Hostname: page-component-8448b6f56d-tj2md Total loading time: 0 Render date: 2024-04-24T09:30:45.710Z Has data issue: false hasContentIssue false
  • English
  • Français

The biochemical basis of relapse and drug response in schizophrenia: review and hypothesis

Published online by Cambridge University Press:  09 July 2009

Daniel P. Van Kammen
Daniel P. Van Kammen*
Affiliation:
Highland Drive VA Medical Center, US Department of Veterans Affairs; Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
*
1Address for correspondence: Professor Daniel P. van Kammen, Highland Drive VAMC, Pittsburgh, PA 15206, USA.
Get access Rights & Permissions [Opens in a new window]

Synopsis

This review of the literature suggests that antipsychotic drug response is determined by dopamine (DA) turnover and norepinephrine (NE) activity prior to treatment. The data suggest that NE modulates the DA system. Drug-free psychotic patients with relatively increased DA and NE activity, including release, are more likely to be treatment responsive, while patients who show evidence of enhanced DA and NE activity during treatment with antipsychotic drugs are likely to relapse soon after neuroleptic withdrawal. Basal release of DA and NE is decreased and associated with residual positive and negative symptoms. Improvement during neuroleptic treatment is associated with decreases in DA and NE phasic or stimulus induced release. The variable response to antipsychotic drugs is most likely to be a result of dysregulated DA and NE release, i.e. under state-dependent control, rather than evidence of a heterogeneous aetiology. Because catecholamines regulate gain, signal-to-noise ratio and gating in the brain, this model allows for environmental factors to interact with biochemical state and drug treatment. The author proposes that impaired homeostasis of NE and DA in schizophrenia causes instability in NE and DA neuronal firing and release, presumably related to mechanisms down-stream from the receptors, such as G proteins. This instability of catecholamine release may explain the observed variability in clinical states and drug response in schizophrenia.

Type
Original Articles
Information
Psychological Medicine , Volume 21 , Issue 4 , November 1991 , pp. 881 - 895
Copyright
Copyright © Cambridge University Press 1991

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

Abercrombie, E. D. & Zigmond, M. J. (1989). Partial injury to central noradrenergic neurons: reduction of tissue norepinephrine content is greater than reduction of extracellular norepinephrine measured by microdialysis. Journal of Neuroscience 9, 4062–4067.CrossRefGoogle ScholarPubMed
Ackenheil, M., Albus, M., Naber, D., Reinertshofer, T. & Müller-Spahn, F. (1986). Neuroleptic withdrawal in chronic schizophrenia. CT and endocrine variables are not valid predictors of psychopathological changes. International Journal of Neuroscience 31, 142.Google Scholar
Andén, N. E. & Grabowska, M. (1976). Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain. European Journal of Pharmacology 39, 275–282.CrossRefGoogle ScholarPubMed
Andreasen, N. C., Flaum, M., Swayze, V. W. II, Tyrrell, G. & Arndt, S. W. (1990). Positive and negative symptoms in schizophrenia: a critical appraisal. Archives of General Psychiatry 47, 615–621.CrossRefGoogle Scholar
Angrist, B. & van Kammen, D. P. (1984). CNS stimulants as tools in the study of schizophrenia. Trends in Neurosciences 7, 388–390.CrossRefGoogle Scholar
Angrist, B. M., Dathananthan, G., Wilk, S. & Gershon, S. (1973). Behavioural and biochemical effects of L-dopa in psychiatric patients. In Frontiers in Catecholamine Research (ed. Usdin, E., Kopin, I. J. an Barchas, J.), pp. 991–994. Pergamon Press: Oxford.CrossRefGoogle Scholar
Angrist, B., Rotrosen, J. & Gershon, S. (1980). Responses to apomorphine, amphetamine, and neuroleptics in schizophrenic subjects. Psychopharmacology 67, 31–38.CrossRefGoogle ScholarPubMed
Angrist, B., Peselow, E., Rotrosen, J. & Gershon, S. (1981). Relationships between responses to dopamine agonists: psychopathology, neuroleptic treatment response, and need for neuroleptic maintenance in schizophrenic subjects. In Recent Advances in Neuropsychopharmacology (ed. Angrist, B., Burrows, G. D., Lader, M., Lingjaerde, O., Sedvall, G. and Wheatly, D.), pp. 49–54. Pergamon Press: Oxford.CrossRefGoogle Scholar
Archer, T. (1982). The role of NE in learned behaviours: studies using DSP4. Scandinavian Journal of Psychology 1 (suppl.), 61–71.CrossRefGoogle Scholar
Bacopoulos, N. S., Spokes, E. G., Bird, E. D. & Roth, R. H. (1979). Antipsychotic drug action in schizophrenic patients: effect on cortical dopamine metabolism after long-term treatment. Science 205, 1405–1407.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Baumgartner, A., Gräf, K.-L., Kärten, I. & Meinhold, H. (1988). The hypothalamic–pituitary–thyroid axis in psychiatric patients and healthy subjects: part 1–4. Psychiatry Research 24, 271–332.CrossRefGoogle Scholar
Beasley, C. M., Magnusson, M. & Garver, D. L. (1988). TSH response to TRH and haloperidol response latency in psychoses. Biological Psychiatry 24, 423–431.CrossRefGoogle ScholarPubMed
Beaulieu, M. & Coyle, J. T. (1983). Postnatal development of aminergic projections to frontal cortex: effects of cortical lesions. Journal of Neuroscience Research 10, 351–361.CrossRefGoogle ScholarPubMed
Beckmann, H., Waldmeier, P., Lauber, J. & Gattaz, W. F. (1983). Phenylethylamine and monamine metabolites in CSF of schizophrenics: effects of neuroleptic treatment. Journal of Neural Transmission 57, 103–110.CrossRefGoogle Scholar
Bell, D. S. (1973). The experimental reproduction of amphetamine psychosis. Archives of General Psychiatry 29, 35–40.CrossRefGoogle ScholarPubMed
Besses, G. S., Burrow, G. N., Spaulding, S. W. & Donabedian, R. K. (1975). Dopamine infusion acutely inhibits the TSH and prolactin response to TRH. Journal of Endocrinology and Metabolism 41, 985–987.CrossRefGoogle ScholarPubMed
Bleuler, M. (1978). The Schizophrenic Disorders: Long-Term Patient and Family Studies. Yale University Press: New Haven.Google Scholar
Bowers, M. B. (1974). Central dopamine turnover in schizophrenic syndromes. Archives of General Psychiatry 31, 50–54.CrossRefGoogle ScholarPubMed
Bowers, M. B. (1988). Plasma monoamine metabolites in psychotic disorders. Archives of General Psychiatry 45, 595–596.CrossRefGoogle ScholarPubMed
Bowers, M. B., Swigar, M. E., Jatlow, P. I., Hoffman, F. & Goicoechea, N. (1986). Early neuroleptic response in psychotic men and women: correlation with plasma HVA and MHPG. Comprehensive Psychiatry 27, 181–185.CrossRefGoogle ScholarPubMed
Bowers, M. B., Swigar, M. E., Jatlow, P. I., Hoffman, F. J. & Goicoechea, N. (1987). Early neuroleptic response: clinical profiles and plasma catecholamine metabolites. Journal of Clinical Psychopharmacology 7, 83–86.CrossRefGoogle ScholarPubMed
Brown, W. A. & Herz, L. R. (1989). Response to neuroleptic drugs as a device for classifying schizophrenia. Schizophrenia Bulletin 15, 123–129.CrossRefGoogle ScholarPubMed
Brown, W. A. & Laughren, T. (1979). Low serum prolactin and early relapse following neuroleptic withdrawal. American Journal of Psychiatry 138, 237–239.Google Scholar
Brown, W. A. & Laughren, T. P. (1981). Tolerance to the prolactin-elevating effect of neuroleptics. Psychiatry Research 5, 317–322.CrossRefGoogle Scholar
Bunney, B. S. & DeRiemer, S. (1982). Effect of clonidine on dopaminergic neuron activity in the substantia nigra: possible indirect mediation by noradrenergic regulation of the serotonergic raphi system. Advances in Neurology 35, 99–104.Google Scholar
Cannon-Spoor, H. E., Potkin, S. G. & Wyatt, R. J. (1982). Measurement of premorbid adjustment in chronic schizophrenia. Schizophrenia Bulletin 8, 460–484.CrossRefGoogle ScholarPubMed
Carboni, E., Tanda, G. L., Fray, R. & Di Chiara, G. (1990). Blockade of the noradrenaline carrier increases extracellular dopamine concentrations in the prefrontal cortex: evidence that dopamine is taken in vivo by noradrenergic terminals. Journal of Neurochemistry 55, 1067–1070.CrossRefGoogle ScholarPubMed
Carlsson, A. (1978). Does dopamine have a role in schizophrenia? Biological Psychiatry 13, 3–21.Google ScholarPubMed
Carlsson, A. & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica 20, 140–144.CrossRefGoogle ScholarPubMed
Chang, W.-H., Chen, T. Y., Lee, C.-F., Hung, J.-C., Hu, W.-H. & Yeh, E.-K. (1988). Plasma homovanillic acid levels and subtyping of schizophrenia. Psychiatry Research 23, 239–244.CrossRefGoogle ScholarPubMed
Chang, W.-H., Chen, T.-Y., Lin, S.-K., Lung, F.-W., Lin, W.-L., Hu, W.-H. & Yeh, E.-K. (1990). Plasma catecholamine metabolites in schizophrenics: evidence for the two-subtype concept. Biological Psychiatry 27, 510–518.CrossRefGoogle ScholarPubMed
Ciompi, L. (1980). The natural history of schizophrenia in the long term. British Journal of Psychiatry 136, 413–420.CrossRefGoogle ScholarPubMed
Cleghorn, J. M., Brown, G. M., Brown, P. J., Kaplan, R. D., Dermer, S. W., MacCrimmon, D. J. & Mitton, J. (1983). Growth hormone responses to apomorphine HC1 in schizophrenic patients on drug holidays and at relapse. British Journal of Psychiatry 142, 482–488.CrossRefGoogle Scholar
Cohen, B. M. & Lipinski, J. F. (1986). In vivo potencies of antipsychotic drugs in blocking alphal noradrenergic and dopamine D2 receptors: implications for drug mechanisms of action. Life Sciences 39, 2571–2580.CrossRefGoogle Scholar
Connell, P. H. (1958). Amphetamine Psychosis, Maudsley Monograph Nr 5. Chapman and Hall: London.Google Scholar
Cooper, S. J., Leahey, W., Liddle, J. & King, D. J. (1990). The relationship between clinical and biochemical changes following neuroleptic treatment in schizophrenia. Schizophrenia Research 3, 261–267.CrossRefGoogle ScholarPubMed
Creese, I., Burt, D. R. & Snyder, S. H. (1976). Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192, 481–483.CrossRefGoogle ScholarPubMed
Crow, T. J. (1980). Molecular pathology of schizophrenia: more than one disease process? British Journal of Medicine 280, 66–68.CrossRefGoogle ScholarPubMed
Csernansky, J. G., Kaplan, J. & Hollister, L. E. (1985). Problems in classification of schizophrenics as neuroleptic responders and nonresponders. Journal of Nervous and Mental Disease 173, 325–331.CrossRefGoogle ScholarPubMed
Davidson, M., Keefe, R. S. E., Mohs, R. C., Siever, L. J., Losonczy, M. F., Horvath, T. B. & Davis, K. L. (1987). L-Dopa challenge and relapse in schizophrenia. American Journal of Psychiatry 144, 934–938.Google ScholarPubMed
Davidson, M. & Davis, K. L. (1988). A comparison of plasma homovanillic acid concentrations in schizophrenic patients and normal controls. Archives of General Psychiatry 45, 561–563.CrossRefGoogle ScholarPubMed
Davidson, M., Kahn, R. S., Warne, P., Powchick, P., Kaminsky, R., Apter, S., Japp, S. & Davis, K. L. (1991). Changes in plasma homovanillic acid concentrations in schizophrenic patients following neuroleptic discontinuation. Archives of General Psychiatry (in the press).Google ScholarPubMed
Davila, R., Manero, E., Zumarraga, M., Andia, I., Schweitzer, J. W. & Friedhoff, A. J. (1988). Plasma homovanillic acid as a predictor of response to neuroleptics. Archives of General Psychiatry 45, 564–567.CrossRefGoogle ScholarPubMed
Davis, K. L., Davidson, M., Mohs, R. C., Kendler, K. S., Davis, B. M., Johns, C. A., DeNigris, Y. & Horvath, T. B. (1985). Plasma homovanillic acid concentration and the severity of schizophrenic illness. Science 227, 1601–1602.CrossRefGoogle ScholarPubMed
Delini, A. & Hunn, C. (1990). Effects of single and repeated treatment with antidepressants on apomorphine-induced yawning in the rat: the implications of α1 adrenergic mechanisms in the D2 receptor function. Psychopharmacology 101, 62–66.CrossRefGoogle Scholar
DeLisi, L. E. & Dauphinais, D. (1989). Neuroleptic responsiveness in siblings concordant for schizophrenia. Archives of General Psychiatry 46, 477.CrossRefGoogle ScholarPubMed
Dencker, S. J., Malm, U. & Lepp, M. (1986). Schizophrenic relapse after drug withdrawal is predictable. Acta Psychiatrica Scandinavica 73, 181–185.CrossRefGoogle ScholarPubMed
Deutch, A. Y., Clark, W. A. & Roth, R. H. (1990). Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress. Brain Research 521, 311–315.CrossRefGoogle ScholarPubMed
Dickinson, S. L., Gadie, B. & Tulloch, I. F. (1988). Alpha1 and alpha2 adrenoreceptor antagonists differentially influence locomotor and stereotyped behaviour induced by D-amphetamine and apomorphine in the rat. Psychopharmacology 96, 521–527.CrossRefGoogle Scholar
Dinan, T. G. & Aston-Jones, G. (1985). Chronic haloperidol inactivates brain noradrenergic neurons. Brain Research 325, 385–388.CrossRefGoogle ScholarPubMed
Docherty, J. P., van Kammen, D. P., Siris, S. G. & Marder, S. R. (1978). Stages of onset of schizophrenic psychosis. American Journal of Psychiatry 135, 420–426.Google ScholarPubMed
Elsworth, J. D., Leahy, D. J., Roth, R. H. & Redmond, D. E. (1987). Homovanillic acid concentrations in brain, CSF and plasma as indicators of central dopamine function in primates. Journal of Neural Transmission 68, 51–62.CrossRefGoogle ScholarPubMed
Farde, L., Pauli, S., Hall, H., Eriksson, L., Halldin, C., Högberg, T., Nilsson, L., Sjögren, I. & Stone-Elander, S. (1986). Stereoselective binding of 11C-raclopride in living human brain – a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology 94, 471–478.CrossRefGoogle Scholar
Foote, S. L., Bloom, F. E. & Aston-Jones, G. (1983). Nucleus locus coeruleus: new evidence of anatomical and physiological specificity. Physiology Review 63, 844–914.CrossRefGoogle ScholarPubMed
Garcia, A., Galinowski, A., Guicheney, P., Mignot, E., Loo, H. & Meyer, P. (1989). Free and conjugated plasma homovanillic acid in schizophrenic patients. Biological Psychiatry 26, 87–96.CrossRefGoogle ScholarPubMed
Garver, D. L., Zemlan, F., Hirschowitz, J. Hitzemann, R. Mavroidis, M. L. (1984). Dopamine and non-dopamine psychoses. Psychopharmacology 84, 138–140.CrossRefGoogle ScholarPubMed
Garver, D. L., Kelly, K., Fried, K. A., Magnusson, M. & Hirschowitz, J. (1988). Drug response patterns as a basis of nosology for the mood-incongruent psychoses (the schizophrenias). Psychological Medicine 18, 1–13.CrossRefGoogle ScholarPubMed
Gattaz, W. F., Riederer, P., Reynolds, G. P., Gattaz, D. & Beckmann, H. (1983). Dopamine and norpinephrine in the cerebrospinal fluid of schizophrenic patients. Psychiatry Research 8, 243–250.CrossRefGoogle Scholar
Gilman, A. G. (1987). G proteins: transducers of receptor-generated signals. Annual Review of Biochemistry 56, 615–649.CrossRefGoogle ScholarPubMed
Glowinski, J., Hervé, D. & Tassin, J. P. (1988). Heterologous regulation of receptors on target cells of dopamine neurons in the prefrontal cortex, nucleus accumbens and striatum. In The Mesocorticolimbic Dopamine System. (ed. Kalivas, P. W. and Nemeroff, C. W.), Annals of the New York Academy of Sciences 137, 112–123.Google Scholar
Goetz, K. L. & van Kammen, D. P. (1986). Computerized axial tomography scans and subtypes of schizophrenia. Journal of Nervous and Mental Disease 174, 31–41.CrossRefGoogle ScholarPubMed
Goldman-Rakic, P. S. (1987). Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In Handbook of Physiology – The Nervous System V (ed. Plum, E.), pp. 373–417. American Physiological Society: Betheseda, MD.Google Scholar
Grace, A. A. & Bunney, B. S. (1980). Nigral dopamine neurons: intracellular recording and identification with L-dopa injection and histofluorescence. Science 210, 654–656.CrossRefGoogle ScholarPubMed
Grenhoff, J. & Svensson, T. H. (1988). Clonidine regularizes substantia nigra dopamine cell firing. Life Sciences 43, 2003–2009.CrossRefGoogle Scholar
