Skip to main content
SpringerLink
Log in

Negative Symptoms in Schizophrenia: A Target for New Drug Development

  • Conference paper
Clinical Pharmacology in Psychiatry

Part of the book series: Psychopharmacology Series ((PSYCHOPHARM,volume 7))

Abstract

Delusions, hallucinations, and certain types of thought disorders, e. g., incoherence and illogicality, constitute the so-called positive symptoms in schizophrenia. It is unclear whether other kinds of thought disorder, e. g., looseness of associations, are also positive symptoms. The most important clinical effect of the current major classes of antipsychotic drugs, e. g., phenothiazines, butyrophenones, and thioxanthenes, is their ability to eliminate or significantly diminish positive symptoms in psychiatric patients, including those who meet narrow diagnostic criteria for schizophrenia. Positive symptoms are thought to be readily rated in most patients, at least in those who are not so guarded that they deny them or are mute and unable to confirm their presence or absence. The ability of antipsychotic drugs to diminish positive symptoms correlates highly with their ability to block dopamine D2 receptors (Seeman and Lee 1975), a characteristic which is readily ascertainable preclinically through a variety of methods. Because of these three factors — effectiveness, ease of clinical evaluation and preclinical predictability — much of the search for novel drug treatments in schizophrenia has focused on the alleviation of positive symptoms by dopamine receptor blockers which have a favorable side effect profile, desirable pharmacokinetic features, or both. Putative antipsychotics are then tested in patients, with the major focus on the rapid alleviation of positive symptoms. The net result is that antipsychotic drugs have a similar efficacy profile, with little to choose between them except side effects (Rifkin and Siris 1987).

Supported, in part, by USPHS MH 41594, MH 41684, and grants from the Cleveland and Sawyer Foundations. H.Y.M. is recipient of USPHS Research Career Scientist Award USPHS MH 47808

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 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
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

  • Andreasen NC (1982) Negative symptoms in schizophrenia: definition and reliability. Arch Gen Psychiatry 39: 784–788

    PubMed  CAS  Google Scholar 

  • Andreasen NC, Olsen S (1982) Negative vs positive schizophrenia: definition and validation. Arch Gen Psychiatry 39: 789–794

    PubMed  CAS  Google Scholar 

  • Angrist B, Rotrosen J, Gershon S (1980) Differential effects of amphetamine and neuroleptics on negative vs positive symptoms in schizophrenia. Psychopharmacology (Berlin) 72: 17–19

    Article  CAS  Google Scholar 

  • Bartko J J, Carpenter WT (1976) On the methods and theory of reliability. J Nerv Ment Dis 163: 307–312

    Article  PubMed  CAS  Google Scholar 

  • Berrios GE (1985) Positive and negative symptoms and Jackson: a conceptual history. Arch Gen Psychiatry 42: 95–97

    PubMed  CAS  Google Scholar 

  • Boronow J, Pickar D, Ninan PT, Roy A, Hommer D, Linnoila M, Paul SM (1985) Atrophy limited to IIIrd entricle only in chronic schizophrenic patients: report of a controlled series. Arch Gen Psychiatry 43: 266–271

    Google Scholar 

  • Carnoy P, Soubrie P, Puech AJ, Simon P (1986) Performance deficit induced by low doses of dopamine agonists in rats: toward a model for approaching the neurobiology of negative schizophrenic symptomatology? Biol Psychiatry 2: 11–22

    Article  Google Scholar 

  • Carpenter WT, Heinrichs DW, Alphs LD (1985) Treatment of negative symptoms. Schizophr Bull 11: 440–452

    PubMed  Google Scholar 

  • Claghorn J, Honigfeld G, Abuzzahab PS, Wang R, Steinbook R, Tuason V, Klerman G (1987) The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol 7: 377–384

    Article  PubMed  CAS  Google Scholar 

  • Crow TU (1980) Molecular pathology of schizophrenia: more than one disease process? Br Med J 280: 66–68

    Article  PubMed  CAS  Google Scholar 

  • Crow TJ (1985) The two syndrome concept: origins and current status. Schizophr Bull 11: 471–486

    PubMed  CAS  Google Scholar 

  • Endicott J, Spitzer RL (1978) A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 35: 837–844

    PubMed  CAS  Google Scholar 

  • Everitt BS, Gourlay A, Kendell R (1971) An attempt at validation of traditional psychiatric syndromes by cluster analysis. Br J Psychiatry 119: 399–412

