Psychopharmacology

, Volume 178, Issue 1, pp 92–99 | Cite as

Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers

  • E. A. T. Evers
  • D. E. Tillie
  • F. M. van der Veen
  • C. K. Lieben
  • J. Jolles
  • N. E. P. Deutz
  • J. A. J. Schmitt
Original Investigation

Abstract

Rationale

Disorders associated with low levels of serotonin (5-HT) are characterized by mood and cognitive disturbances. Acute tryptophan depletion (ATD) is an established method for lowering 5-HT levels and an important tool to study the effects of reduced 5-HT on mood and cognition in human subjects. The traditional ATD method, i.e., administration of separate amino acids (AAs), has several disadvantages. The AA mixture is costly, unpalatable and associated with gastrointestinal discomfort.

Objectives

The University of Maastricht developed a new and inexpensive method for ATD: a natural collagen protein (CP) mixture with low tryptophan (TRP) content. The reductions in plasma TRP after taking this CP mixture were compared with the reductions achieved taking the traditional AA mixture, and effects on memory and reversal learning were studied.

Methods

Fifteen healthy young volunteers participated in a double-blind, counterbalanced within-subject study. Reversal learning, verbal memory and pattern recognition were assessed at baseline and 3–4 h after taking the CP mixture.

Results

The new ATD method significantly reduced plasma TRP by 74% and the ratio between TRP and the other large AAs (TRP/LNAA) by 82%. The placebo mixture did not change these measures. Delayed recognition reaction time on the verbal learning task was increased following ATD. No other cognitive effects were found.

Conclusions

The CP mixture was shown to be an efficient tool for lowering plasma TRP in humans. The validity of this method with regard to behavioral changes remains to be established in healthy, vulnerable and clinical populations.

Keywords

Serotonin Acute tryptophan depletion Memory Reversal learning Mood 

References

  1. Anderson IM, Richell RA, Bradshaw CM (2003) The effects of acutetryptophan depletion on probabilistic choice. J Psychopharmacol 17:3–7CrossRefGoogle Scholar
  2. Biggio G, Fadda F, Fanni P, Tagliamonte A, Gessa G (1974) Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5 hydroxyindolacetic by a tryptophan-free diet. Life Sci 14:1321–1329CrossRefPubMedGoogle Scholar
  3. Buhot M, Martin S, Segu L (2000) Role of serotonin in memory impairment. Ann Med 32:210–221PubMedGoogle Scholar
  4. Carpenter LL, Anderson GM, Pelton GH, Gudin JA, Kirwin PD, Price LH, Heninger GR, McDougle CJ (1998) Tryptophan depletion during continuous CSF sampling in healthy human volunteers. Neuropsychopharmacology 19:26–35CrossRefPubMedGoogle Scholar
  5. Danjou P, Hamon M, Lacomblez L, Warot D (1990) Psychomotor, subjective and neuroendocrine effects of acute tryptophan depletion in the healthy volunteer. Psychiatry Psychobiol 5:31–38Google Scholar
  6. van der Does AJ (2001) The effects of tryptophan depletion on mood and psychiatric symptoms (review). J Affect Disord 64:107–119CrossRefPubMedGoogle Scholar
  7. van Eijk HM, Rooyakkers DR, Deutz NE (1993) Rapid routine in amino acids in plasma by high-performance liquid chromatography with a 2–3 microns spherisorb ODS ll column. J Chromatogr 620:143–148PubMedGoogle Scholar
  8. Elliott R, Sahakian BJ, Herrod JJ, Robbins TW, Paykel ES (1996) Neuropsychological impairments in unipolar depression: the influence of perceived failure on subsequent performance. Psychol Med 26:975–989PubMedGoogle Scholar
  9. Fadda F (2000) Tryptophan-free diets: a physiological tool to study brain serotonin function. News Physiol Sci 15:260–264PubMedGoogle Scholar
  10. Gallagher P, Massey AE, Young AH, McAllister-Williams RH (2003) Effects of acute tryptophan depletion on executive function in healthy volunteers. BMC Psychiatry 3:10CrossRefPubMedGoogle Scholar
  11. Gartside SE, Cowen PJ, Sharp T (1992) Effect of amino-acid loads on hippocampal 5-HT release in vivo evoked by electrical stimulation of the dorsal raphe nucleus and d-fenfluramine administration. Br J Pharmacol 107:448PGoogle Scholar
  12. Harrison BJ, Olver JS, Norman TR, Burrows GD, Wesnes KA, Nathan PJ (2004) Selective effects of acute serotonin and catecholamine depletion on memory in healthy women. J Psychopharmacol 18:32–40CrossRefPubMedGoogle Scholar
  13. Klaassen T, Riedel WJ, van Someren A, Deutz NE, Honig A, van Praag HM (1999) Mood effects of 24-hour tryptophan depletion in healthy first-degree relatives of patients with affective disorders. Biol Psychiatry 15:489–497CrossRefGoogle Scholar
  14. Lezak MD (1995) Neuropsychological assessment. Oxford University, New YorkGoogle Scholar
  15. Lieben CK, Blokland A, Westerink B, Deutz NE (2004) Acute tryptophan and serotonin depletion using an optimized tryptophan-free protein-carbohydrate mixture in the adult rat. Neurochem Int 44:9–16CrossRefPubMedGoogle Scholar
  16. Maes M, Meltzer HY (1995) Psychopharmacology: the fourth generation of progress. Psychopharmacology: the serotonin hypothesis of major depression. Raven, New YorkGoogle Scholar
  17. McNair DM, Lorr DM, Droppelman LF (1988) Manual for the profile of mood states. San Diego, CaliforniaGoogle Scholar
  18. Meneses A (1999) 5-HT system and cognition. Neurosci Biobehav Rev 23:1111–1125CrossRefPubMedGoogle Scholar
  19. Moja EA, Cipolla P, Castoldi D, Tofanetti O (1989) Dose-response decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats. Life Sci 44:971–976CrossRefPubMedGoogle Scholar
  20. Moore P, Landolt HP, Seifritz E, Clark C, Bhatti T, Kelsoe J, Rapaport M, Gillin JC (2000) Clinical and physiological consequences of rapid tryptophan depletion. Neuropsychopharmacology 23:601–622CrossRefPubMedGoogle Scholar
  21. Murphy FC, Sahakian BJ, Rubinsztein JS, Michael A, Rogers RD, Robbins TW, Paykel ES (1999) Emotional bias and inhibitory control processes in mania and depression. Psychol Med 29:1307–1321CrossRefPubMedGoogle Scholar
  22. Murphy FC, Smith KA, Cowen PJ, Robbins TW, Sahakian BJ (2002) The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacology 163:42–53CrossRefPubMedGoogle Scholar
  23. Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, De Montigny C, Blier P, Diksic M (1997) Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A 94:5308–5313CrossRefPubMedGoogle Scholar
  24. O’ Doherty J, Kringelbach ML, Rolls ET, Hornak J, Andrews C (2001) Abstract reward and punishment representations in the human orbitofrontal cortex. Nature 4:95–102Google Scholar
  25. Pollack I, Norman, DA (1964) A non-parametric analysis of recognition experiments. Psychon Sci 1:125–126Google Scholar
  26. Reilly JG, McTavish SF, Young AH (1997) Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. J Psychopharmacol 11:381–392PubMedGoogle Scholar
  27. Riedel W (2004) Cognitive changes after acute tryptophan depletion: what can they tell us? Psychol Med 34:3–8CrossRefPubMedGoogle Scholar
  28. Riedel WJ, Klaassen T, Deutz NEP, Someren van A, Praag van HM (1999) Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation. Psychopharmacology 141:362–369CrossRefPubMedGoogle Scholar
  29. Riedel WJ, Klaassen T, Schmitt JA (2002) Tryptophan, mood, and cognitive function (review). Brain Behav Immun 16:581–589CrossRefPubMedGoogle Scholar
  30. Rogers RD, Blackhaw AJ, Middleton HC, Matthews K, Hawtin H, Crowley C, Hopwood A, Wallace C, Deakin JFW, Sahakian BJ, Robbins TW (1999) Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology 146:482–491PubMedGoogle Scholar
  31. Rogers RD, Tunbridge EM, Bhagwagar Z, Drevets WC, Sahakian BJ, Carter CS (2003) Tryptophan depletion alters decision-making of healthy volunteers through altered processing of reward cues. Neuropsychopharmacology 28:153–162CrossRefPubMedGoogle Scholar
  32. Rubinsztein JS, Rogers RD, Riedel WJ, Mehta MA, Robbins TW, Sahakian BJ (2001) Acute tryptophan depletion impairs maintenance of “affective set” and delayed visual recognition in healthy volunteers. Springer, Berlin Heidelberg New YorkGoogle Scholar
  33. Schmitt JA, Jorissen BL, Sobzak S, van Boxtel MP, Hogervorst E, Deutz NE, Riedel WJ (2000) Tryptophan depletion impairs memory consolidation but improves focused attention in healthy young volunteers. J Psychopharmacol 14:21–29PubMedGoogle Scholar
  34. Sobczak S, Riedel WJ, Booij I, Aan Het Rot M, Deutz NE, Honig A (2002) Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers. Psychol Med 32:503–515CrossRefPubMedGoogle Scholar
  35. Teff KL, Young SN, Blundell JE (1989) The effect of protein or carbohydrate breakfasts on subsequent plasma amino acid levels, satiety and nutrient selection in normal males. Pharmacol Biochem Behav 34:829–837CrossRefPubMedGoogle Scholar
  36. Weltzin TE, Fernstrom MH, Kaye WH (1994) Serotonin and bulimia nervosa. Nutr Rev 52:399–408PubMedGoogle Scholar
  37. Williams WA, Shoaf SE, Hommer D, Rawlings R, Linnoila M (1999) Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers. J Neurochem 72:1641–1647CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • E. A. T. Evers
    • 1
  • D. E. Tillie
    • 1
  • F. M. van der Veen
    • 1
  • C. K. Lieben
    • 1
  • J. Jolles
    • 1
  • N. E. P. Deutz
    • 2
  • J. A. J. Schmitt
    • 1
  1. 1.Department of Psychiatry and Neuropsychology (DRT10), Brain and Behavior InstituteMaastricht UniversityMaastrichtThe Netherlands
  2. 2.Department of SurgeryMaastricht UniversityMaastrichtThe Netherlands

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