoloff L (1982) Cerebral glucography with positron tomography in normals and in patients with schizophrenia. Arch Gen Psychiatry 39:251–259.PubMedCrossRefGoogle Scholar
  8. Buchsbaum MS, Mirsky AF, DeLisi LE, Morihisa J, Karson CN, Mendelson WB, King AC, Johnson J, Kessler R (1984) The Genain quadruplets: electrophysiological, positron emission and X-ray tomographic studies. Psychiatry Res 13:95–108.PubMedCrossRefGoogle Scholar
  9. Buchsbaum MS, Nuechterlein KH, Haier RJ, Wu J, Sicotte N, Hazlett E, Asarnow R, Potkin S, Guich S (1990) Glucose metabolic rate in normals and schizophrenics during the continuous performance test assessed by positron emission tomography. Br J Psychiatry 156:216–227.PubMedCrossRefGoogle Scholar
  10. Buchsbaum MS, Potkin SG, Marhall JF, Lottenberg S, Tang CY, Heh CW, Tafalla R, Reynolds C, Abel L, Plon L, Bunney WE Jr (1992) Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia. Neuropsychopharmacology 6(3): 155–163.PubMedGoogle Scholar
  11. Buchsbaum MS, Potkin SG, Siegel BV, Lohr J, Katz M, Gottschalk LA, Gulasekaram B, Marshall JF, Lottenberg S, Teng CY, Abel L, Plon L, Bunney WE (1992) Striatal metabolic rate and clinical response to neuroleptics in schizophrenia. Arch Gen Psychiatry 49:966–974.PubMedCrossRefGoogle Scholar
  12. Buchsbaum MS, Siegel BV (1994) Neuroimaging and the aging process in psychiatry. Int Rev Psychiatry 6:109–118.CrossRefGoogle Scholar
  13. Buchsbaum MS, Tafalla RJ, Reynolds C, Trenary M, Burgwald L, Potkin S, Bunney WE Jr (1991) Drug effects on brain lateralization in the basal ganglia of schizophrenics. In: Willner P, Scheel-Kruger J (eds) The mesolimbic system: from motivation to action. John Wiley, Sussex, pp 529–538.Google Scholar
  14. Buchsbaum MS, Wu JC, DeLisi LE, Holcomb HH, Hazlett E, Cooper-Langston K, Kessler R (1987) Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients. Biol Psychiatry 22:479–494.PubMedCrossRefGoogle Scholar
  15. Bunney WE Jr (1988) A view of the neurosciences and psychopharmacology of the major psychoses — present and future. CINP, Munich, Germany (Abstract).Google Scholar
  16. Bunney WE Jr (1990) Dopamine glutamate interactions in schizophrenia. American College of Neuropsychopharmacology (ACNP), San Juan, Puerto Rico, December 10–14, p 44 (Abstract).Google Scholar
  17. Carlsson M, Carlsson A (1990) Schizophrenia: a subcortical neurotransmitter imbalance syndrome? Schizophr Bull 16:425–432.PubMedGoogle Scholar
  18. Carpenter WT Jr, Heinrichs DW (1981) Treatment-relevant subtypes of schizophrenia. J Nerv Ment Dis 169:113–119.PubMedCrossRefGoogle Scholar
  19. Cleghorn JM, Szechtman H, Garnett ES, Nahmias C, Brown GM, Kaplan RD, Szechtman B, Franco S (1991) Apomorphine effects on brain matabolism in neuroleptic-naive schizophrenic patients. Psychiatry Res: Neuroimaging 40:135–153.PubMedCrossRefGoogle Scholar
  20. Cohen G, Andreasen NC, Allinger R, Arndt S, Kuan J, Yuh W, Ehrhardt J (1992) Segmentation techniques for the classification of brain tissue using magnetic resonance imaging. Psychiatry Res: Neuroimaging 45:33–51.PubMedCrossRefGoogle Scholar
  21. Cornblatt BA, Lenzenweger MF, Ertenmeyer-Kimting L (1989) The continuous performance test, idential pairs version. II. Contrasting attentional profiles in schizophrenic and depressed patients. Psychiatry Res 29:65–85.PubMedCrossRefGoogle Scholar
