Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-24T14:20:24.450Z Has data issue: false hasContentIssue false
  • English
  • Français

Tryptophan Pyrrolase—A Biochemical Factor in Depressive Illness?

Published online by Cambridge University Press:  29 January 2018

G. Curzon
G. Curzon*
Affiliation:
Reader in Biochemistry, Department of Chemical Pathology, Institute of Neurology, London
Get access Rights & Permissions [Opens in a new window]

Extract

Reserpine, which depletes brain amines, not infrequently causes depression (Bunney and Davis, 1965), whereas monoamine oxidase inhibitors (MAOI) which raise brain amine levels (Maclean et al., 1965) may alleviate depressive symptoms. The alleviation has been reported to be enhanced by tryptophan (Coppen et al., 1967), which is a precursor of the amines 5-hydroxytryptamine (5HT) and tryptamine. The apparent prophylaxis by tryptophan of an annual episode of depression has also been reported (Hertz and Sulman, 1968). These findings suggest that elevation of one or both of the above amines is responsible for the therapeutic effect of MAOI, and that their insufficiency may be responsible for symptoms of the disease. Defective 5HT synthesis in depressive illness is indicated by a number of findings. (1) Depressed patients responding to the MAOI drug iproniazid were found in two studies (Pare and Sandier, 1959; Praag and Leijnse, 1963), though not in a third (Burgermeister et al., 1963), to have a lower initial urinary excretion of the 5HT metabolite 5-hydroxyindole acetic acid (5HIAA) than those who did not respond. (2) Depressed patients have a low content of 5HIAA in the lumbar cerebrospinal fluid (Ashcroft et al., 1966), which rises on recovery. Although work using animals (Guldberg and Yates, 1968; Eccleston et al., 1968) shows that changes in brain 5HT are paralleled by changes of 5HIAA in the CSF, the significance of this result is not altogether clear, as lumbar 5HIAA depends not only on brain 5HT metabolism but also on 5HIAA transport within the CSF (Ashcroft et al., 1966). Furthermore, a small group of acute schizophrenics on phenothiazines also had low 5HIAA. (3) There is some direct evidence of low 5HT (Shaw et al., 1967) or 5HIAA (Bourne et al., 1968) in the hindbrains of depressive suicides. (4) While single doses of 5-hydroxytryptophan, the immediate precursor of 5HT, do not alleviate depression, the remission of a prolonged episode of severe depression by administration of 5-hydroxytryptophan for five days has been reported (Persson and Roos, 1967).

Type
Research Article
Information
The British Journal of Psychiatry , Volume 115 , Issue 529 , December 1969 , pp. 1367 - 1374
Copyright
Copyright © Royal College of Psychiatrists, 1969 

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

Altman, K., and Greengard, O. (1966). ‘Correlation of kynurenine excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction.’ J. clin. Invest., 45, 1527–34.CrossRefGoogle ScholarPubMed
Ashcroft, G. W., Crawford, T. B. B., Eccleston, D., Sharman, D. F., Macdougall, E. J., Stanton, J. B., and Binar, J. K. (1966). ‘5-Hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological disease.’ Lancet, ii, 1049–52.CrossRefGoogle Scholar
Becking, G. C., and Johnson, W. J. (1967). ‘The inhibition of tryptophan pyrrolase by allopurinol, an inhibitor of xanthine oxidase.’ Canad. J. Biochem., 45, 1667–72.Google ScholarPubMed
Benassi, C. A., Benassi, P., Allegri, G., and Ballarin, P. (1961). ‘Tryptophan metabolism in schizophrenic patients.’ J. Neurochem., 7, 264–70.CrossRefGoogle Scholar
Bliss, E. L. (1967). ‘Sleep in schizophrenia and depression—studies of sleep loss in man and animals.’ Res. Publ. Ass. new. ment. Dis., 45, 195–210.Google Scholar
Bliss, E. L., Migeon, C. J., Branch, C. H. H., and Samuels, L. T. (1956). ‘Reaction of adrenal cortex to emotional stress.’ Psychosom. Med., 18, 56–76.CrossRefGoogle ScholarPubMed
Bourne, H. R., Bunney, W. E., Colburn, R. W., Davis, J. M., Davis, J. N., Shaw, D. M., and Coppen, A. (1968). ‘Noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the hindbrains of suicidal patients.’ Lancet, ii, 805–8.CrossRefGoogle Scholar
Bridges, P. K., and Jones, M. T. (1966). ‘The diurnal rhythm of plasma cortisol concentration in depression.’ Brit. J. Psychiat., 112, 1257–61.CrossRefGoogle ScholarPubMed
Brooksbank, B. W. L., and Coppen, A. (1967). ‘Plasma 11-hydroxycorticoids in affective disorders.’ Brit, J. Psychiat., 113, 395–404.CrossRefGoogle Scholar
Bunney, W. E., and Davis, J. M., (1965). ‘Norepinephrine in depressive reactions. A review.’ Arch. gen. Psychiat., 13, 483–94CrossRefGoogle ScholarPubMed
Burgermeister, J. J., Dick, P., Garrone, G., Guggisberg, M., and Tissot, R. (1963). ‘Urinary excretion of 5-hydroxyindoleacetic acid (5HIAA) in 150 patients with depressive syndrome and maniacal agitation. (Its modifications by 5-hydroxytryptophan loading and therapy in the depressive states.)’ Pr. méd., 71, 1116–8.Google Scholar
Bush, I. E. (1962). ‘Chemical and biological factors in the activity of adrenocortical steroids.’ Pharmacol. Rev. 14, 317–445.Google ScholarPubMed
Butler, P. W. P., and Besser, G. M. (1968). ‘Pituitary-adrenal function in severe depressive disease.’ Lancet, i, 1234–6.CrossRefGoogle Scholar
Cass, R., and Marshall, P. B. (1962). ‘Effect of adrenocortical hormones on tissue histamine and 5-hydroxytryptamine in the rat.’ Arch. int. Pharmacodyn., 136, 311–32.Google ScholarPubMed
Cazzullo, C. L., Mangoni, H., and Mascherpa, A. (1966). ‘Tryptophan metabolism in affective psychoses.’ Brit.J. Psychiat., 112, 157–62.CrossRefGoogle ScholarPubMed
Chytil, F. (1968). ‘Activation of liver tryptophan oxygenase by adenosine 3′, 5′-phosphate and by other purine derivatives.’ J. biol. Chem., 243, 893–9.CrossRefGoogle Scholar
Given, M., and Knox, W. E. (1960). ‘The specificity of tryptophan analogues as inducers, substrates, inhibitors and stabilizers of liver tryptophan pyrrolase.’ J. biol. Chem., 235, 1716–8.Google Scholar
Clark, L. D., Bauer, W., and Cobb, S. (1952). ‘Preliminary observations on mental disturbances occurring in patients under therapy with cortisone and ACTH.’ New Engl. J. Med., 246, 205–216.CrossRefGoogle Scholar
Cleghorn, R. A. (1951). ‘Adrenal cortical insufficiency: psychological and neurological observations.’ Canad. med. Ass. J., 65, 449–54.Google ScholarPubMed
Coppen, A. (1968). ‘Depressed states and indolealkylamines.’ Adv. Pharmacol., 6B, 283–91.CrossRefGoogle Scholar
Coppen, A. (1967). ‘The biochemistry of affective disorders.’ Brit. J. Psychiat., 113, 1237–64.CrossRefGoogle ScholarPubMed