Hallman, H., Sundstrom, E. & Jonsson, G. (1982). Effects of the NE neurotoxin DSP-4 on monoamine neurons and their transmitter turnover in rat CNS. Journal of Neural Transmission 60, 89–102.CrossRefGoogle Scholar
Harding, C. & Strauss, J. S. (1985). The course of schizophrenia: an evolving concept. Controversies in Schizophrenia: Changes and Constancies. (ed. Alpert, M.), pp. 339–353. Guilford Press: New York.Google Scholar
Hervé, S. & Le Moal, M. (1988). Mesencephalic dopaminergic neurons: role in the general economy of the brain. Annals of the New York Academy of Sciences 537 235–253.Google Scholar
Herz, M. I. & Melville, C. (1980). Relapse in schizophrenia. American Journal of Psychiatry 137, 801–805.Google ScholarPubMed
Hess, E. J., Bracha, S., Kleinman, J. E. & Creese, I. (1987). Dopamine receptor subtype imbalance in schizophrenia. Life Sciences 40, 1487–1497.CrossRefGoogle ScholarPubMed
Hogarty, G. E., Goldberg, S. C., Schooler, N. R. & Ulrich, R. F. (1974). Drug and sociotherapy in the aftercare of schizophrenic patients. II. Two-year relapse rates. Archives of General Psychiatry 31, 603–608.CrossRefGoogle ScholarPubMed
Hornykiewicz, O. (1982). Brain catecholamine in schizophrenia – a good case for noradrenalin. Nature 299, 484–486.CrossRefGoogle Scholar
Huber, G., Gross, G., Schuttler, R. & Linz, M. (1980). Longitudinal studies of schizophrenic patients. Schizophrenia Bulletin 6, 592–605.CrossRefGoogle ScholarPubMed
Ionesco, E. (1960). Rhinoceros and Other Plays. Grove Press: New York.Google Scholar
Iversen, L. L. (1975). Dopamine receptors in the brain. Science 188, 1084–1089.CrossRefGoogle ScholarPubMed
Janicak, P. G., Javaid, J. I., Sharma, R. P., Comaty, J. E., Peterson, J. & Davis, J. M. (1989). Trifluoperazine plasma levels and clinical response. Journal of Clinical Psychopharmacology 9, 340–346.CrossRefGoogle ScholarPubMed
Janowsky, D. S. & Davis, J. M. (1976). Methylphenidate, dextroamphetamine, and levamphetamine: effects on schizophrenic symptoms. Archives of General Psychiatry 33, 304–308.CrossRefGoogle ScholarPubMed
Janowsky, D. S., El-Yousef, K., Davis, J. M. & Sekerke, H. J. (1973). Provocation of schizophrenic symptoms by intravenous administration of methylphenidate. Archives of General Psychiatry 28, 185–191.CrossRefGoogle ScholarPubMed
Janssen, P. A. & van Bever, W. F. (1978). Preclinical psychopharmacology of neuroleptics. In Principles of Pharmacology (ed. Clark, W. G. and Del Guidice, J.), pp. 279–295. Academic Press: New York.Google Scholar
Kafka, M. S. & van Kammen, D. P. (1983). Alpha-adrenergic receptor function in schizophrenia: receptor number, cyclic adenosine monophosphate production, adenylate cyclase activity, and effects of drugs. Archives of General Psychiatry 40, 264–270.CrossRefGoogle ScholarPubMed
Kaufmann, C. A., Jeste, D. V., Shelton, R. C., Linnoila, M., Kafka, M. S. & Wyatt, R. J. (1986). Noradrenergic and neuroradiological abnormalities in tardive dyskinesia. Biological Psychiatry 21, 799–812.CrossRefGoogle ScholarPubMed
Kemali, D., Delvecchio, M. & Maj, M. (1982). Increased nor-adrenaline levels in CSF and plasma of schizophrenic patients. Biological Psychiatry 17, 711–717.Google ScholarPubMed
King, R., Raese, J. D. & Barchas, J. D. (1981). Catastrophe theory of dopaminergic transmission: a revised dopamine hypothesis of schizophrenia. Journal of Theoretical Biology 92, 373–400.CrossRefGoogle ScholarPubMed
King, R, Barchas, J. D. & Huberman, B. A. (1984). Chaotic behavior in dopamine neurodynamics. Proceedings of the National Academy of Sciences, USA 8, 1244–1247.CrossRefGoogle Scholar
Kirch, D. G., Jaskiw, G., Linnoila, M., Weinberger, D. R. & Wyatt, R. J. (1988). Plasma amine metabolites before and after withdrawal from neuroleptic treatment in chronic schizophrenic inpatients. Psychiatry Research 25, 233–242.CrossRefGoogle ScholarPubMed
Klein, D. F. & Davis, J. M. (1969). Diagnosis and Drug Treatment of Psychiatric Disorders. Williams and Wilkins: Baltimore.Google Scholar
Kolakowska, T., Wiles, D. H., McNeilly, A. S. & Gelder, M. G. (1975). Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients. Psychological Medicine 5, 214–216.CrossRefGoogle ScholarPubMed
Kopin, I. J., Bankiewicz, K. S. & Harvey-White, J. (1988). Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP. Neuropsychopharmacology 1, 119–125.CrossRefGoogle ScholarPubMed
Lake, C. R., Sternberg, D. E., van Kammen, D. P., Ballenger, J. C., Ziegler, M. G., Post, R. M., Kopin, I. J. & Bunney, W. E. Jr. (1980). Schizophrenia: elevated cerebrospinal fluid norepinephrine. Science 207, 331–333.CrossRefGoogle ScholarPubMed
Lal, S., Nair, N. P. V., Thavundayil, J. X., Monks, R. C. & Guyda, H. (1983). Clonidine-induced growth hormone secretion in chronic schizophrenia. Acta Psychiatrica Scandinavica 68, 82–88.CrossRefGoogle ScholarPubMed
Langer, A. Z. (1981). Presynaptic regulation of the release of catecholamines. Pharmacological Reviews 32, 337–362.Google Scholar
Langer, G., Koinig, G., Hatzinger, R., Schonbeck, G., Resch, F., Aschauer, H., Keshavan, M. S. & Sieghart, W. (1986). Response of thyrotropin to thyrotropin-releasing hormone as predictor of treatment outcome. Archives of General Psychiatry 43, 861–868.CrossRefGoogle ScholarPubMed
Leckman, J. D., Cohen, D. J., Shaywitz, B. A., Caparula, B. K., Heninger, G. R. & Bowers, M. B. (1980). CSF monoamine metabolites in child and adult psychiatric patients. Archives of General Psychiatry 37, 677–681.CrossRefGoogle ScholarPubMed
Leff, J., Kuipers, L., Berkowitz, R., Vaughn, C. & Sturgeon, D. (1983). Life events, relatives' expressed emotion and maintenance neuroleptics in schizophrenic relapse. Psychological Medicine 13, 799–806.CrossRefGoogle ScholarPubMed
Lieberman, J. A., Kane, J. M., Gadaleta, D., Brenner, R., Lesser, M. S. & Kinon, B. (1984). Methylphenidate challenge as a predictor of relapse in schizophrenia. American Journal of Psychiatry 141, 633–638.Google ScholarPubMed
Lieberman, J. A., Kane, J. M., Gadaleta, D., Ramos-Lorenzi, J., Bergmann, K., Wegner, J. & Novacenko, H. (1985). Methylphenidate challenge tests and course of schizophrenia. Psychopharmacology Bulletin 21, 123–129.Google ScholarPubMed
Lieberman, J. A., Kane, J. M., Sarantakos, S., Gadaleta, D., Woerner, M., Alvir, J. & Ramos-Lorenzi, J. (1987). Prediction of relapse in schizophrenia. Archives of General Psychiatry 44, 597–603.CrossRefGoogle ScholarPubMed
Lohr, J. B. & Jeste, D. V. (1988). Locus coeruleus morphometry in aging and schizophrenia. Acta Psychiatrica Scandinavica 77, 689–697.CrossRefGoogle ScholarPubMed
Loosen, P. T. (1985). The TRH-induced TSH response in psychiatric patients: a possible neuroendocrine marker. Psychoneuroendocrinology 10, 237–260.CrossRefGoogle ScholarPubMed
Loosen, P. T. & Prange, A. J. (1982). Serum thyrotropin-releasing hormone in psychiatric patients: a review. American Journal of Psychiatry 139, 405–416.Google ScholarPubMed
Maas, J. W., Contreras, S. A., Seleshi, E. & Bowden, C. L. (1988). Dopamine metabolism and disposition in schizophrenic patients. Archives of General Psychiatry 45, 553–559.CrossRefGoogle ScholarPubMed
Malas, K. L., van Kammen, D. P., DeFraites, E. A., Brown, G. M. & Gold, P. W. (1983). Platelet monoamine oxidase and the growth hormone response to apomorphine in schizophrenia. Biological Psychiatry 18, 255–259.Google ScholarPubMed
Marder, S. P., van Kammen, D. P. & Bunney, W. E. Jr. (1979). Predicting drug-free improvement from schizophrenic psychosis. Archives of General Psychiatry 36, 1030–1085.CrossRefGoogle ScholarPubMed
Marwaha, J., Hoffer, B. J., Geller, H. M. & Freedman, R. (1981). Electrophysiologic interactions of antipsychotic drugs with central noradrenergic pathways. Psychopharmacology 73, 126–133.CrossRefGoogle ScholarPubMed
May, P. R. A., Van Putten, T. & Tale, C. (1980). Predicting outcome of antipsychotic drug treatment from early response. American Journal of Psychiatry 137, 1088–1089.Google ScholarPubMed
Meller, E., Bordi, F. & Bohmaker, K. (1989). Behavioural recovery after irreversible inactivation of D1 and D2 dopamine receptors. Life Sciences 44, 1019–1026.CrossRefGoogle Scholar
Meltzer, H. Y. (1984). Dopamine and negative symptoms in schizophrenia: critique of the type I-II hypothesis. In Controversies in Schizophrenia, Changes and Constancies (ed. Alpert, M.), pp. 110–144. Guilford Press: New York.Google Scholar
Meltzer, H. Y. & Fang, V. S. (1976). The effect of neuroleptics on serum prolactin in schizophrenic patients. Archives of General Psychiatry 33, 279–286.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Kolakowska, T., Fang, V. S., Fogg, L., Robertson, A., Lewine, R., Strahilevitz, M. & Busch, D. (1984). Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Archives of General Psychiatry 41, 512–519.CrossRefGoogle ScholarPubMed
Memo, M., Kleinman, J. E. & Hanbauer, I. (1983). Coupling of dopamine D1 recognition sites with adenylate cyclase in nuclei accumbens and caudatus of schizophrenics. Science 221, 1304–1307.CrossRefGoogle ScholarPubMed
Mooney, J. J., Schatzberg, A. F., Cole, J. O., Kizuka, P. P., Salomon, M., Lerbinger, J., Pappalardo, K. M., Gerson, B. & Schildkraut, J. J. (1988). Rapid antidepressant response to alprazolam in depressed patients with high catecholamine output and heterologous desensitization of platelet adenylate cyclase. Biological Psychiatry 23, 543–559.CrossRefGoogle ScholarPubMed
Morley, J. (1981). Neuroendocrine control of thyrotropin secretion. Endocrinological Review 2, 396–436.CrossRefGoogle ScholarPubMed
Naber, D., Albus, M., Burke, H., Müller-Spahn, F., Munch, U., Reinertshofer, T., Ackenheil, M. & Wissmann, J. (1985). Neuroleptic withdrawal in chronic schizophrenica: CT and endocrine variables relating to psychopathology. Psychiatry Research 16, 207–219.CrossRefGoogle ScholarPubMed
Nakamura, S. & Sakaguchi, T. (1990). Development and plasticity of the locus coeruleus: a review of recent physiological and pharmacological experimentation. Progress in Neurobiology 34, 505–526.CrossRefGoogle ScholarPubMed
Nasrallah, H. A., Kuperman, S., Hamra, B. J., McCallay, W. M. & Whitters, M. (1983). Clinical differences between schizophrenic patients with and without large cerebral ventricles. Journal of Clinical Psychiatry 44, 407–409.Google ScholarPubMed
Ornstein, K., Milon, H., McRae-Degueurce, A., Alvarez, C., Berger, B. & Wurzner, H. P. (1987). Biochemical and radioautographic evidence for dopaminergic afferents of the locus coeruleus originating in the ventral tegmental area. Journal of Neural Transmission 70, 183–191.CrossRefGoogle ScholarPubMed
Pandey, G. N., Janicak, P. G., Javaid, J. I. & Davis, J. M. (1989). Increased 3H-clonidine binding in the platelets of patients with depressive and schizophrenic disorders. Psychiatry Research 28, 83–88.CrossRefGoogle ScholarPubMed
Peroutka, S. J., U'Prichard, D. C., Greenberg, D. A. & Snyder, S. H. (1977). Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology 16, 549–556.CrossRefGoogle ScholarPubMed
Pohl, B. & Winokur, G. (1983). The micropsychopathology of hebephrenic-catatonic schizophrenia. Journal of Nervous and Mental Disease 171, 296–300.Google Scholar
Pickar, D., Labarca, R., Linnoila, M., Ray, A., Hommer, D., Everett, D. & Paul, S. M. (1984). Neuroleptic-induced decrease in plasma homovanillic acid and antipsychotic activity in schizophrenic patients. Science 225, 954–957.CrossRefGoogle ScholarPubMed
Post, R. M. & Goodwin, F. K. (1974). Time dependent effects of phenothiazines on dopamine turnover in psychiatric patients. Science 190, 488–489.CrossRefGoogle Scholar
Post, R. M., Fink, E., Carpenter, W. T. & Goodwin, F. K. (1975). Cerebrospinal fluid amine metabolites in acute schizophrenia. Archives of General Psychiatry 32, 1063–1069.CrossRefGoogle ScholarPubMed
Pycock, C. J., Kerwin, R. W. & Carter, C. J. (1980). Effect of cortical dopamine terminals on subcortical dopamine in rats. Nature 286, 74–77.CrossRefGoogle ScholarPubMed
Rakic, P. (1988). Specifics of cerebral cortical areas. Science 241, 170–176.CrossRefGoogle ScholarPubMed
Rao, M. L., Gross, G. & Huber, G. (1984). Altered interrelationship of dopamine, prolactin, thyrotropin, and thyroid hormone in schizophrenia patients. European Archives of Psychiatric and Neurological Sciences 234, 8–12.CrossRefGoogle Scholar
Reichlin, S. (1978). Regulation of the hypophysiotropic secretions of the brain. Archives of Internal Medicine 135, 1350–1361.CrossRefGoogle Scholar
Reisine, T. D., Chesselet, M. F., Lubetzki, C., Cheramy, A. & Glowinski, J. (1982). Striatel beta-adrenergic receptors regulate dopamine release. Society of Neuroscience, Abstracts 8, 526.Google Scholar
Reubenstein, M., Schinder, A. F., Gershanik, O. & Stefano, F. J. E. (1989). Positive interaction between alpha-1 adrenergic and dopamine-2 receptors in locomotor activity of normo and supersensitive mice. Life Sciences 44, 337–346.CrossRefGoogle Scholar
Roth, R. H., Tam, S.-Y., Ida, Y., Yang, J.-X. & Deutch, A. Y. (1988). Stress and the mesocorticolimbic dopamine systems. In The Mesocorticolimbic Dopamine System (ed. Kalivas, P. W. and Nemeroff, C. B.), Annals of the New York Academy of Science 537, 138–147.Google Scholar
Rubin, R. T. (1987). Prolactin and schizophrenia. In Psychopharmacology, The Third Generation of Progress (ed. Meltzer, H. Y.), pp. 803–808. Raven Press: New York.Google Scholar
Sato, M., Chen, C. C., Akiyama, K. & Otsuki, S. (1983). Acute exacerbation of paranoid psychotic state after long-term abstinence in patients with previous methamphetamine psychosis. Biological Psychiatry 18, 429–440.Google ScholarPubMed
Scheinin, H. & Virtanen, R. (1986). Effects of yohimbine and idazoxan on monoamine metabolites in rat cerebrospinal fluid. Life Sciences 39, 1439–1446.CrossRefGoogle ScholarPubMed
Schulz, S. C., Sinicrope, P., Kishore, P. & Friedel, R. O. (1983). Treatment response and ventricular brain enlargement in young schizophrenic patients. Psychopharmacology Bulletin 19, 510–512.Google ScholarPubMed
Sedvall, G., Alfredsson, G., Bjerkenstedt, L., Eneroth, P., Fryo, B., Harnryd, C. & Wode-Helgodt, B. (1976). Central biochemical correlates to antipsychotic drug action in man. In The Impact of Biology on Modern Psychiatry (ed. Gershon, E. S., Belmaker, R. H., Kety, S. S. and Rosenbaum, M.), pp. 41–45. Plenum Publishing Corporation: New York.Google Scholar
Seeman, P. (1990). Multiple D2 dopamine receptors. Clinical Neuropharmacology 13, suppl. 2, 124–125.Google Scholar
Seeman, P. & Lee, T. (1975). Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219.CrossRefGoogle ScholarPubMed
Seeman, P., Lee, T., Chau-Wong, M. & Wong, K. (1976). Antipsychotic drug doses and neuroleptic dopamine receptors. Nature 261, 717–719.CrossRefGoogle ScholarPubMed
Seeman, P., Bzowej, N. H., Guan, H. C., Bergeron, C., Reynolds, G. P., Bird, E. D., Riederer, P., Jellinger, K. & Tourtellotte, W. W. (1987). Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's Parkinson's and Huntington's diseases. Neuropsychopharmacology 1, 5–15.CrossRefGoogle ScholarPubMed
Seeman, P., Niznik, H. B., Guan, H.-C., Booth, G. & Ulpian, C. (1989). Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. Proceedings of the National Academy of Sciences, USA 86, 10156–10160.CrossRefGoogle ScholarPubMed
Servan-Schreiber, D., Printz, H. & Cohen, J. D. (1990). A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. Science 249, 892–895.CrossRefGoogle ScholarPubMed
Shelton, R. C., Karson, C. N., Doran, A. R., Pickar, D., Bigelow, L. B. & Weinberger, D. R. (1988). Cerebral structural pathology in schizophrenia: evidence for a selective prefrontal cortical deficit. American Journal of Psychiatry 145, 154–163.Google Scholar
Shostak, M., Perel, J. M., Stiller, R. L., Wyman, W. & Curran, S. (1987). Plasma haloperidol and clinical response: a role for reduced haloperidol in antipsychotic activity? Journal of Clinical Psychopharmacology 7, 394–400.CrossRefGoogle ScholarPubMed
Siris, S. G., van Kammen, D. P., DeFraites, E. G., Siris, E. S., Alexander, P. E., Docherty, J. P., Heykants, J. & Bunney, W. E. Jr. (1978). Serum prolactin and antipsychotic responses to pimozide in schizophrenia. Psychopharmacology Bulletin 14, 11–14.Google ScholarPubMed
Snyder, S. H. & Largent, B. L. (1989). Receptor mechanisms in antipsychotic drug action: focus on sigma receptors. Journal of Neuropsychiatry 1, 7–15.Google ScholarPubMed
Sokoloff, P., Giros, B., Martes, M.-P., Bouthenet, M.-L. & Schwartz, J.-C. (1990). Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347, 146–151.CrossRefGoogle ScholarPubMed
Sternberg, D. E., van Kammen, D. P., Lake, C. R., Ballenger, J. C., Marder, S. R. & Bunney, W. E. Jr. (1981). The effect of pimozide on CSF norepinephrine in schizophrenia. American Journal of Psychiatry 138, 1045–1051.Google ScholarPubMed
Sternberg, D. E., van Kammen, D. P., Lerner, P. & Bunney, W. E. Jr. (1982 a). Schizophrenia: dopamine beta-hydroxylase activity and treatment response. Science 216, 1423–1425.CrossRefGoogle ScholarPubMed
Sternberg, D. E., Charney, D. S., Heninger, G. R., Leckman, J. F., Hafstad, K. M. & Landis, H. (1982 b). Impaired presynaptic regulation in schizophrenia: effects of clonidine in schizophrenic patients and normal controls. Archives of General Psychiatry 39, 285–289.CrossRefGoogle ScholarPubMed
Sternberg, D. E., van Kammen, D. P., Lerner, P., Ballenger, J. C., Marder, S. R., Prost, R. M. & Bunney, W. E. Jr. (1983). CSF dopamine beta-hydroxylase in schizophrenia. Archives of General Psychiatry 40, 743–747.CrossRefGoogle ScholarPubMed
Straus, J. S., Hafez, H., Lieberman, P. & Harding, C. M. (1985). The course of psychiatric disorder. III. Longitudinal principles. American Journal of Psychiatry 142, 289–296.Google Scholar
Svensson, T. H. (1987). Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in the brain: putative implications for psychiatry and psychopharmacology. Psychopharmacology 92, 1–7.CrossRefGoogle ScholarPubMed
Swerdlow, N. R. & Koob, G. F. (1989). Norepinephrine stimulates behavioral activation in rats following depletion of nucleus accumbens dopamine. Pharmacology, Biochemistry and Behavior 33, 595–599.CrossRefGoogle ScholarPubMed
Tamminga, C. A., Schaffer, M. H., Smith, R. C. & Davis, J. M. (1978). Schizophrenic symptoms improve with apomorphine. Science 200, 567–568.CrossRefGoogle ScholarPubMed
Tassin, J. P., Hervé, D., Trovero, F., Blanc, G. & Glowinski, J. (1989). Interactions between noradrenergic and dopaminergic neurons projecting to the rat prefrontal cortex. Scientific Proceedings ACNP, p. 52.Google Scholar
Tatetsu, S. (1976). Schizophrenia and methamphetamine psychosis: histopathological comparison. In World Issues in the Problems of Schizophrenia Psychoses (ed. Fukuda, T. and Mitsuda, H.), pp. 109–114. Igaku-Shoin: New York.Google Scholar
van der Heyden, P., Ebinger, G. & Kanare, L. (1986). Vauquelin, epinephrine and norepinephrine stimulation of adenylate cyclase in bovine retina homogenate: evidence for interaction with the D1 receptor. Life Sciences 38, 1221–1228.CrossRefGoogle Scholar
van der Velde, C. D. (1976). Variability in schizophrenia. Archives of General Psychiatry 33, 489–496.CrossRefGoogle ScholarPubMed
van Kammen, D. P. (1980). Maintenance therapy: indications, guidelines and relapse rates. In Halperidol Update: 1958–1980 (ed. Ayd, F. J.), pp. 127–140. Medical Publication: Baltimore.Google Scholar
van Kammen, D. P. & Antelman, S. (1984). Impaired noradrenergic transmission in schizophrenia? A minireview. Life Sciences 34, 1403–1413.CrossRefGoogle Scholar
van Kammen, D. P. & Gelernter, J. (1987). Biochemical instability in schizophrenia. I. The norepinephrine system. In Psychopharmacology, the Third Generation of Progress (ed. Meltzer, H. Y.), pp. 745–751. Raven Press: New York.Google Scholar
van Kammen, D. P. & Kelley, M. E. (1991). Dopamine and norepinephrine activity in schizophrenia: an integrative perspective. Schizophrenia Research 4, 173–191.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Malas, K. L., Sternberg, D. E., Murphy, D. L., Lerner, P., Lake, C. R., Dalton, L. A. & Bunney, W. E. (1981). Platelet MAO and clinical variables in schizophrenia: inter-relationships with spinal fluid NE and NBH. Psychopharmacology Bulletin 17, 207–209.Google Scholar
van Kammen, D. P., Bunney, W. E. Jr., Docherty, J. P., Marder, S. R., Ebert, M. H., Rosenblatt, J. E. & Rayner, J. N. (1982 a). Damphetamine-induced heterogeneous changes in psychotic behavior in schizophrenia. American Journal of Psychiatry 139, 991–997.Google ScholarPubMed
van Kammen, D. P., Docherty, J. P. & Bunney, W. E. Jr. (1982 b). Prediction of early relapse after pimozide discontinuation by response to D-amphetamine during pimozide treatment. Biological Psychiatry 17, 233–242.Google ScholarPubMed
van Kammen, D. P., Docherty, J. P., Marder, S. R., Schulz, S. C., Dalton, L. & Bunney, W. E. Jr. (1982 c). Antipsychotic effects of pimozide in schizophrenia. Treatment response prediction with acute dextroamphetamine response. Archives of General Psychiatry 39, 261–266.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Docherty, J. P., Marder, S. R., Rayner, J. N. & Bunney, W. E. Jr. (1982 d). Long-term pimozide pretreatment differentially affects behavioral responses to dextroamphetamine in schizophrenia. Archives of General Psychiatry 39, 275–281.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Mann, L. S., Sternberg, D. E., Scheinin, M., Ninan, P. T., Marder, S. R., van Kammen, W. B., Rieder, R. O. & Linnoila, M. (1983). Dopamine-beta-hydroxylase activity and homovanillic acid in spinal fluid of schizophrenics with brain atrophy. Science 220, 974–977.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Rosen, J., Peters, J., Fields, R. & van Kammen, W. B. (1985). Are there state-dependent markers in schizophrenia? Psychopharmacology Bulletin 21, 497–502.Google ScholarPubMed
van Kammen, D. P., van Kammen, W. B., Mann, L. S., Seppala, T. & Linnoila, M. (1986). Dopamine metabolism in the cerebrospinal fluid of drug-free schizophrenic patients with and without cortical atrophy. Archives of General Psychiatry 43, 978–983.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Peters, J. L., Rosen, J., van Kammen, W. B., McAdam, D. & Linnoila, M. (1989 a). Clonidine treatment of schizophrenia: can we predict treatment response? Psychiatry Research 27, 297–311.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Peters, J., van Kammen, W. B., Nugent, A., Goetz, K. L., Yao, J. & Linnoila, M. (1989 b). CSF norepinephrine in schizophrenia is elevated prior to relapse after haloperidol withdrawal. Biological Psychiatry 26, 176–188.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Peters, J., Yao, J., van Kammen, W. B. & Shaw, D. (1990 a). Norepinephrine and relapse in chronic schizophrenia: negative symptoms revisited. Archives of General Psychiatry 47, 161–168.CrossRefGoogle ScholarPubMed
van Kammen, D. P., Peters, J., Yao, J., McAdam, D., Mouton, A. & Breeding, W. (1990 b). Prediction of relapse following neuroleptic withdrawal: the role of noradrenaline. Clinical Neuropharmacology 13, suppl. 2, 432–433.Google Scholar
van Kammen, D. P., Mouton, A., Kelley, M., Breeding, W. & Peters, J. (1991). Explorations of dopamine and noradrenaline activity and negative symptoms in schizophrenia: concepts and controversies. In Negative versus Positive Schizophrenia (ed. Marneros, A., Andreasen, N. C. and Tusang, M.). Springer-Verlag: Berlin. (In the press.)Google Scholar
van Praag, H. M. & Korf, J. (1975). Neuroleptics, catecholamines, and psychoses: a study of their interrelations. American Journal of Psychiatry 136, 593–597.Google Scholar
van Putten, T. & May, P. R. A. (1978). Subjective response as a predictor of outcome in pharmacotherapy. Archives of General Psychiatry 35, 477–480.CrossRefGoogle ScholarPubMed
van Putten, T., Marder, S. R. & Mintz, J. (1990 a). A controlled dose comparison of haloperidol in newly admitted schizophrenic patients. Archives of General Psychiatry 47, 754–758.CrossRefGoogle ScholarPubMed
van Putten, T., Marder, S. R., Wirshing, W. C. et al. (1990 b). The clinical significance of a plasma haloperidol and fluphenazine level. Clinical Neuropharmacology 13, suppl. 2, 430–431.Google Scholar
van Rossum, J. M. (1966). The significance of dopamine-receptor blockade for the mechanism of action of neuroleptic drugs. Archives of Internal Pharmacodynamics 160, 492–494.Google ScholarPubMed
Vita, A., Sacchetti, E., Valvassori, G. & Cazzullo, C. L. (1988). Brain morphology in schizophrenia: a 2- to 5-year CT scan follow-up study. Acta Psychiatrica Scandinavica 78, 618–621.CrossRefGoogle ScholarPubMed
Weinberger, D. R. (1987). Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry 44, 660–669.CrossRefGoogle ScholarPubMed
Weinberger, D. R., Bigelow, L. B., Kleinman, J. E., Klein, S. T., Rosenblatt, J. E. & Wyatt, R. J. (1980). Cerebral ventricular enlargement in chronic schizophrenia. An association with poor response to treatment. Archives of General Psychiatry 37, 11–13.CrossRefGoogle ScholarPubMed
Westerink, B. H. C., van der Heyden, J. A. M. & Korf, J. (1978). Enhanced dopamine metabolism after small lesions in the midbrain of the rat. Life Sciences 22, 749–756.CrossRefGoogle ScholarPubMed
White, F. J. & Wang, R. Y. (1983). Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 221, 1054–1057.CrossRefGoogle ScholarPubMed
Wolkin, A., Brodie, J. D., Barouche, F., Rotrosen, J., Wolf, A. P., Smith, M., Fowler, J. & Cooper, T. B. (1988). Dopamine receptor occupancy and plasma haloperidol levels. Archives of General Psychiatry 46, 482–483.CrossRefGoogle 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 ScholarPubMed
Wong, D. F., Wagner, H. N., Dannals, R. F., Links, J. M., Frost, J. J., Ravert, H. T., Wilson, A. A., Rosenbaum, A. E., Gjedde, A., Douglass, K. H., Petronis, J. D., Folstein, M. F., Touing, J. K., Burns, H. D. & Kuhar, M. J. (1984). Effects of age on dopamine and serotonin receptors measured by positron tomography in the living brain. Science 226, 1393–1396.CrossRefGoogle Scholar
Zemlan, F. P., Hirschowitz, J., Sautter, F. & Garver, G. L. (1986). Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine. Psychiatry Research 18, 239–255.CrossRefGoogle ScholarPubMed
Zubin, J., Steinhauer, S. R., Day, R. & van Kammen, D. P. (1985). Schizophrenia at the crossroads: a blueprint for the 80s. Comprehensive Psychiatry 26, 217–240.CrossRefGoogle ScholarPubMed