Skip to main content Accessibility help
×
Home

Genetic factors in the response to neuroleptics in schizophrenia: a psychopharmacogenetic study

  • Joe Galdi (a1), Ronald O. Rieder (a1), David Silber (a1) and Roland R. Bonato (a1)

Synopsis

A psychopharmacogenetic strategy was used to investigate a genetic heterogeneity model of schizophrenia. This model consisted of various genetic subtypes represented by patients classified hypothetically according to the types and genealogical (Mendelian) patterns of illnesses in first-degree relatives. The effect of neuroleptics on these subtypes (drug x genetic subtype interactions) were tested for evidence of post-treatment responses which discriminated between them. The findings revealed that schizophrenics who had depressed relatives tended to exhibit (1) depression and more severe pseudoparkinsonism irrespective of types of neuroleptics, and (2) greater remission of paranoid-hostility symptoms when treated with neuroleptics of the aliphatic-piperadine type. Schizophrenics who had schizophrenic relatives failed to show these responses.

Interpretation of these findings emphasized the recognition of these responses as arising from neuroleptic-induced alterations of defective neurologic-neurochemical systems underlying this subtype and as ‘pharmacogenetic criteria’ by which it can be discriminated.

Copyright

Corresponding author

1Address for correspondence: Dr Joe Galdi, Department of Psychiatry, University of Cincinnati College of Medicine, Rm 7303, MSB, Cincinnati, OH 45267, USA.

