Tryptophan Pyrrolase—A Biochemical Factor in Depressive Illness? | The British Journal of Psychiatry | Cambridge Core (original) (raw)

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).

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., 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, . Edited by Cumings, J. N., and Kramer, M. Blackwell-Oxford. 257–70.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. (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., 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

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