Tryptophan supplementation induces a positive bias in the processing of emotional material in healthy female volunteers

Abstract

Rationale

The serotonin precursor l-tryptophan (TRP) is available as a nutritional supplement and is licensed as an antidepressant in a number of countries. However, evidence of its efficacy as the primary treatment for depression is limited, and the direct action of TRP on the symptoms of depression and anxiety has not been well-characterised.

Objectives

The present study assessed whether TRP induces cognitive changes opposite to the negative biases found in depression and characteristic of those induced by serotonergic antidepressants in healthy volunteers.

Materials and methods

Thirty eight healthy volunteers were randomised to receive 14 days double-blind intervention with TRP (1 g 3× a day) or placebo. On the final day, emotional processing was assessed using four tasks: facial expression recognition, emotion-potentiated startle, attentional probe and emotional categorisation and memory.

Results

TRP increased the recognition of happy facial expressions and decreased the recognition of disgusted facial expressions in female, but not male, volunteers. TRP also reduced attentional vigilance towards negative words and decreased baseline startle responsivity in the females.

Conclusions

These findings provide evidence that TRP supplementation in women induces a positive bias in the processing of emotional material that is reminiscent of the actions of serotonergic antidepressants. This highlights a key role for serotonin in emotional processing and lends support to the use of TRP as a nutritional supplement in people with mild depression or for prevention in those at risk. Future studies are needed to clarify the effect of tryptophan on these measures in men.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

References

  1. Allen NB, Trinder J, Brennan C (1999) Affective startle modulation in clinical depression: preliminary findings. Biol Psychiatry 46:542–550

    PubMed  Article  CAS  Google Scholar 

  2. Anderson NH (1968) Likableness ratings of 555 personality-trait words. J Pers Soc Psychol 9:272–279

    PubMed  Article  CAS  Google Scholar 

  3. Attenburrow MJ, Williams C, Odontiadis J, Reed A, Powell J, Cowen PJ, Harmer CJ (2003) Acute administration of nutritionally sourced tryptophan increases fear recognition. Psychopharmacology (Berl) 169:104–107

    Article  CAS  Google Scholar 

  4. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    PubMed  CAS  Google Scholar 

  5. Beck AT, Rush AJ, Shaw BF, Emery G (1979) Cognitive therapy of depression. Guilford, New York

    Google Scholar 

  6. Benkelfat C, Ellenbogen MA, Dean P, Palmour RM, Young SN (1994) Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders. Arch Gen Psychiatry 51:687–697

    PubMed  CAS  Google Scholar 

  7. Bhagwagar Z, Cowen PJ, Goodwin GM, Harmer CJ (2004) Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. Am J Psychiatry 161:166–168

    PubMed  Article  Google Scholar 

  8. Booij L, Van der DW, Benkelfat C, Bremner JD, Cowen PJ, Fava M, Gillin C, Leyton M, Moore P, Smith KA, Van der Kloot WA (2002) Predictors of mood response to acute tryptophan depletion. A reanalysis. Neuropsychopharmacology 27:852–861

    PubMed  Article  CAS  Google Scholar 

  9. Bouhuys AL, Geerts E, Gordijn MC (1999) Depressed patients’ perceptions of facial emotions in depressed and remitted states are associated with relapse: a longitudinal study. J Nerv Ment Dis 187:595–602

    PubMed  Article  CAS  Google Scholar 

  10. Bradley BP, Mogg K, Millar N (1996) Implicit memory bias in clinical and non-clinical depression. Behav Res Ther 34:865–879

    PubMed  Article  CAS  Google Scholar 

  11. Bradley BP, Mogg K, Lee SC (1997) Attentional biases for negative information in induced and naturally occurring dysphoria. Behav Res Ther 35:911–927

    PubMed  Article  CAS  Google Scholar 

  12. Buss AH, Durkee A (1957) An inventory for assessing different kinds of hostility. J Consult Psychol 21:343–349

    PubMed  Article  CAS  Google Scholar 

  13. Coppen A, Shaw DM, Farrell JP (1963) Potentiation of the antidepressive effect of a monoamine-oxidase inhibitor by tryptophan. Lancet 1:79–81

    PubMed  Article  CAS  Google Scholar 

  14. Davis M, Shi C (1999) The extended amygdala: are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety? Ann N Y Acad Sci 877:281–291

    PubMed  Article  CAS  Google Scholar 

  15. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR (1990) Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 47:411–418

    PubMed  CAS  Google Scholar 

  16. Ekman P, Friesen WV (1976) Pictures of facial affect. Palo Alto, California

    Google Scholar 

  17. Ellenbogen MA, Young SN, Dean P, Palmour RM, Benkelfat C (1996) Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability. Neuropsychopharmacology 15:465–474

    PubMed  Article  CAS  Google Scholar 

  18. Glassman AH, Platman SR (1969) Potentiation of a monoamine oxidase inhibitor by tryptophan. J Psychiatr Res 7:83–88

    PubMed  Article  CAS  Google Scholar 

  19. Grillon C (2002) Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology. Biol Psychiatry 52:958–975

    PubMed  Article  Google Scholar 

  20. Grillon C, Ameli R, Goddard A, Woods SW, Davis M (1994) Baseline and fear-potentiated startle in panic disorder patients. Biol Psychiatry 35:431–439

    PubMed  Article  CAS  Google Scholar 

  21. Grillon C, Morgan CA III, Davis M, Southwick SM (1998) Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder. Biol Psychiatry 44:1027–1036