References

Hide All
Akiskal, H. S. & McKinney, W. T. (1975). Overview of recent research in depression. Archives of General Psychiatry 32, 285305.
Akiskal, H. S. & Webb, W. L. (1978). Psychiatric Diagnosis: Explorations of Biological Predictors. Spectrum: New York.
d'Alarcón, R. & Carney, M. W. P. (1969). Severe depressive mood changes following slow-release intramuscular fluphenazine injection. British Medical Journal i, 564567.
American Psychiatric Association (1952). Diagnostic and Statistical Manual of Mental Disorders (DSM-I). APA: Washington, D.C.
American Psychiatric Association (1968). Diagnostic and Statistical Manual of Mental Disorders (DSM-II). APA: Washington, D.C.
American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders (DSM-III). APA: Washington, D.C.
Appleton, W. S. (1976). Third psychoactive drug usage guide. Diseases of the Nervous System 37, 3951.
Astrup, C. (1979). The Chronic Schizophrenias. Universitets-forlaget: Oslo.
Avrutskii, G. Y. (1964). Some unfavorable effects of aminazine medication on the manifestations and course of schizophrenia. In Problems of Psychopharmacology (ed. Rokhlin, L. L.), pp. 6172. Davey: New York.
Bonato, R. R., Guy, W., Cleary, P. & Yang, K. (1970). BLIPS: the information processing system for the ECDEU program. Psychopharmacology Bulletin 6, 2247.
Bowers, M. B. & Astrachan, B. M. (1967). Depression in acute schizophrenic psychosis. American Journal of Psychiatry 123, 976979.
Bunney, B. S. & Aghajanian, G. K. (1978). Mesolimbic and mesocortical dopaminergic systems: physiology and pharmacology. In psychopharmacology: A Generation of Progress (ed. Lipton, M. A., DiMascio, A. and Killiam, K. F.), pp. 159169Raven Press: New York.
Burdock, E. I., Hakerem, G., Hardesty, A. S. & Zubin, J. (1960). A ward behavior scale for use with mental hospital patients. Journal of Clinical Psychology 16, 246247.
Carlsson, A. (1978). The neuropharmacology of schizophrenia: specificity for neurotransmitter systems. In Psychiatric Diagnosis: Exploration of Biological Predictors (ed. Akiskal, H. S. and Webb, W. L.), pp. 247262. Spectrum: New York.
Carpenter, W. T., McGlashan, T. H. & Strauss, J. S. (1977). The treatment of acute schizophrenia without drugs: an investigation of some current assumptions. American Journal of Psychiatry 134, 1420.
Casey, J. F., Bennett, I. F. & Lindley, C. J. (1960). Drug therapy of schizophrenia: a controlled study of the relative effectiveness of chlorpromazine, promazine, phenobarbitol, and placebo. Archives of General Psychiatry 117, 9971003.
Celesia, G. G. & Wanamaker, W. M. (1972). Psychiatric disturbances in Parkinson's disease. Diseases of the Nervous System 33, 577582.
Cooper, J. R., Bloom, F. E. & Roth, R. H. (1978). The Biochemical Basis of Neuropharmacology. Oxford: New York.
Davis, J. M. (1976). Comparative doses and costs of antipsychotic medication. Archives of General Psychiatry 33, 858861.
Donlon, P. T. & Stenson, R. L. (1976). Neuroleptic induced extrapyramidal symptoms. Diseases of the Nervous System 37, 629635.
Donlon, P. T., Rada, R. T. & Arora, K. K. (1976). Depression and the reintegration phase of acute schizophrenia. American Journal of Psychiatry 133, 12651268.
Duvoisin, R. C. (1968). Neurological reactions to psychotropic drugs. In psychopharmacology: A Review of Progress 1957–1967 (ed. Efron, D. H.), pp. 561574. PHS No. 1836. US Government Printing Office: Washington, D.C.
Eleftheriou, B. E. (ed.) (1975). Psychopharmacogenetics. Plenum Press: New York.
Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A., Winokur, G. & Munoz, R. (1972). Diagnostic criteria for use in psychiatric research. Archives of General Psychiatry 26, 5763.
Fish, F. J. (1962). Schizophrenia. Williams & Wilkins: Baltimore.
Floru, L., Heinrich, K. & Wittek, F. (1975). The problem of postpsychotic schizophrenic depression and their pharmacological induction. International Pharmacopsychiatry 10, 230239.
Food and Drug Administration (1977). General Considerations for the Clinical Evaluation of Drugs. HEW (FDA) No. 77–3040. US Government Printins, Office: Washington, D.C.
Fowler, R. C., McCabe, M. S., Cadoret, R. J. & Winokur, G. (1972). The validity of good prognosis schizophrenia. Archives of General Psychiatry 26, 182185.
Galdi, J., Rieder, R. O. & Bonato, R. (1981 a). Pharmacogenetic predictors of length of hospital stay in recently admitted schizophrenics. (Submitted for publication.)
Galdi, J., Kelly, J. T., Rieder, R. O., Bonato, R. R. & Schiele, B. C. (1981 b). A test of the validity of pharmacogenetic pseudoparkinsonism in schizophrenia. (Submitted for publication.)
Gallant, D. M., Bishop, M. P., Free, S. M., Goldberg, S. C. & Simpson, G. M. (1971). Evaluation of efficacy of psychotropic agents in schizophrenic populations. In Principles and Problems in Establishing the Efficacy of Psychotropic Agents (ed. Levine, J., Schiele, B. and Bouthilet, L.), pp. 5990. US Government Printing Office: Washington, D.C.
Gershon, E. S., Bunney, W. E., Leckman, J. F., Van Eerdewegh, M. & DeBauche, B. A. (1976). The inheritance of affective disorders: a review of data and hypotheses. Behavior Genetics 6, 227261.
Goldberg, S. C., Cole, S. C. & Clyde, D. J. (1963). Factor analysis of ratings of schizophrenic behavior. Psychopharmacology Service Center Bulletin 2, 2328.
Goldstein, M. J. (1970). Premorbid adjustment, paranoid status, and patterns of response to phenothiazine in acute schizophrenia. Schizophrenia Bulletin 3, 2437.
Gottesman, I. I. & Shields, J. (1976). A critical review of recent adoption, twin, and family studies of schizophrenia: behavioral genetics perspectives. Schizophrenia Bulletin 2, 360400.
Guy, W. (1976). ECDEU Assessment Manual For Psychopharmacology (Revised). DHEW No. (ADM) 76338. US Government Printing Office: Washington, D.C.
Guy, W., Cleary, P. & Bonato, R. R. (1974). Methodological considerations of a large central data system. In Neuropsychopharmacology, pp. 7987. International Congress Series No. 359. Excerpta Medica: Amsterdam.
Hartmann, W., Kind, J., Meyer, J. E., Muller, P. & Steuber, H. (1980). Neuroleptic drugs and the prevention of relapse in schizophrenia: a workshop report. Schizophrenia Bulletin 6, 536543.
Hogarty, G. E., Schooler, N. R., Ulrich, R., Mussare, F., Ferro, P. & Herron, E. (1979). Fluphenazine and social therapy in the aftercare of schizophrenic patients. Archives of General Psychiatry 36, 12831294.
Honigfeld, G., Gillis, R. D. & Klett, C. J. (1966). NOSIE-30: a treatment sensitive ward behavior scale. Psychological Reports 19, 180182.
Inouye, E. (1963). Similarity and dissimilarity of schizophrenia in twins. Proceedings of the Third World Congress of Psychiatry 1, 524530.
Kalow, W. & LaBlanc, A. E. (1975). Implications of psychopharmacogenetic research. In Psychopharmacogenetics (ed. Eleftheriou, B. E.), pp. 3342. Plenum Press: New York.
Kayton, L., Beck, J. & Koh, S. D. (1976). Postpsychotic state, convalescent environment, and therapeutic relationship in schizophrenic outcome. American Journal of Psychiatry 133, 12691274.
Kerlinger, F. N. & Pudhuzar, E. J. (1973). Multiple Regression in Behavioral Research. Holt, Rinehart & Winston: New York.
Klein, D. F. (1968). Diagnosis and pattern of reaction to drug treatment: clinically derived foundations. In Classification in Psychiatry and Psychopathology (ed. Katz, M. M., Cole, J. O. and Barton, W. E.), pp. 466482. DHEW No. (HSM) 72–9015. US Government Printing Office: Washington, D.C.
Klein, D. F. & Davis, J. (1969). Diagnosis and Treatment of Psychiatric Disorders. Williams & Wilkins: Baltimore.
Klein, D. F. & Rosen, B. (1973). Premorbid asocial adjustment and response to phenothiazine treatment among schizophrenic inpatients. Archives of General Psychiatry 29, 480485.
Kraepelin, E. (1919). Dementia Praecox and Paraphrenia. Livingstone: Edinburgh.
Lehmann, H. (1975). Psychopharmacological treatment of schizophrenia. Schizophrenia Bulletin 13, 2745.
Lorr, M., Klett, C. J. & McNair, D. M. (1963). Syndromes of Psychosis. Pergamon: London.
Marjot, D. H. (1969). Depression following fluphenazine treatment (letter). British Medical Journal i, 780.
Marsden, C. D. & Jenner, P. (1980). The pathophysiology of extrapyramidal side-effects of neuroleptic drugs. Psychological Medicine 10, 5572.
Mathysse, S. & Kidd, K. K. (1976). Estimating the genetic contribution in schizophrenia. American Journal of Psychiatry 131; 185191.
Mayr, E. (1972). Consequences of recent research findings. In Genetic Factors in ‘Schizophrenia’ (ed. Kaplan, A. R.), pp. 164173. C. C. Thomas: Springfield, Ill.
McGlashan, T. H. (1973). The Documentation of Clinical Psychotropic Drug Trials. DHEW No. (HSM) 73–9038. US Government Printing Office: Washington, D.C.
McGlashan, T. H. & Carpenter, W. T. (1976 a). Postpsychotic depression in schizophrenia. Archives of General Psychiatry 33, 231239.
McGlashan, T. H. & Carpenter, W. T. (1976 b). An investigation of the postpsychotic depressive syndrome. American Journal of Psychiatry 133, 1419.
McKinnon, B. L. (1977). Postpsychotic depression and the need for personal significance. American Journal of Psychiatry 134, 427429.
Meltzer, H. Y. (1979). Biology of schizophrenia subtypes. Schizophrenia Bulletin 5, 460479.
Mendlewicz, J., Fieve, R. R., Rainer, J. D. & Fleiss, J. L. (1972). Manic-depressive illness: a comparative study of patients with and without a family history. British Journal of Psychiatry 120, 523530.
Mendlewicz, J., Fleiss, J. L., Cataldo, M. & Rainer, J. D. (1975). Accuracy of the family history method in affective illness. Archives of General Psychiatry 32, 309314.
Mitsuda, H. (1967). Clinical genetics in psychiatry. In Clinical Genetics in Psychiatry (ed Mitsuda, H.), pp. 321. Igaku Shion: Tokyo.
Moore, K. E. & Kelly, P. H. (1978). Biochemical pharmacology of mesolimbic and mesocortical dopaminergic neurons. In Psychopharmacology: A Generation of Progress (ed. Lipton, M. A., DiMascio, A. and Killam, K. F.), pp. 221234. Raven Press: New York.
Murray, R. M. & Murphy, D. L. (1978). Drug response and psychiatric nosology. Psychological Medicine 8, 667681.
National Institute of Mental Health – Psychopharmacology Research Branch (1967). Differences in clinical effects of three phenothiazines in acute schizophrenia. Diseases of the Nervous System 28, 269383.
Ollerenshaw, D. P. (1973). The classification of the functional psychoses. British Journal of Psychiatry 122, 777788.
Overall, J. E. & Klett, C. J. (1972). Applied Multivariate Analysis. McGraw-Hill: New York.
Planansky, K. & Johnston, R. (1978). Depressive syndrome in schizophrenia. Acta psychiatrica scandinavica 57, 207218.
Pope, H. G. & Lipinski, J. F. (1978). Diagnosis in schizophrenia and manic-depressive illness. Archives of General Psychiatry 35, 811828.
Rieder, R. O. & Gershon, E. S. (1978). Genetic strategies in biological psychiatry. Archives of General Psychiatry 35, 866873.
Robins, A. H. (1976). Depression in patients with Parkinsonism. British Journal of Psychiatry 128, 141145.
Rosenthal, D. (1970). Genetic Theory and Abnormal Behavior. McGraw-Hill: New York.
Rosenthal, D. (1977). Searches for the mode of genetic transmission in schizophrenia. Schizophrenia Bulletin 5, 5986.
Roy, A. (1980). Depression in chronic paranoid schizophrenia. British Journal of Psychiatry 137, 138139.
Rüdin, E. (1916). Zur Vererbung end Neuentstehung der Dementia Praecox. Springer Verlag: Berlin.
Sachar, E. J., Mason, J. W. & Kolmer, H. A. (1963). Psychoencdocrine aspects of acute schizophrenic reactions. Psychosomatic Medicine 25, 510537.
Sachar, E. J., Kanter, S. S. & Buie, D. (1970). Psychoendocrinology of ego disintegration. American Journal of Psychiatry 126, 10671078.
Schulz, B. & Leonhard, K. (1940). Erbiologische-klinische Untersuchungen an Insegsamt 99 im Sinne Leonhards typische beziehungsweise atypischen Schizophrenien. Zentralblatt für die gesamte Neurologie und Psychiatrie 168, 587613.
Schwab, H. (1938). Die Katatonie auf Grund katamnestischer Untersuchungen. II. Die Erblichkeit der eigenlichen Katatonie. Zentralblatt für die gesamte Neurologie und Psychiatrie 163, 441506.
Shanfield, S., Tucker, G. J. & Harrow, M. (1970). The schizophrenic patient and depressive symptomatology. Journal of Nervous and Mental Disease 151, 203210.
Siever, L. J. & Gunderson, J. G. (1979), Genetic determinants of borderline conditions. Schizophrenia Bulletin 5, 268276.
Singh, M. M. (1976). Dysphoric response to neuroleptic treatment in schizophrenia and its prognostic significance. Diseases of the Nervous System 37, 191204.
Singh, M. M. & Kay, S. R. (1979). Dysphoric response to neuroleptic treatment in schizophrenia: its relationship to autonomic arousal and prognosis. Biological Psychiatry 14, 277294.
Slater, E. (1953). Psychotic and Neurotic Illnesses in Twins. HMSO: London
Slater, E. & Cowie, V. (1971). The Genetics of Mental Disorders. Oxford University Press: London.
Slater, E. & Roth, M. (1969). In Clinical Psychiatry (ed. Mayer-Gross, W., Slater, E. and Roth, M.), pp. 237341. Oxford University Press: London.
Snyder, S., Greenberg, D. & Yamamura, H. I. (1974). Antischizophrenic drugs and brain cholinergic receptors. Archives of General Psychiatry 31, 5861.
Spitzer, R. L., Endicott, J. & Robins, E. (1978). Research diagnostic criteria. Archives of General Psychiatry 35, 773782.
Tsuang, M. T. (1967). A study of pairs of sibs both hospitalized for mental disorders. British Journal of Psychiatry 113, 283300.
van Putten, T. & May, P. R. A. (1978). Akinetic depression in schizophrenia. Archives of General Psychiatry 35, 11011107.
Warburton, J. W. (1967). Depressive symptoms in Parkinson patients referred for thalamotomy. Journal of Neurology Neurosurgery and Psychiatry 30, 121128.
Winokur, G. (1978). Paranoid versus hebephrenic schizophrenia: a differentiation based on clinical and family (genetic) findings. In Biochemistry of Mental Disorders (ed. Usdin, E. and Mandell, A. J.), pp. 1126. Marcel Dekker: New York.
Winokur, G., Behar, D., Van Valkenberg, C. & Lowry, M. (1978). Is a familial definition of depression both feasible and valid? Journal of Nervous and Mental Disease 166, 764768.
Wyatt, R. J. (1976). Biochemistry and schizophrenia (Part IV). The neuroleptics – their mechanism of action: a review of the biochemical literature. Psychopharmacology Bulletin 12, 550.
Zerbin-Rudin, E. (1973). Genetic research and the theory of schizophrenia. In Annual Review of the Schizophrenic Syndrome (ed. Cancro, R.), pp. 302324. Brunner/Mazel: New York.
Zhislin, S. G. (1964). The changing symptomatology and evolution of psychoses in modern psychotropic medication. In Problems of Psychopharmacology (ed. Rohklin, L. L.), pp. 5160. Davey: New York.

Genetic factors in the response to neuroleptics in schizophrenia: a psychopharmacogenetic study

  • Joe Galdi (a1), Ronald O. Rieder (a1), David Silber (a1) and Roland R. Bonato (a1)

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed