Hormonal Responses to D-Amphetamine in Schizophrenia

  • Daniel P. Van Kammen
  • S. Charles Schulz
  • Alan D. Rogol


The effects of D-amphetamine in man and particularly in schizophrenic patients have been studied because of the hypothesized disturbance in the dopamine (DA) and norepinephrine (NE) systems in the illness. In this chapter, we incorporated several of our studies of the effects of D-amphetamine on hormonal secretion. We studied PRL, which is under tonic inhibitory control of DA (MacLeod and Lamberts, 1979; Clemens and Shaar, 1980; Meites, 1973), growth hormone (GH), which can be released by both NE (Massara and Camanni, 1972) and DA (Malas et al., 1983; Meltzer et al., 1979), and Cortisol, which is under partial control of NE (Sachar et al., 1981). Furthermore, we examined immunoreactive (i.r.) β-endorphin levels assuming that the euphoria that is experienced may be mediated by endorphin release as well as the hypothesized β-endorphin disturbance in schizophrenia (Berger et al., 1980; Davis et al., 1980; Bloom et al., 1976).


Growth Hormone Schizophrenic Patient Normal Volunteer Growth Hormone Response Growth Hormone Release 
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. Aarskog, D., Ferang, F. Ø., Kløve, H., Støa, K. F., and Thorsen, T., 1977, The effect of stimulant drugs, dextroamphetamine and methylphenidate, on secretion of growth hormone in hyperactive children, J. Pediatr. 90:136.PubMedCrossRefGoogle Scholar
  2. Berger, P. A., Watson, S. J., Akil, H., Elliot, G. R., Rubin, R. T., Pfefferbaum, A., Davis, K. L., Barchas, J. D., and Li, C. H., 1980, Beta-endorphin and schizophrenia, Arch. Gen. Psychiatry 37:635.PubMedCrossRefGoogle Scholar
  3. Besser, G. M., Butler, P. W. P., Landon, J., and Rees, L., 1969, Influence of amphetamines on plasma corticosteroid and growth hormone levels in man, Br. Med. J. 4:528.PubMedCrossRefGoogle Scholar
  4. Bloom, F., Segal, D., Ling, N., and Guillemin, R., 1976, Endorphins: Profound behavioral effects in rats suggest new etiological factors in mental illness, Science 194:630.PubMedCrossRefGoogle Scholar
  5. Brown, W. A., 1977, Psychologic and neuroendocrine response to methylphenidate, Arch. Gen. Psychiatry 34:1103.PubMedCrossRefGoogle Scholar
  6. Brown, W. A., Corriveau, D. P., and Ebert, M. H., 1978, Acute psychologic and neuroendocrine effects of dextroamphetamine and methylphenidate, Psychopharmacology 58:189.PubMedCrossRefGoogle Scholar
  7. Butler, P. W. P., Besser, G. M., and Steinberg, H., 1968, Changes in plasma Cortisol induced by dexamphetamine and chlordiazepoxide given alone and in combination in man, J. Endocrinol. 40:391.PubMedCrossRefGoogle Scholar
  8. Camanni, F., Massara, F., and Molinatti, G. M., 1974, Propranolol enhancement of l-DOPA induced growth hormone stimulation, Biomedicine 21:241.PubMedGoogle Scholar
  9. Checkley, S. A., 1979, Corticosteroid and growth hormone responses to methylamphetamine in depressive illness, Psychol. Med. 9:107.PubMedCrossRefGoogle Scholar
  10. Checkley, S. A., and Crammer, J. L., 1977, Hormone responses to methylamphetamine in depression: A new approach to the noradrenaline depletion hypothesis, Br. J. Psychiatry 131:582.PubMedCrossRefGoogle Scholar
  11. Clemens, J. A., and Shaar, C. J., 1980, Control of prolactin secretion in mammals, Fed. Proc. 39:2588.PubMedGoogle Scholar
  12. Cohen, M. R., Nurnberger, J. I., Pickar, D., Gershon, E., and Bunney, W. E., Jr., 1981, Dextroamphetamine infusions in normals result in correlated increases of plasma β-endorphin and Cortisol immunoreactivity, Life Sci. 29:1243.PubMedCrossRefGoogle Scholar
  13. Davis, G. C., Buchsbaum, M. S., Naber, D., and van Kammen, D. P., 1980, Effects of opiates and opiate antagonists on somatosensory evoked potentials in patients with schizophrenia and normal adults, in: Recent Advances in Biological Psychiatry (C. Perris and L. von Knorring, eds.), pp. 73–80, Karger, Basel.Google Scholar
  14. Dommissee, P., Schulz, S. C., Narasimhachari, N., and Hamer, R., 1982, The neuroendocrine and behavioral response to dextro-amphetamine in normal individuals, Presented at the Society of Biological Psychiatry, Toronto.Google Scholar
  15. Dubois, M., Pickar, D., Cohen, M. R., Roth, Y. F., MacNamara, T., and Bunney, W. E., Jr., 1981, Surgical stress in humans is accompanied by an increase in plasma beta-endorphin immunoreactivity, Life Sci. 29:1249.PubMedCrossRefGoogle Scholar
  16. Ebert, M. H., van Kammen, D. P., and Murphy, D. L., 1976, Plasma levels of amphetamine and behavioral response, in: Pharmacokinetics of Psychoactive Drugs (L. A. Gottschalk and S. Merlis, eds.), pp. 157–169, Spectrum, New York.Google Scholar
  17. Greenhill, L. L., Puig-Antich, J., Chambers, W., Rubinstein, B., Halpern, F., and Schar, E. J., 1981, Growth hormone, prolactin, and growth responses in hyperkinetic males treated with d-amphetamine, J. Am. Acad. Child Psychiatry 20:84.PubMedCrossRefGoogle Scholar
  18. Groves, P. M., Staunton, D. A., Wilson, C. J., and Young, S. J., 1979, Sites of action of amphetamine intrinsic to catecholaminergic nuclei: Catecholaminergic presynaptic dendrites and axons, Prog. Neuro-Psychopharmacol. 3:315.CrossRefGoogle Scholar
  19. Halbreich, U., Asnis, G. M., Halpern, F., Tabrizi, M. A., and Sachar, E. J., 1980, Diurnal growth hormone responses to dextroamphetamine in normal young men and post-menopausal women, Psychoneuroendocrinology 5:339.PubMedCrossRefGoogle Scholar
  20. Halbreich, U., Sachar, E. J., Asnis, G. M., Nathan, R. S., and Halpern, F. S., 1981, The prolactin response to intravenous dextroamphetamine in normal young men and postmenopausal women, Life Sci. 28:2337.PubMedCrossRefGoogle Scholar
  21. Halbreich, U., Sachar, E. J., Asnis, G. M., Quitkin, F., Nathan, R. S., Halpern, F. S., and Klein, D. F., 1982, Growth hormone response to dextroamphetamine in depressed patients and normal subjects, Arch. Gen. Psychiatry 39:189.PubMedCrossRefGoogle Scholar
  22. Janowsky, D. S., Leichner, P., Parker, D., Judd, L. L., Huey, L., and Clopton, P., 1978, The effect of methylphenidate on serum growth hormone: Influence of antipsychotic drugs and diagnosis, Arch. Gen. Psychiatry 35:1384.PubMedCrossRefGoogle Scholar
  23. Kalin, N. H., Risch, S. C., Cohen, R. M., Insel, T., and Murphy, D. L., 1980, Dexamethasone fails to suppress β-endorphin plasma concentrations in humans and rhesus monkeys, Science 209:827.PubMedCrossRefGoogle Scholar
  24. Kuczenski, R., 1977, Biphasic effects of amphetamine on striatal dopamine dynamics, Eur. J. Pharmacol. 46:249.PubMedCrossRefGoogle Scholar
  25. Langer, G., and Matussek, N., 1977, Dextro- and L-amphetamine are equipotent in releasing human growth hormone, Psychoneuroendocrinology 2:379.PubMedCrossRefGoogle Scholar
  26. Langer, G., Heinze, G., Reim, B., and Matussek, N., 1976, Reduced growth hormone responses to amphetamine in “endogenous” depressive patients: Studies in normal, “reactive” and “endogenous” depressive, schizophrenic, and chronic alcoholic subjects, Arch. Gen. Psychiatry 33:1471.PubMedCrossRefGoogle Scholar
  27. Lu, K. H., and Meites, J., 1971, Inhibition by L-Dopa and monoamine oxidase inhibitors of pituitary prolactin release; stimulation by methyl-dopa and d-amphetamine, Proc. Soc. Exp. Biol. Med. 137:480.Google Scholar
  28. MacLeod, R. M., and Lamberts, S. W. J., 1979, Clinical and fundamental correlates in dopaminergic control of prolactin secretion, in: Neuroendocrine Correlates in Neurology and Psychiatry (E. E. Müller and A. Agnoli, eds.), Elsevier/North-Holland, Amsterdam.Google Scholar
  29. Malas, K. L., van Kammen, D. P., DeFraites, E. J., Brown, G., and Gold, P. W., 1983, Reduced growth hormone response to apomorphine in schizophrenic patients with poor premorbid functioning, Biol. Psychiatry 18:255.PubMedGoogle Scholar
  30. Marantz, R., Sachar, E. J., Weitzman, E., and Sassin, J., 1976, Cortisol and GH responses to d-and l-amphetamine in monkeys, Endocrinology 99:459.PubMedCrossRefGoogle Scholar
  31. Massara, F., and Camanni, F., 1972, Effects of various adrenergic receptor stimulating and blocking agents on human growth hormone secretion, J. Endocrinol. 54:195.PubMedCrossRefGoogle Scholar
  32. Meites, J., 1973, Human Prolactin, American Elsevier, New York.Google Scholar
  33. Meltzer, H. Y., Fessier, R. G., Simonovic, M., Docherty, J., and Fang, V. S., 1979, Effect of d-and l-amphetamine on rat plasma prolactin levels, Psychopharmacology 61:63.PubMedCrossRefGoogle Scholar
  34. Meltzer, H. Y., Bush, D., and Fang, V. S., 1981, Hormones, dopamine receptors, and schizophrenia, Psychoneuroendocrinology 6:17.PubMedCrossRefGoogle Scholar
  35. Naber, D., Pickar, D., Post, R. M., van Kammen, D. P., Waters, R. N., Ballenger, J. C., and Goodwin, F. K., 1981, Endogenous opioid activity and β-endorphin immunoreactivity in CSF of psychiatric patients and normal volunteers, Am. J. Psychiatry 138:1457.PubMedGoogle Scholar
  36. Nurnberger, J. I., Jr., Gershon, E. S., Simmons, S., Ebert, M., Kessler, L. R., Dibble, E. D, Jimerson, S. S., Brown, G. M., Gold, P. W., Jimerson, D. C., Guroff, J. J., and Storch, F. I., 1982, Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and “well state” bipolar patients Psychoneuroendocrinology, 7:163–176.PubMedCrossRefGoogle Scholar
  37. Nürnberger, J. I., Jr., Gershon, E. S., Jimerson, D. C., Buchsbaum, M. S., Gold, P. W., Brown, G., and Ebert, M., 1981, Pharmacogenetics of d-amphetamine response in man, in: Genetic Research Strategies for Psychobiology and Psychiatry (E. S. Gershon, S. Matthysse, X. O. Breakefield, and R. D. Ciaranello, eds.), pp. 257–268, Boxwood Press, New York.Google Scholar
  38. Parkes, J. D., Debono, A. G., Jenner, P., and Walters, J., 1977, Amphetamines, growth hormone and narcolepsy, Br. J. Clin. Pharmacol. 4:343.PubMedGoogle Scholar
  39. Ravitz, A. J., and Moore, K. E., 1977, Effects of amphetamine, methylphenidate and cocaine on serum prolactin concentrations in the male rat, Life Sci. 21:267.PubMedCrossRefGoogle Scholar
  40. Rees, L., Butler, P. W. P., Gosling, C., and Besser, G. M., 1970, Adrenergic blockade and the corticosteroid and growth hormone responses to methylamphetamine, Nature (London) 228:565.CrossRefGoogle Scholar
  41. Sachar, E. J., Asnis, G., Nathan, R. S., Halbreich, U., Tabrizi, M. A., and Halpern, F. S., 1980, Dextroamphetamine and Cortisol in depression: Morning plasma Cortisol levels suppressed, Arch. Gen. Psychiatry 37:755.PubMedCrossRefGoogle Scholar
  42. Sachar, E. J., Halbreich, U., Asnis, G. M., Nathan, R. S., Halpern, F. S., and Ostrow, L., 1981, Paradoxical Cortisol responses to dextroamphetamine in endogenous depression, Arch. Gen. Psychiatry 38:1113.PubMedCrossRefGoogle Scholar
  43. Schulz, S. C., Wagner, R., van Kammen, D. P., Rogol, A. D., Davis, G. C., Wyatt, R. J., Pickar, D., Bunney, W. E., Jr., and Li, C. H., 1980, Prolactin response to beta-endorphin in man, Life Sci. 27:1735.PubMedCrossRefGoogle Scholar
  44. Schulz, S. C., van Kammen, D. P., Pickar, D., Cohen, M., and Naber, D., 1982, Response of plasma beta-endorphin immunoreactivity: d-Amphetamine and placebo in schizophrenic patients, Psychiatry Res. 7:171.PubMedCrossRefGoogle Scholar
  45. Schulz, S. C., van Kammen, D. P., Rogol, A. D., Ebert, M., Pickar, D., Cohen, M. R., and Naber, D., 1981b, Amphetamine increases prolactin but not growth hormone or endorphins in schizophrenic patients, Psychopharmacol. Bull. 17:193.Google Scholar
  46. Slater, S., de la Vega, C. E., Skyler, J., and Murphy, D. L., 1976, Plasma prolactin stimulation by fenfluramine and amphetamine, Psychopharmacol. Bull. 12:26.PubMedGoogle Scholar
  47. Spitzer, R. L., Endicott, J. E., and Robbins, E., 1975, 1978, Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders, New York Psychiatric Institute, New York.Google Scholar
  48. van Kammen, D. P., 1979, The dopamine hypothesis of schizophrenia revisited, Psychoneuroen-docrinology 4:37.CrossRefGoogle Scholar
  49. van Kammen, D. P., Docherty, J. P., Marder, S. R., Siris, S. G., and Bunney, W. E., Jr., 1978, d-Amphetamine raises serum prolactin in man: Evaluations after chronic placebo, lithium and pimozide treatment, Life Sci. 23:1487.Google Scholar
  50. van Kammen, D. P., Docherty, J. P., Marder, S. R., Schulz, S. C., and Bunney, W. E., Jr., 1980, Lack of behavioral supersensitivity to d-amphetamine after pimozide withdrawal, Arch. Gen. Psychiatry 37:287.PubMedCrossRefGoogle Scholar
  51. van Kammen, D. P., Docherty, J. P., Marder, S. R., and Bunney, W. E., Jr., 1981, Acute amphetamine response predicts antidepressant and antipsychotic responses to lithium carbonate in schizophrenic patients, Psychiatry Res. 4:313.PubMedCrossRefGoogle Scholar
  52. van Kammen, D. P., Docherty, J. P., and Bunney, W. E., Jr., 1982a, Prediction of early relapse after pimozide discontinuation by response to d-amphetamine during pimozide treatment, Biol. Psychiatry 17:233.PubMedGoogle Scholar
  53. van Kammen, D. P., Docherty, J. P., Marder, S. R., Schulz, S. C., Dalton, L., and Bunney, W. E., Jr., 1982b, Antipsychotic effects of pimozide in schizophrenia: Treatment response prediction with acute dextroamphetamine administration, Arch. Gen. Psychiatry 39:261.PubMedCrossRefGoogle Scholar
  54. van Kammen, D. P., Bunney, W. E., Jr., Docherty, J. P., Marder, S. R., Ebert, M. H., Rosenblatt, J. E., and Rayner, J. N., 1982c, d-Amphetamine induced heterogeneous changes in psychotic behavior in schizophrenia, Am. J. Psychiatry 139:991.Google Scholar
  55. van Kammen, D. P., Schulz, S. C., and Davis, G. C., d-Amphetamine raises Cortisol in schizophrenic patients with and without naltrexone pre treatment, in preparation.Google Scholar
  56. Wells, B., Silverstone, T., and Rees, L., 1978, The effect of oral dextroamphetamine on prolactin secretion in man, Neuropharmacology 17:1060.PubMedCrossRefGoogle Scholar
  57. Zacur, H.A., Foster, G. V., and Tyson, J. E., 1976, Multifactorial regulation of prolactin secretion, Lancet I:410.CrossRefGoogle Scholar
  58. Zahn, T., 1980, Predicting outcome from measures of attention and autonomic functioning, in: Perspectives in Schizophrenia Research (C. Baxter and T. Melneche, eds.), pp. 81–106, Raven Press, New York.Google Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Daniel P. Van Kammen
    • 1
  • S. Charles Schulz
    • 1
  • Alan D. Rogol
    • 2
  1. 1.Western Psychiatric Institute and ClinicUniversity of PittsburghPittsburghUSA
  2. 2.University of Virginia Medical CenterCharlottesvilleUSA

Personalised recommendations