Coppen, A., Shaw, D. M., Herzberg, B., and Maggs, R. (1967) ‘Tryptophan in the treatment of depression.’ Lancet, ii, 1178–80.Google Scholar
Corrodi, H., Fuxe, K., and Hökfelt, T. (1968). ‘The effect of immobilisation stress on the activity of central monoamine neurons.’ Life Sci., 7, 107–12.CrossRefGoogle ScholarPubMed
Cremata, V. Y., and Koe, B. K. (1966). ‘Clinical pharmacological evaluation of p-chlorophenylalanine; a new serotonin-depleting agent.’ Clin. Pharmac. Therap., 7, 768–76.Google ScholarPubMed
Csaba, B., Kassay, L., and Muszbek, L. (1967). ‘Role of adrenal cortical hormone in controlling the level of histamine and 5HT of rat tissue.’ Acta biochem. biophys. Acad. Sci. (Hung.), 2 (suppl.), 73.Google Scholar
Curzon, G. (1965). ‘The biochemistry of depression.’ In Biochemical Aspects of Neurological Disorders, 2nd series. Edited by Cumings, J. N., and Kramer, M. Blackwell-Oxford. 257–70.Google Scholar
Curzon, G. and Bridges, P. K. (1969). (Unpublished work.) Google Scholar
Curzon, G. and Green, A. R. (1968). ‘Effect of hydrocortisone on rat brain 5-hydroxytryptamine.’ Life Sci., 7, 657–63.CrossRefGoogle Scholar
Curzon, G. and Green, A. R. (1969). ‘Liver tryptophan pyrrolase activity and brain 5-hydroxytryptamine.’ Biochem. J., 111, 15.CrossRefGoogle ScholarPubMed
Dewhurst, W. G. (1965). ‘On chemical basis of mood.’ J. psychosom. Res., 9, 115–27.CrossRefGoogle ScholarPubMed
Dewhurst, W. G. (1968). ‘New theory of cerebral amine function and its clinical application.’ Nature, 218, 1130–3.CrossRefGoogle ScholarPubMed
De Maio, D. (1959). ‘Influence of adrenalectomy and hypophysectomy on cerebral serotonin.’ Science, 129, 1678–9.CrossRefGoogle ScholarPubMed
Doig, R. J., Mummery, R. V., Willis, M. R., and Elkes, A. (1966). ‘Plasma cortisol levels in depression.’ Brit. J. Psychiat., 112, 1263–7.CrossRefGoogle ScholarPubMed
Ebadi, M. S., Russell, R. L., and McCoy, E. E. (1968). ‘The inverse relationship between the activity of pyridoxal kinase and the level of biogenic amines in rabbit brain.’ J. Neurochem., 15, 659–65.CrossRefGoogle ScholarPubMed
Eccleston, D., Ashcroft, G. W., Crawford, T. B. B., and Loose, R. J. (1966). ‘Some observations on the estimation of tryptamine in tissues.’ J. Neurochem., 13, 93–101.CrossRefGoogle ScholarPubMed
Eccleston, D., Ashcroft, G. W., Moir, A. T. B., Parker-Rhodes, A., Lutz, W., and O'Mahoney, D. P. (1968). ‘A comparison of 5-hydroxyindoles in various regions of dog brain and cerebrospinal fluid.’ J. Neurochem., 15, 947–57.CrossRefGoogle ScholarPubMed
Efron, G. H., and Gessa, G. L. (1963). ‘Failure of ethanol and barbiturates to alter brain monoamine content.’ Arch. int. Pharmacodyn., 142, 111–6.Google Scholar
Faurbye, A., and Pind, K. (1964). ‘Investigations on the tryptophane metabolism (via kynurenine) in schizophrenic patients.’ Acta psychiat. Scand., 40, 244–8.CrossRefGoogle ScholarPubMed
Fawcett, J. A., and Bunney, W. E. (1967). ‘Pituitary adrenal function and depression. An outline for research.’ Arch. gen. Psychiat., 16, 517–35.CrossRefGoogle ScholarPubMed
Gal, E. M., Drewes, P. A., and Barraclough, C. A. (1962). ‘Effect of reserpine on the metabolism of serotonin in tryptophan deficient rats.’ Proc. 1st Int. Pharmacol. Meeting, 8, 107–18.Google Scholar
Gal, E. M., Heater, R. D., and Millard, S. A. (1968). ‘Studies on the metabolism of 5-hydroxytryptamine. VI. Hydroxylation and amines in cold stressed reserpinized rats.’ Proc. Soc. exp. Biol. Med., 128, 412–5.CrossRefGoogle Scholar
Garattini, S., Lamesta, L., Mortari, A., Palma, V., and Valzelli, L. (1961). ‘Pharmacological and biochemical effects of 5-hydroxytryptamine in adrenalectomised rats.’ J. Pharm. Pharmacol., 13, 385–8.Google ScholarPubMed
Giarman, N. J., and Pepeu, G. (1962). ‘Drug induced changes in brain acetylcholine.’ Brit. J. Pharmacol., 19, 226–34.Google ScholarPubMed
Gibbons, J. L. (1964). ‘Cortisol secretion rate in depressive illness.’ Arch. gen. Psychiat., 10, 572–5CrossRefGoogle ScholarPubMed
Gibbons, J. L., and McHugh, P. R. (1962). ‘Plasma cortisol in depressive illness.’ J. psychiat. Res., 1, 162–71.CrossRefGoogle ScholarPubMed
Green, A. R., and Curzon, G. (1968). ‘Decrease of 5-hydroxytryptamine in the brain provoked by hydrocortisone and its prevention by Allopurinol.’ Nature, 220, 1095–7.CrossRefGoogle ScholarPubMed
Guldber, H. C., and Yates, C. M. (1968). ‘Some studies of the effects of chlorpromazine, reserpine and dihydroxyphenylalanine on the concentrations of homovanillic acid, 3, 4-dihydroxyphenylacetic acid and 5-hydroxyindol-3-ylacetic acid in ventricular cerebrospinal fluid of the dog using the technique of serial sampling of the cerebrospinal fluid.’ Brit. J. Pharmacol., 33, 457–71.Google Scholar
Hardeland, R., and Rensing, L. (1968). ‘Circadian oscillation in rat liver tryptophan pyrrolase and its analysis by substrate and hormone induction.’ Nature, 219, 619–21.CrossRefGoogle ScholarPubMed
Hertz, T., and Sulman, F. G. (1968). ‘Preventing depression with tryptophan.’ Lancet, i, 531–2.CrossRefGoogle Scholar
Hullin, R. P., Bailey, A. D., McDonald, R., Dransfield, G. A., and Milne, H. B. (1967). ‘Variations in 11-hydroxycorticosteroids in depression and manic-depressive psychosis.’ Brit. J. Psychiat., 113, 593–600.CrossRefGoogle Scholar
Jouvet, M. (1968). ‘Insomnia and decrease of cerebral 5-hydroxytryptamine after destruction of the raphé system in the cat.’ Adv. in Pharmacol., 6B, 265–82.CrossRefGoogle Scholar
Kato, R., and Valzelli, L. (1958). ‘Cortisone e 5-idrossitriptamina cerebrale.’ Boll. Soc. Ital. Biol. sper., 34, 1402–4.Google Scholar
Knapp, M. S., Keane, P. M., and Wright, J. G. (1967). ‘Circadian rhythm of plasma 11-hydroxycorticoids in depressive illness, congestive heart failure, and Cushing's syndrome.’ Brit. med. J., ii, 27–30.CrossRefGoogle Scholar
Knox, W. E. (1951). ‘Two mechanisms which increase in vivo liver tryptophan peroxidase activity: specific enzyme adaptation and stimulation of pituitary-adrenal system.’ Brit. J. exp. Path., 32, 462–9.Google ScholarPubMed
Knox, W. E. and Auerbach, V. H. (1955). ‘Hormonal control of tryptophan peroxidase in rat.’ J. biol. Chem., 214, 307–13.CrossRefGoogle Scholar
Knox, W. E. Piras, M. M., and Tokuyama, K. (1966). ‘Induction of tryptophan pyrrolase in rat liver by physiological amounts of hydrocortisone and secreted glucocorticoids.’ Enzym. biol. clin., 7, 1–10.CrossRefGoogle ScholarPubMed
Krieger, D., and Krieger, T. (1967). ‘Circadian pattern of plasma 17-hydroxycorticosteroid: alteration by anticholinergic agents.’ Science, 155, 1421–2.CrossRefGoogle ScholarPubMed
Lapin, I. P., and Oxenkrug, G. F. (1969). ‘Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect.’ Lancet, i, 132–6.CrossRefGoogle Scholar
Maclean, R., Nicholson, W. J., Pare, C. M. B., and Stacey, R. S. (1965). ‘Effect of monoamineoxidase inhibitors on the concentrations of 5-hydroxytryptamine in the human brain.’ Lancet, ii, 205–8.CrossRefGoogle Scholar
Mandell, A. J. (1963). ‘Some determinants of indole excretion in man.’ Recent Adv. in biol. Psychiat., 5, 237–256.Google Scholar
Mandell, A. J. and Rubin, R. T. (1966). ‘ACTH induced changes in tryptophan turnover along induceable pathways in man.’ Life Sci., 5, 1153–67.CrossRefGoogle ScholarPubMed
Mayer-Gross, W., Slater, E., and Roth, M. (1960). Clinical Psychiatry, 2nd edition. Cassell, London.Google Scholar
McClure, D. J. (1966). ‘The diurnal variation of plasma cortisol levels in depression.’ J. psychosom. Res., 10, 189–95.Google ScholarPubMed
McKennee, C. T., Timiras, P. S., and Quay, W. B. (1966). ‘Concentrations of 5-hydroxytryptamine in rat brain and pineal adrenalectomy and cortisol administration.’ Neuroendocrinol., 1, 251–6.Google Scholar
Moir, A. T. B., and Eccleston, D. (1968). ‘The effects of precursor loading in the cerebral metabolism in 5-hydroxyindoles.’ J. Neurochem., 15, 1093–108.CrossRefGoogle ScholarPubMed
Orth, D. N., Island, D. P., and Liddle, G. W. (1967). ‘Experimental alteration of the circadian rhythm in plasma cortisol (17-OHCS) concentration in man.’ J. clin. Endocrin., 7, 549–55.Google Scholar
Pare, C. M. B., and Sandler, M. (1959). ‘A clinical and biochemical study of a trial of iproniazid in the treatment of depression.’ J. Neurol. Neurosurg. Psychiat., 22, 247–51.CrossRefGoogle ScholarPubMed
Persson, T., and Roos, B. E. (1967). ‘5-Hydroxytryptophan for depression.’ Lancet, ii, 987.CrossRefGoogle Scholar
Pfeifer, A. K., Vizi, E. S., Satory, E., and Galambos, E. (1963). ‘The effect of adrenalectomy on the norepinephrine and serotonin content of the brain and on reserpine action in rats.’ Experientia, 19, 482–3.CrossRefGoogle ScholarPubMed
Praag, H. M. van, and Leijnse, B. (1963). ‘Die Bedeutung der Monoaminoxydasehemmung als antidepressives Prinzip, I.’ Psychopharmacologia, 4, 1–14.CrossRefGoogle Scholar
Price, J. M., Brown, R. R., and Peters, H. A. (1959). ‘Tryptophan metabolism in porphyria, schizophrenia and a variety of neurologic and psychiatric diseases.’ Neurology, 9, 456–68.CrossRefGoogle Scholar
Put, T. R., and Meduski, J. W. (1962). ‘The effect of adrenalectomy on the 5-hydroxytryptamine metabolism in the rat.’ Acta physiol. pharmacol. (Neerl.), 11, 240–56.Google ScholarPubMed
Radzialowski, F. M., and Bousquet, W. G. (1968). ‘Daily rhythmic variation in hepatic drug metabolism in the rat and mouse.’ J. Pharmacol., 163, 229–38.Google ScholarPubMed
Rapoport, M. I., Beisel, W. R., and Dinterman, R. E. (1968). ‘Circadian periodicity of tryptophan metabolism.’ J. clin. Invest., 47, 934–9.CrossRefGoogle ScholarPubMed
Resnick, R. H., Smith, G. T., and Gray, S. J. (1961). ‘Endocrine influences on tissue serotonin content of the rat.’ Amer. J. Physiol., 201, 571–3.CrossRefGoogle ScholarPubMed