  22. Dixon WJ (1982) BMD Biomedical computer programs. University of California Press, Berkeley Ca.Google Scholar
  23. DeLisi LE, Mirsky AF, Buchsbaum MS, van Kamme DP, Berman KF, Caton C, Kafka MS, Ninan PT, Phelps BH, Karoum F, Ko GN, Korpi EN, Linnoila M, Scheinin M, Wyatt RJ (1984) The Genain quadruplets 25 years later: a diagnostic and biochemical follow up. Psychiatry Res 13:59–76.PubMedCrossRefGoogle Scholar
  24. Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231:258–261.PubMedCrossRefGoogle Scholar
  25. Garver DL, Kelly K, Fried KA, Magnusson M, Hirschowitz J (1988) Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias). Psychol Med 18:873–885.PubMedCrossRefGoogle Scholar
  26. Harris GJ, Pearlson GD (1993) MRI-guided region of interest placement on emission computed tomograms. Psychiatry Res: Neuroimaging 50:57–63.PubMedCrossRefGoogle Scholar
  27. Iyo M, Nishiro M, Itoh T, Fukuda H, Suzuki K, Yamasaki T, Fukui S, Tateno Y (1992) Dopamine D2 and serotonin2 receptors in susceptibility to methamphetamine psychosis detected by positron emission tomography. Psychiatry Res: Neuroimaging 50(4):217–231.CrossRefGoogle Scholar
  28. Joyce JN, Lexow N, Bird E, Winokur A (1988) Organization of dopmaine D1 and D2 receptors in human striatum: receptor autoradiographic studies in huntington’s disease and schizophrenia. Synapse 2:546–557.PubMedCrossRefGoogle Scholar
  29. Matsui T, Hirano A (1978) An atlas of the human brain for computerized tomography. Igaku-Shoin, Tokyo.Google Scholar
  30. Mirksy AF, DeLisi LE, Buchsbaum MS, Quinn OW, Schwerdt P, Siever LJ, Mann L, Weingartner H, Zec R, Sostek A, Alterman I, Revere I, Dawson SD, Zahn TP (1984) The Genain quadruplets: psychological studies. Psychiatry Res 13:77–93.CrossRefGoogle Scholar
  31. Nuechterlein KH, Parasuraman R, Jiang Q (1983) Visual sustained attention: image degradation produces rapid decrement over time. Science 220:327–329.PubMedCrossRefGoogle Scholar
  32. Overall JE, Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10:799–812.CrossRefGoogle Scholar
  33. Rosenthal D (1963) The Genain quadruplets. Basic Books, New York.Google Scholar
  34. Siegel BV, Buchsbaum MS, Bunney WE, Gottschalk LA, Haier RJ, Lohr JB, Lottenberg S, Najafi A, Nuechterlein KH, Potkin SG, Wu JC (1993) Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic. Am J Psychiatry 150:1325–1336.PubMedGoogle Scholar
  35. Tune LE, Wong DF, Pearlson G, Strauss M, Young T, Shaya EK, Dannals RF, Wilson AA, Ravert HT, Sapp J, Cooper T, Chase GA, Wagner HN Jr (1993) Dopamine D2receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone. Psychiatry Res 49(3):219–237.PubMedCrossRefGoogle Scholar
  36. Wolkin A, Angrist B, Wolf A, Brodie J, Wolkin B, Jaeger J, Cancro R, Rotrosen J (1987) Effects of amphetamine on local cerebral metabolism in normal and schizophrenic subjects as determined by positron emission tomography. Psychopharmacology 92:241–246.PubMedCrossRefGoogle Scholar
  37. Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung TJK, Malat J, Williams JA, O’Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558–1563.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1994

Authors and Affiliations

  • M. S. Buchsbaum
    • 1
    • 2
  • C. T. Luu
    • 1
  1. 1.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA
  2. 2.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA

Personalised recommendations