Psychopharmacology

, Volume 87, Issue 2, pp 173–177 | Cite as

Tryptophan depletion causes a rapid lowering of mood in normal males

  • Simon N. Young
  • Scott E. Smith
  • Robert O. Pihl
  • Frank R. Ervin
Original Investigations

Abstract

Normal male human subjects ingested amino acid mixtures which were tryptophan-free, balanced or contained excess tryptophan. The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist. The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness (dysphoric distractor). Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes. Thus, both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males. This effect is probably mediated by a lowering of brain 5-hydroxytryptamine. Although the mood-lowering effect was not as great as that seen in depressed patients, our results suggest that low brain 5HT might be one factor precipitating depression in some patients.

Key words

Tryptophan 5-Hydroxytryptamine Depression 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beck AT (1976) Cognitive therapy and the emotional disorders. International Universities Press, New YorkGoogle Scholar
  2. Biggio G, Fadda D, Fanni P, Tagliamonte A, Gessa GL (1974) Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. Life Sci 14:1321–1329Google Scholar
  3. Chouinard G, Young SN, Bradwejn J, Annable L (1983) Tryptophan in the treatment of depression and mania. In: van Praag HM, Mendlewicz J (eds) Management of depressions with monoamine precursors, Advances in Biological Psychiatry, vol 10. S Karger, Basel, pp 47–66Google Scholar
  4. Coppen AJ (1967) The biochemistry of affective disorders. Br J Psychiatry 113:1237–1264Google Scholar
  5. Coppen A, Prange AJ, Whybrow PC, Noguera R (1972) Abnormalities of indoleamines in affective disorders. Arch Gen Psychiatry 26:474–478Google Scholar
  6. Cremata VY, Koe BK (1966) Clinical-pharmacological evaluation of p-chlorophenylalanine: a new serotonin-depleting agent. Clin Pharmacol Ther 7:768–776Google Scholar
  7. Denckla WD, Dewey HK (1967) The determination of tryptophan in plasma, liver and urine. J Lab Clin Med 69:160–169Google Scholar
  8. Engelman K, Lovenberg W, Sjoerdsma A (1967) Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome. New Engl J Med 227:1103–1108Google Scholar
  9. Gessa GL, Biggio G, Fadda F, Corsini GV, Tagliamonte A (1974) Effect of the oral administration of tryptophan-free amino acid mixtures on serum tryptophan, brain tryptophan and serotonin metabolism. J Neurochem 22:869–870Google Scholar
  10. Goodwin FK, Post RM (1983) 5-Hydroxytryptamine and depression: a model for the interaction of normal variance with pathology. Br J Clin Pharmacol 15:393S-405SGoogle Scholar
  11. Greenwood MH, Lader MH, Kantameneni BD, Curzon G (1975) The acute effects of oral (-)-tryptophan in human subjects. Br J Clin Pharmacol 2:165–172Google Scholar
  12. Lapin IP, Oxenkrug GF (1969) Intensification of the central serotonergic process as a possible determinant of the thymoleptic effect. Lancet i:132–136Google Scholar
  13. Lehmann J (1982) Tryptophan deficiency stupor — a new psychiatric syndrome. Acta Psychiatr Scand Suppl 300:1–57Google Scholar
  14. Lieberman HR, Corkin S, Spring BJ, Growdon JH, Wurtman RJ (1983) Mood, performance, and pain sensitivity: changes induced by food constituents. J Psychiatr Res 17:135–145Google Scholar
  15. Munro HN (1968) Role of amino acid supply in regulating ribosome function. Fed Proc 27:1231–1237Google Scholar
  16. Murphy DL, Campbell IC, Costa JL (1978) The brain serotonergic system in the affective disorders. Prog Neuro-Psychopharmacol 2:1–31Google Scholar
  17. Oldendorf WH, Szabo J (1976) Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am J Physiol 230:94–98Google Scholar
  18. Perez-Cruet J, Chase TN, Murphy DL (1974) Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan and neutral amino acids in humans. Nature 248:693–695Google Scholar
  19. Pihl RO, Yankofsky L (1979) Alcohol consumption in male social drinkers as a function of situationally induced depressive affect and anxiety. Psychopharmacology 65:251–257Google Scholar
  20. Prange AJ, Wilson IC, Lynn CW, Alltop LB, Stikeleather RA (1974) l-Tryptophan in mania: contribution to a permissive hypothesis of affective disorders. Arch Gen Psychiatry 30:56–62Google Scholar
  21. Sedvall G, Fyrö B, Gullberg B, Nybäack H, Wiesel FA, Wode-Helgodt B (1980) Relationships in healthy volunteers between concentrations of monoamine metabolites in cerebrospinal fluid and family history of psychiatric morbidity. Br J Psychiatry 136:366–374Google Scholar
  22. Shenker LJ (1980) Selective attention to dysphoric stimuli by depressed and non-depressed individuals. Ph D Thesis, McGill University, MontrealGoogle Scholar
  23. Schachter S, Rodin J (1974) Obese humans and rats. Erlbaum Halstead, Washington, DCGoogle Scholar
  24. Shopsin B, Gershon S, Goldstein M, Friedman E, Wilk S (1975) Use of synthesis inhibitors in defining a role of biogenic amines during imipramine treatment in depressed patients. Psychopharmacol Commun 1:239–249Google Scholar
  25. Shopsin B, Friedman E, Gershon S (1976) Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Arch Gen Psychiatry 33:811–819Google Scholar
  26. Smith B, Prockop DJ (1962) Central-nervous-system effects of ingestion of L-tryptophan by normal subjects. New Engl J Med 267:1338–1341Google Scholar
  27. Träskman-Bendz L, Asberg M, Bertilsson L, Thoren P (1984) CSF monoamine metabolites of depressed patients during illness and after recovery. Acta Psychiatr Scand 69:333–342Google Scholar
  28. van Praag HM (1977) Significance of biochemical parameters in the diagnosis, treatment and prevention of depressive disorders. Biol Psychiatry 12:101–131Google Scholar
  29. van Praag HM (1981) Management of depression with serotonin precursors. Biol Psychiatry 16:291–310Google Scholar
  30. van Praag HM, de Haan S (1979) Central serotonin metabolism and frequency of depression. Psychiatr Res 1:219–224Google Scholar
  31. Young SN, Gauthier S (1981) Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid. J Neurol Neurosurg Psychiatry 44:323–328Google Scholar
  32. Young SN, Anderson GM (1982) Factors influencing melatonin, 5-hydroxytryptophol, 5-hydroxyindoleacetic acid, 5-hydroxytryptamine and tryptophan in rat pineal glands. Neuroendocrinology 35:464–468Google Scholar
  33. Young SN, Gauthier S, Anderson GM, Purdy WC (1980) Tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human cerebrospinal fluid: interrelationships and the influence of age, sex, epilepsy and anticonvulsant drugs. J Neurol Neurosurg Psychiatry 43:438–445Google Scholar
  34. Zuckerman M, Lubin B (1965) Manual for the Multiple Affect Adjective Checklist. Education and Industrial Testing Service, San DiegoGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Simon N. Young
    • 1
  • Scott E. Smith
    • 2
  • Robert O. Pihl
    • 1
    • 2
  • Frank R. Ervin
    • 1
  1. 1.Department of PsychiatryMcGill UniversityMontrealCanada
  2. 2.Department of PsychologyMcGill UniversityMontrealCanada

Personalised recommendations