Neurotoxicity Research

, 4:147 | Cite as

The adrenochrome hypothesis of schizophrenia revisited

Article

Abstract

This paper reviews the current status of the adrenochrome theory of schizophrenia. An account is first given of all the experiments in which adrenochrome was reported to induce psychotomimetic effects in normal volunteers. Then the evidence is presented that adrenochrome may actually occur in the brain as a metabolite of adrenaline in the C2 group of adrenergic neurons in the medulla, together with an account of current ideas of the function of these neurons in higher limbic functions. Lastly the recent evidence is reviewed that the gene for the enzyme glutathione S-transferase is defective in schizophrenia. This enzyme detoxifies adrenochrome.

Keywords

Schizophrenia adrenochrome adrenaline C1-C3 adrenergic nuclei neuromelanin 

References

  1. Carlsson, A., Waters, A. and Hansson, L.O. (1994) “Neurotransmitter aberrations in schizophrenia: new findings”, In: Fog, R., Gerlach, J. and Hemmingston, R., eds, Schizophrenia. An Integrated View (Munksgard, Copenhagen), pp 332–343.Google Scholar
  2. Fornstedt, B., Brun, A., Rosengren, E. and Carlsson, A. (1989) “The apparent autoxidation rate of catechols in dopamine-rich areas of the brain increases with the degree of depigmentation of substantia nigra”, J. Neural. Trans. Park. Dis. Den. Sect. 1, 279–295.CrossRefGoogle Scholar
  3. Gai, W.P., Geffen, L.B., Denoroy, L. and Blessing, W.W. (1993) “Loss of C1 and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson’s disease”, Ann. Neurol. 33, 357–367.PubMedCrossRefGoogle Scholar
  4. Gertz, H-J. and Schmidt, L.G. (1991) “Low melanin content of substantia nigra in a case of neuroleptic malignant syndrome”, Pharmacopsychiatry 24, 93–95.PubMedCrossRefGoogle Scholar
  5. Greiner, A.C. and Nicholson, G.A. (1965) “Schizophrenia-melanism”, Lancet ii, 1165.CrossRefGoogle Scholar
  6. Grof, S., Vojtechovsky, M., Vitek, V. and Prankova, S. (1963) “Clinical and experimental study of central effects of adrenochrome”, J. Neuropsychiatr. 5, 33–50.Google Scholar
  7. Harada, S., Tachikawa, H. and Kawanishi, Y. (2001) “Glutathione S-transferase M1 gene deletion may be associated with susceptibility to certain forms of schizophrenia”, Biochem. Biophys Res. Comm. 281, 267–271.PubMedCrossRefGoogle Scholar
  8. Herbert, H. and Saper, C.B. (1992) “Organization of medullary adrenergic and noradrenergic projections to medullary periacqueductal gray matter in the rat”, J. Comp. Neurol. 315, 34–52.PubMedCrossRefGoogle Scholar
  9. Hoffer, A. (1957) “Adrenochrome in blood plasma”, Am. J. Psychiat. 114, 0.Google Scholar
  10. Hoffer, A., Osmond, H. and Smythies, J. (1954) “Schizophrenia: a new approach part 2”, J. Ment. Sci. 100, 29–45.PubMedGoogle Scholar
  11. Kaiya, H. (1980) “Neuromelanin, neuroleptics and schizophrenia”, Neuropsychobiology 6, 241–248.PubMedCrossRefGoogle Scholar
  12. Lew, J.Y., Matsumoto, Y., Pearson, J., Goldstein, M., Hokfelt, T. and Fuxe, K. (1977) “Localization and characterization of phenylethanolamine-N-methyltransferase in the brain of various mammalian species”, Brain Res. 119, 199–210.PubMedCrossRefGoogle Scholar
  13. Lindemann, E. (1935) “The psychopathological effects of drugs affecting the vegetative system”, Am. J. Psychiat. 91, 983–1008.Google Scholar
  14. Macarthur, H., Westfall, T.C., Riley, D.P., Misko, T.P. and Salvemini, D. (2000) “Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock”, Proc. Natl Acad. Sci. USA 97, 9753–9758.PubMedCrossRefGoogle Scholar
  15. Nagutsu, I., Ikemoto, K., Takeuchi, T., Arai, T., Karasawa, N., Fujii, T. and Nagatsu, T. (1996) “Phenylethanolamine-N-methyltransferase-immunoreactive nerve terminals afferent to the mouse substantia nigra”, Neurosci. Lett. 245, 41–44.CrossRefGoogle Scholar
  16. Osmond, H. and Smythies, J. (1952) “Schizophrenia: a new approach”, J. Ment. Sci. 98, 309–320.PubMedGoogle Scholar
  17. Otake, K., Ruggiero, D.A. and Nakamura, Y. (1995) “Adrenergic innervation of forebrain neurons that project to the paraventricular thalamic nucleus in the rat”, Brain Res. 697, 17–26.PubMedCrossRefGoogle Scholar
  18. Rico, B. and Cavada, C. (1998) “Adrenergic innervation of the monkey thalamus; an immunohistochemical study”, Neuroscience 84, 839–847.PubMedCrossRefGoogle Scholar
  19. Rinkel, M. and Solomon, A.C. (1957) “Chemical theories of psychosis”, J. Clin. Exp. Psychopath. 18, 323–334.PubMedGoogle Scholar
  20. Schwartz, B.E., Sem-Jacobsen, C. and Petersen, M.C. (1956) “Effects of mescaline, LSD-25 and adrenochrome on depths electrograms in man”, Arch. Neurol. Psychiat. 75, 579–587.Google Scholar
  21. Smythies, J. (1996) “On the function of neuromelanin” Proc. R Soc. London B 263, 487–489.CrossRefGoogle Scholar
  22. Smythies, J. (1999) “The neurotoxicity of glutamate, dopamine, iron and reactive oxygen species: functional interrelationships in health and disease: a review” Neurotox. Res. 1, 27–39.PubMedCrossRefGoogle Scholar
  23. Smythies, J. and Galzigna, L. (1998) “The oxidative metabolism of catecholamines in the brain: a review”, Biochim. Biophys Acta 1380, 19–162.Google Scholar
  24. Smythies, J.R., Morin, R.D. and Brown, G.B. (1979) “Identification of dimethyltryptamine and o-methylbufotenin in human cerebrospinal fluid by combined gas chromatography/mass spectrometry”, Biol. Psychiatr. 14, 549.Google Scholar
  25. Szara, S., Axelrod, J. and Perlin, S. (1958) “Is adrenochrome present in the blood?”, Am. J. Psychiatr. 115, 162–163.PubMedGoogle Scholar
  26. Szatmari, A., Hoffer, A. and Schneider, R. (1955) “The effect of adrenochrome and niacin on the electroencephalogram in epilepsy”, Am. J. Psychiat. 111, 603–616.PubMedGoogle Scholar
  27. Taubman, G. and Jantz, H. (1957) “Untersuchung über die dem adrenochrom zugeschrieben psychotoxischen wirkungen”, Nervenartz 28, 485–488.Google Scholar

Copyright information

© Springer 2002

Authors and Affiliations

  1. 1.Department of Psychology, Center for Brain and CognitionUniversity of California at San DiegoLa JollaUSA
  2. 2.Department of NeuropsychiatryInstitute of NeurologyLondonUK

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