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.
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References
Beck AT (1976) Cognitive therapy and the emotional disorders. International Universities Press, New York
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 14:1321–1329
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 47–66
Coppen AJ (1967) The biochemistry of affective disorders. Br J Psychiatry 113:1237–1264
Coppen A, Prange AJ, Whybrow PC, Noguera R (1972) Abnormalities of indoleamines in affective disorders. Arch Gen Psychiatry 26:474–478
Cremata VY, Koe BK (1966) Clinical-pharmacological evaluation of p-chlorophenylalanine: a new serotonin-depleting agent. Clin Pharmacol Ther 7:768–776
Denckla WD, Dewey HK (1967) The determination of tryptophan in plasma, liver and urine. J Lab Clin Med 69:160–169
Engelman K, Lovenberg W, Sjoerdsma A (1967) Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome. New Engl J Med 227:1103–1108
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 22:869–870
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-405S
Greenwood MH, Lader MH, Kantameneni BD, Curzon G (1975) The acute effects of oral (-)-tryptophan in human subjects. Br J Clin Pharmacol 2:165–172
Lapin IP, Oxenkrug GF (1969) Intensification of the central serotonergic process as a possible determinant of the thymoleptic effect. Lancet i:132–136
Lehmann J (1982) Tryptophan deficiency stupor — a new psychiatric syndrome. Acta Psychiatr Scand Suppl 300:1–57
Lieberman HR, Corkin S, Spring BJ, Growdon JH, Wurtman RJ (1983) Mood, performance, and pain sensitivity: changes induced by food constituents. J Psychiatr Res 17:135–145
Munro HN (1968) Role of amino acid supply in regulating ribosome function. Fed Proc 27:1231–1237
Murphy DL, Campbell IC, Costa JL (1978) The brain serotonergic system in the affective disorders. Prog Neuro-Psychopharmacol 2:1–31
Oldendorf WH, Szabo J (1976) Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am J Physiol 230:94–98
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 248:693–695
Pihl RO, Yankofsky L (1979) Alcohol consumption in male social drinkers as a function of situationally induced depressive affect and anxiety. Psychopharmacology 65:251–257
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 30:56–62
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 136:366–374
Shenker LJ (1980) Selective attention to dysphoric stimuli by depressed and non-depressed individuals. Ph D Thesis, McGill University, Montreal
Schachter S, Rodin J (1974) Obese humans and rats. Erlbaum Halstead, Washington, DC
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 1:239–249
Shopsin B, Friedman E, Gershon S (1976) Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Arch Gen Psychiatry 33:811–819
Smith B, Prockop DJ (1962) Central-nervous-system effects of ingestion of L-tryptophan by normal subjects. New Engl J Med 267:1338–1341
Träskman-Bendz L, Asberg M, Bertilsson L, Thoren P (1984) CSF monoamine metabolites of depressed patients during illness and after recovery. Acta Psychiatr Scand 69:333–342
van Praag HM (1977) Significance of biochemical parameters in the diagnosis, treatment and prevention of depressive disorders. Biol Psychiatry 12:101–131
van Praag HM (1981) Management of depression with serotonin precursors. Biol Psychiatry 16:291–310
van Praag HM, de Haan S (1979) Central serotonin metabolism and frequency of depression. Psychiatr Res 1:219–224
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 44:323–328
Young SN, Anderson GM (1982) Factors influencing melatonin, 5-hydroxytryptophol, 5-hydroxyindoleacetic acid, 5-hydroxytryptamine and tryptophan in rat pineal glands. Neuroendocrinology 35:464–468
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 43:438–445
Zuckerman M, Lubin B (1965) Manual for the Multiple Affect Adjective Checklist. Education and Industrial Testing Service, San Diego
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Young, S.N., Smith, S.E., Pihl, R.O. et al. Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology 87, 173–177 (1985). https://doi.org/10.1007/BF00431803
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DOI: https://doi.org/10.1007/BF00431803