Skip to main content
SpringerLink
Log in

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

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Anderson IM, Richell RA, Bradshaw CM (2003) The effects of acutetryptophan depletion on probabilistic choice. J Psychopharmacol 17:3–7

    Article  CAS  Google Scholar 

  • 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 14:1321–1329

    Article  CAS  PubMed  Google Scholar 

  • Buhot M, Martin S, Segu L (2000) Role of serotonin in memory impairment. Ann Med 32:210–221

    CAS  PubMed  Google Scholar 

  • 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 19:26–35

    Article  CAS  PubMed  Google Scholar 

  • Danjou P, Hamon M, Lacomblez L, Warot D (1990) Psychomotor, subjective and neuroendocrine effects of acute tryptophan depletion in the healthy volunteer. Psychiatry Psychobiol 5:31–38

    Google Scholar 

  • van der Does AJ (2001) The effects of tryptophan depletion on mood and psychiatric symptoms (review). J Affect Disord 64:107–119

    Article  PubMed  Google Scholar 

  • 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 620:143–148

    PubMed  Google Scholar 

  • 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 26:975–989

    CAS  PubMed  Google Scholar 

  • Fadda F (2000) Tryptophan-free diets: a physiological tool to study brain serotonin function. News Physiol Sci 15:260–264

    CAS  PubMed  Google Scholar 

  • Gallagher P, Massey AE, Young AH, McAllister-Williams RH (2003) Effects of acute tryptophan depletion on executive function in healthy volunteers. BMC Psychiatry 3:10

    Article  PubMed  Google Scholar 

  • 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 107:448P

    Google Scholar 

  • 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 18:32–40

    Article  CAS  PubMed  Google Scholar 

  • 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 15:489–497

    Article  Google Scholar 

  • Lezak MD (1995) Neuropsychological assessment. Oxford University, New York

  • 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 44:9–16

    Article  CAS  PubMed  Google Scholar 

  • Maes M, Meltzer HY (1995) Psychopharmacology: the fourth generation of progress. Psychopharmacology: the serotonin hypothesis of major depression. Raven, New York

  • McNair DM, Lorr DM, Droppelman LF (1988) Manual for the profile of mood states. San Diego, California

  • Meneses A (1999) 5-HT system and cognition. Neurosci Biobehav Rev 23:1111–1125

    Article  CAS  PubMed  Google Scholar 

  • 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 44:971–976

    Article  CAS  PubMed  Google Scholar 

  • 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 23:601–622

    Article  CAS  PubMed  Google Scholar 

  • 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 29:1307–1321

    Article  CAS  PubMed  Google Scholar 

  • 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 163:42–53

    Article  CAS  PubMed  Google Scholar 

  • 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 94:5308–5313

    Article  CAS  PubMed  Google Scholar 

  • O’ Doherty J, Kringelbach ML, Rolls ET, Hornak J, Andrews C (2001) Abstract reward and punishment representations in the human orbitofrontal cortex. Nature 4:95–102

    Google Scholar 

  • Pollack I, Norman, DA (1964) A non-parametric analysis of recognition experiments. Psychon Sci 1:125–126

    Google Scholar 

  • Reilly JG, McTavish SF, Young AH (1997) Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. J Psychopharmacol 11:381–392

    CAS  PubMed  Google Scholar 

  • Riedel W (2004) Cognitive changes after acute tryptophan depletion: what can they tell us? Psychol Med 34:3–8

    Article  PubMed  Google Scholar 

  • 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 141:362–369

    Article  CAS  PubMed  Google Scholar 

  • Riedel WJ, Klaassen T, Schmitt JA (2002) Tryptophan, mood, and cognitive function (review). Brain Behav Immun 16:581–589

    Article  CAS  PubMed  Google Scholar 

  • 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 146:482–491

    CAS  PubMed  Google Scholar 

  • 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 28:153–162

    Article  CAS  PubMed  Google Scholar 

  • 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 York

  • 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 14:21–29

    CAS  PubMed  Google Scholar 

  • 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 32:503–515

    Article  CAS  PubMed  Google Scholar 

  • 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 34:829–837

    Article  CAS  PubMed  Google Scholar 

  • Weltzin TE, Fernstrom MH, Kaye WH (1994) Serotonin and bulimia nervosa. Nutr Rev 52:399–408

    CAS  PubMed  Google Scholar 

  • 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 72:1641–1647

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

E. A. T. Evers, F. M. van der Veen and J. Jolles are funded by the ZonMW grant 912-02-050.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Neuropsychology (DRT10), Brain and Behavior Institute, Maastricht University, P.O. Box 616, Maastricht, 6200, The Netherlands

    E. A. T. Evers, D. E. Tillie, F. M. van der Veen, C. K. Lieben, J. Jolles & J. A. J. Schmitt

  2. Department of Surgery, Maastricht University, Maastricht, 6200, The Netherlands

    N. E. P. Deutz

Authors
  1. E. A. T. Evers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. E. Tillie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. M. van der Veen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. K. Lieben
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Jolles
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. E. P. Deutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. A. J. Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. A. T. Evers.

Additional information

This article was originally published under the DOI 10.1007/s00213-004-1933-4. Unfortunately an unrelated paper appeared in print and in the PDF version online. For this reason, all versions of the correct article are now published here under the new DOI, 10.1007/s00213-004-2141-y.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Evers, E.A.T., Tillie, D.E., van der Veen, F.M. et al. Effects of a novel method of acute tryptophan depletion on plasma tryptophan and cognitive performance in healthy volunteers. Psychopharmacology 178, 92–99 (2005). https://doi.org/10.1007/s00213-004-2141-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-004-2141-y

Keywords

Search

Navigation