    Article  PubMed  CAS  Google Scholar 

  • Fischer-Cornelssen KA, Ferner VJ (1976) An example of European multicenter trials: multi-spectral analysis of clozapine. Psychopharmacol Bull 12: 34–39

    PubMed  CAS  Google Scholar 

  • Fleiss JL, Gurland BJ, Cooper JE (1971) Some contributions to the treatment of psychopathology. Br J Psychiatry 119: 647–656

    Article  PubMed  CAS  Google Scholar 

  • Gelenberg AJ, Doller JC (1979) Clozapine versus chlorpromazine for the treatment of schizophrenia: preliminary results from a double blind study. J Clin Psychiatry 40: 238–240

    PubMed  CAS  Google Scholar 

  • Gerlach I, Koppelhus P, Helweg E, Mourad A (1974) Clozapine and haloperidol in a single- blind cross-over trial: therapeutic and biochemical aspects in the treatment of schizophrenia. Acta Psychiatr Scand 50: 410–424

    Article  PubMed  CAS  Google Scholar 

  • Gibbons RD, Lewine RJ, Davis JM, Schooler NR, Cole JO (1985) An empirical test of a Kraepelianan vs a bleulerian view of negative symptoms. Schizophr Bull 11: 390–396

    PubMed  CAS  Google Scholar 

  • Goldberg SC (1985) Negative and deficit symptoms in schizophrenia do respond to neuroleptics. Schizophr Bull 11: 453–456

    PubMed  CAS  Google Scholar 

  • Guirgius E, Voinesko G, Gray J, Schlieman E (1977) Clozapine (Leponex) vs Chlorpromazine (Largactil) in acute schizophrenia. (A double-blind controlled study). Curr Ther Res 21: 707–719

    Google Scholar 

  • Honigfeld G, Gillis R, Klett J (1966) A treatment-sensitive ward behavior scale. Psychol Rep 19: 180–182

    Article  PubMed  CAS  Google Scholar 

  • Jackman H, Luchins D, Meitzer HY (1983) Plasma serotonin levels in schizophrenia: relationship to race and psychopathology. Biol Psychiatry 18: 887–902

    PubMed  CAS  Google Scholar 

  • Kane J, Honigfeld G, Singer J, Meitzer H (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison versus chlorpromazine/benztropine. Arch Gen Psychiatry 48: 789–796

    Google Scholar 

  • Lewine RJ, Fogg L, Meitzer HY (1983) Assessment of negative and positive symptoms in schizophrenia. Schizophr Bull 9: 368–376

    PubMed  CAS  Google Scholar 

  • Liddle PF (1987) The symptoms of chronic schizophrenia: a reexamination of the positive- negative dichotomy. Br J Psychiatry 151: 145–151

    Article  PubMed  CAS  Google Scholar 

  • Lindstrom LH (1988) The effect of long-term treatment with clozapine in schizophrenia: a retrospective study in 96 patients treatment with clozapine for up to 13 patients. Acta Psychiatr Scand 17: 524–529

    Article  Google Scholar 

  • Luchins DJ, Lewine RJ, Meitzer HY (1984) Lateral ventricular size, psychopathology, and medication response in the psychoses. Biol Psychiatry 19: 29–44

    PubMed  CAS  Google Scholar 

  • Meltzer HY (1985) Dopamine and negative symptoms in schizophrenia: critique of the type I-type II hypothesis. In: Alpert M (ed) Controversies in schizophrenia: changes and constances. Guilford, New York, pp 110–136

    Google Scholar 

  • Meltzer HY (1986) Effect of neuroleptics on the schizophrenia syndrome. In: Dahl SG, Gram LF; Paul SM, Potter WZ (eds) Clinical pharmacology in psychiatry. Selectivity in psychotropic drug action — promises or problems? Springer, Berlin Heidelberg New York, pp 255–265

    Google Scholar 

  • Meltzer HY (1987) Biology of schizophrenia: an update. Schizophr Bull 13: 77–111

    PubMed  CAS  Google Scholar 

  • Meltzer HY (1988) Clozapine: clinical advantages and biological mechanisms. In: Schulz C, Tamminga C (eds) Schizophrenia: a scientific focus. International Conference on Schizophrenia. University of Oxford Press, New York

    Google Scholar 

  • Meltzer HY, Sommers AA, Luchins DJ (1986) The effect of neuroleptics and other psychotropic drugs on negative symptoms in schizophrenia. J Clin Psychopharmacol 6: 329–338

    Article  PubMed  CAS  Google Scholar 

  • Mita T, Hanada S, Nishino N, Kuno T, Nakai H, Yamadori T, Mizoi Y, Tanaka C (1986) Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol Psychiatry 21: 1407–1414

    Article  PubMed  CAS  Google Scholar 

  • Niskanen P, Achte K, Jaskari M, Karesga M, Meisted B, Nilsson LB, Rontavaara M, et al. (1974) Results of a comparative double-blind study with clozapine and chlorpromazine in the treatment of schizophrenic patients. Psychiatr Fenn 307–313

    Google Scholar 

  • Ota T, Maeshiro H, Ishido H, Shimizu Y, Uchida R, Toyoshima R, Ohshima H, et al. (1987) Treatment resistant chronic psychopathology and CT scans in schizophrenia. Acta Psychiatr Scand 75: 415–427

    Article  PubMed  CAS  Google Scholar 

  • Overall JE, Gorham D (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10: 799–812

    Google Scholar 

  • Pearlson JD, Veroff AE (1981) Computerized tomographic scan changes in manic-depressive illness. Lancet 2: 470

    Article  PubMed  CAS  Google Scholar 

  • Prien RF, Cole JO (1968) High dose chlorpromazine therapy in chronic schizophrenia. Arch Gen Psychiatry 18: 482–495

    Google Scholar 

  • Rifkin A, Siris S (1987) Drug treatment of schizophrenia. In: Meitzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York, pp 1095–1101

    Google Scholar 

  • Seeman P, Lee T (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188: 1217–1219

    Article  PubMed  CAS  Google Scholar 

  • Smith RC, Baumgartner R, Ravichandran GK, Largen J, Calderon M, Burd A, Mauldin M (1987) Cortical atrophy and white matter density in the brains of schizophrenics and clinical response to neuroleptics. Acta Psychiatr Scand 75: 11–19

    Article  PubMed  CAS  Google Scholar 

  • Spitzer RL, Fleiss JL, Endicott J, Cohen J (1967) Mental Status Schedule: properties of factor analytically derived scales. Arch Gen Psychiatry 16: 479–493

    PubMed  CAS  Google Scholar 

  • Strauss JS, Carpenter WT Jr, Bartko J J (1974) The diagnosis and understanding of schizophrenia. III. Speculations on the processes that underlie schizophrenic symptoms and signs. Schizophr Bull 1: 61–69

    Google Scholar 

  • Trimble MR (1986) Positive and negative symptoms in schizophrenia. Br J Psychiatry 148: 587–589

    Article  PubMed  CAS  Google Scholar 

  • Weinberger DR, Bigelow LB, Kleinman JL, Klein ST, Rosenblatt JE, Wyatt RT (1980) Cerebral ventricular enlargement in chronic schizophrenia: an association with poor response to treatment. Arch Gen Psychiatry 37: 11–13

    PubMed  CAS  Google Scholar 

  • Williams AO, Reveley MA, Kolakowska T, Andern M, Mandlebrote BM (1985) Schizophrenia with good and poor outcome. II. Cerebral ventricular size and its clinical significance. Br J Psychiatry 147: 239–246

    Article  Google Scholar 

  • Wing JK (1978) Clinical concepts of schizophrenia. In: Schizophrenia: toward a new synthesis. Academic, London, pp 1–30

    Google Scholar 

  • Wing JK, Cooper JE, Sartorius N (1974) Measurement and classification of psychiatric symptoms. An instructional manual for the PSE and Catego Program. Cambridge University Press, Cambridge

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA

    J. Zureick

Authors
  1. H. Y. Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Zureick
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Institute of Medical Biology, University of Tromsø School of Medicine, 9001, Tromsø, Norway

    Svein G. Dahl (Professor of Pharmacology) (Professor of Pharmacology)

  2. Department of Clinical Pharmacology, School of Medicine, Odense University, 5000, Odense C, Denmark

    Lars F. Gram (Professor of Clinical Pharmacology) (Professor of Clinical Pharmacology)

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Meltzer, H.Y., Zureick, J. (1989). Negative Symptoms in Schizophrenia: A Target for New Drug Development. In: Dahl, S.G., Gram, L.F. (eds) Clinical Pharmacology in Psychiatry. Psychopharmacology Series, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74430-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74430-3_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74432-7

  • Online ISBN: 978-3-642-74430-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation