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.
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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.
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.
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.
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.
Greiner, A.C. and Nicholson, G.A. (1965) “Schizophrenia-melanism”, Lancet ii, 1165.
Grof, S., Vojtechovsky, M., Vitek, V. and Prankova, S. (1963) “Clinical and experimental study of central effects of adrenochrome”, J. Neuropsychiatr. 5, 33–50.
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.
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.
Hoffer, A. (1957) “Adrenochrome in blood plasma”, Am. J. Psychiat. 114, 0.
Hoffer, A., Osmond, H. and Smythies, J. (1954) “Schizophrenia: a new approach part 2”, J. Ment. Sci. 100, 29–45.
Kaiya, H. (1980) “Neuromelanin, neuroleptics and schizophrenia”, Neuropsychobiology 6, 241–248.
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.
Lindemann, E. (1935) “The psychopathological effects of drugs affecting the vegetative system”, Am. J. Psychiat. 91, 983–1008.
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.
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.
Osmond, H. and Smythies, J. (1952) “Schizophrenia: a new approach”, J. Ment. Sci. 98, 309–320.
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.
Rico, B. and Cavada, C. (1998) “Adrenergic innervation of the monkey thalamus; an immunohistochemical study”, Neuroscience 84, 839–847.
Rinkel, M. and Solomon, A.C. (1957) “Chemical theories of psychosis”, J. Clin. Exp. Psychopath. 18, 323–334.
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.
Smythies, J. (1996) “On the function of neuromelanin” Proc. R Soc. London B 263, 487–489.
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.
Smythies, J. and Galzigna, L. (1998) “The oxidative metabolism of catecholamines in the brain: a review”, Biochim. Biophys Acta 1380, 19–162.
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.
Szara, S., Axelrod, J. and Perlin, S. (1958) “Is adrenochrome present in the blood?”, Am. J. Psychiatr. 115, 162–163.
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.
Taubman, G. and Jantz, H. (1957) “Untersuchung über die dem adrenochrom zugeschrieben psychotoxischen wirkungen”, Nervenartz 28, 485–488.
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Smythies, J. The adrenochrome hypothesis of schizophrenia revisited. neurotox res 4, 147–150 (2002). https://doi.org/10.1080/10298420290015827
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DOI: https://doi.org/10.1080/10298420290015827