Richter, D. (1967). ‘Tryptophan in metabolism in mental illness.’ In Amines and Schizophrenia. Edited by Himwich, H. E., Kety, S. S., and Smythies, J. R. Pergamon-Oxford.Google Scholar
Rivlin, R. S., and Knox, W. E. (1959). ‘Effects of age, body size and growth hormone on level of tryptophan peroxidase-oxidase in rat liver.’ Amer. J. Physiol., 197, 65–7.CrossRefGoogle ScholarPubMed
Roos, B. E., and Werdinius, B. (1962). ‘Effect of reserpine on the level of 5-hydroxyindoleacetic acid in brain.’ Life Sci., 3, 105–7.Google Scholar
Rosecrans, J. A. (1968). ‘Effects of an acute stressor on rat brain serotonin metabolism.’ Fed. Proc., 27, 540.Google Scholar
Rubin, R. T. (1967). ‘Adrenal cortical activity changes in manic-depressive illness.’ Arch. gen. Psychiat., 17, 671–9.CrossRefGoogle ScholarPubMed
Rubin, R. T., Young, W. M., and Clark, B. R. (1968). ‘17-Hydroxycorticosteroid and vanillylmandelic acid excretion in a rapidly cycling manic-depressive.’ Psychosom. Med., 30, 162–171.CrossRefGoogle Scholar
Sachar, E. J. (1967). ‘Corticosteroids in depressive illness. I A re-evaluation of control issues and the literature.’ Arch. gen. Psychiat., 17, 544–53.CrossRefGoogle Scholar
Scheving, L. E., Harrison, W. H., Gordon, P., and Pauly, J. E. (1968). ‘Daily fluctuation (circadian and ultradian) in biogenic amines of the rat brain.’ Amer. J. Physiol., 214, 166–73.CrossRefGoogle ScholarPubMed
Scheving, L. E., Harrison, W. H., Gordon, P., and Pauly, J. E. (1966). ‘Effect of light on corticosterone levels in plasma of rats.’ Amer. J. Physiol., 210, 1112–7.CrossRefGoogle ScholarPubMed
Shah, N. S., Stevens, S., and Himwich, H. E. (1968). ‘Effect of chronic administration of cortisone on the tryptophan induced changes in amine levels in the rat brain.’ Arch. int. Pharmacodyn., 171, 285–95.Google ScholarPubMed
Shaw, D. M., Camps, F. E., and Eccleston, E. G. (1967). ‘5-Hydroxytryptamine in the hind-brain of depressive suicides.’ Brit.J. Psychiat., 113, 1407–11.CrossRefGoogle ScholarPubMed
Sofer, S., and Gubler, C. J. (1962). ‘Studies on the effect of various procedures on the 5HT levels in the brain of rats.’ Fed. Proc., 21, 340 Google Scholar
Sourkes, T. L., Missala, K., and Madras, B. K. (1969). ‘Effect of yohimbine on tryptophan metabolism.’ J. Pharmacol., 165, 289–93.Google ScholarPubMed
Telford, J. M., and West, G. B. (1960). ‘The effects of corticosteroids and related compounds on the histamine and 5-hydroxytryptamine content of rat tissues.’ Brit. J. Pharmacol., 15, 532–9.Google ScholarPubMed
The Lancet (1967). ‘Editorial.’ Lancet, i, 317–8.Google Scholar
Towne, J. C, and Sherman, J. O. (1957). ‘Failure of acute bilateral adrenalectomy to influence brain serotonin levels in the rat.’ Proc. Soc. exp. Biol. Med., 103, 721–2.Google Scholar
Trethowan, W. H., and Cobb, S. (1952). ‘Neuropsychiatric aspects of Cushing's syndrome.’ Arch. Neurol. Psychiat., 67, 283–309.CrossRefGoogle ScholarPubMed
Weitzman, E. D., Rapport, M. M., McGregor, P., and Jacoby, J. (1968). ‘Sleep patterns of the monkey and brain serotonin concentration: effect of p-chlorophenylalanine.’ Science, 160, 1361–3.CrossRefGoogle ScholarPubMed
Westermann, E. O., Maickel, R. P., and Brodie, B. B. (1962). ‘On the mechanism of pituitary-adrenal stimulation by reserpine.’ J. Pharmacol., 138, 208–17.Google ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.