    PubMed  Article  CAS  Google Scholar 

  22. Grillon C, Warner V, Hille J, Merikangas KR, Bruder GE, Tenke CE, Nomura Y, Leite P, Weissman MM (2005) Families at high and low risk for depression: a three-generation startle study. Biol Psychiatry 57:953–960

    PubMed  Article  Google Scholar 

  23. Gur RC, Erwin RJ, Gur RE, Zwil AS, Heimberg C, Kraemer HC (1992) Facial emotion discrimination: II. Behavioral findings in depression. Psychiatry Res 42:241–251

    PubMed  Article  CAS  Google Scholar 

  24. Harmer CJ, Bhagwagar Z, Perrett DI, Vollm BA, Cowen PJ, Goodwin GM (2003) Acute SSRI administration affects the processing of social cues in healthy volunteers. Neuropsychopharmacology 28:148–152

    PubMed  Article  CAS  Google Scholar 

  25. Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM (2004) Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry 161:1256–1263

    PubMed  Article  Google Scholar 

  26. Harmer CJ, Mackay C, Reid CB, Cowen PJ, Goodwin GM (2006) Antidepressant drug treatment modifies the neural processing of non-conscious threat cues. Biol Psychiatry (epub ahead of publication)

  27. Hartmann E, Elion R (1977) The insomnia of ‘sleeping in a strange place’: effects of l-tryptophane. Psychopharmacology (Berl) 53:131–133

    Article  CAS  Google Scholar 

  28. Hayward G, Goodwin GM, Cowen PJ, Harmer CJ (2005) Low-dose tryptophan depletion in recovered depressed patients induces changes in cognitive processing without depressive symptoms. Biol Psychiatry 57:517–524

    PubMed  Article  CAS  Google Scholar 

  29. Knutson B, Wolkowitz OM, Cole SW, Chan T, Moore EA, Johnson RC, Terpstra J, Turner RA, Reus VI (1998) Selective alteration of personality and social behavior by serotonergic intervention. Am J Psychiatry 155:373–379

    PubMed  CAS  Google Scholar 

  30. Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Davis SM, Harrison WM, Keller MB (2001) Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry 157:1445–1452

    Article  Google Scholar 

  31. Lang PJ, Bradley MM, Cuthbert BN (1998) International Affective Picture System (IAPS): technical manual and affective ratings. Gainsville, University of Florida, Center for Research in Psychophysiology

  32. Larson CL, Ruffalo D, Nietert JY, Davidson RJ (2000) Temporal stability of the emotion-modulated startle response. Psychophysiology 37:92–101

    PubMed  Article  CAS  Google Scholar 

  33. MacLeod C, Mathews A, Tata P (1986) Attentional bias in emotional disorders. J Abnorm Psychol 95:15–20

    PubMed  Article  CAS  Google Scholar 

  34. Mogg K, Bradley BP, Williams R (1995) Attentional bias in anxiety and depression: the role of awareness. Br J Clin Psychol 34(Pt 1):17–36

    PubMed  Google Scholar 

  35. Moskowitz DS, Pinard G, Zuroff DC, Annable L, Young SN (2001) The effect of tryptophan on social interaction in everyday life: a placebo-controlled study. Neuropsychopharmacology 25:277–289

    PubMed  Article  CAS  Google Scholar 

  36. 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

    PubMed  Article  CAS  Google Scholar 

  37. 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 (Berl) 163:42–53

    Article  CAS  Google Scholar 

  38. Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de MC, 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

    PubMed  Article  CAS  Google Scholar 

  39. Pare CM (1963) Potentiation of monoamine-oxidase inhibitors by tryptophan. Lancet 35:527–528

    Article  Google Scholar 

  40. Pihl RO, Young SN, Harden P, Plotnick S, Chamberlain B, Ervin FR (1995) Acute effect of altered tryptophan levels and alcohol on aggression in normal human males. Psychopharmacology (Berl) 119:353–360

    Article  CAS  Google Scholar 

  41. Raleigh MJ, McGuire MT (1991) Bidirectional relationships between tryptophan and social behavior in vervet monkeys. Adv Exp Med Biol 294:289–298

    PubMed  CAS  Google Scholar 

  42. Raleigh MJ, Brammer GL, Yuwiler A, Flannery JW, McGuire MT, Geller E (1980) Serotonergic influences on the social behavior of vervet monkeys (Cercopithecus aethiops sabaeus). Exp Neurol 68:322–334

    PubMed  Article  CAS  Google Scholar 

  43. Raleigh MJ, McGuire MT, Brammer GL, Pollack DB, Yuwiler A (1991) Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys. Brain Res 559:181–190

    PubMed  Article  CAS  Google Scholar 

  44. Shaw K, Turner J, Del MC (2002) Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Aust N Z J Psychiatry 36:488–491

    PubMed  Article  Google Scholar 

  45. Smith KA, Fairburn CG, Cowen PJ (1997) Relapse of depression after rapid depletion of tryptophan. Lancet 349:915–919

    PubMed  Article  CAS  Google Scholar 

  46. Spielberger CD, Gorsuch RL, Lushene RD (1983) Manual for the State-Trait Anxiety Inventory (STAI). Consulting Psychologists, Palo Alto, California

  47. Surguladze SA, Young AW, Senior C, Brebion G, Travis MJ, Phillips ML (2004) Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression. Neuropsychology 18:212–218

    PubMed  Article  Google Scholar 

  48. Thomson J, Rankin H, Ashcroft GW, Yates CM, McQueen JK, Cummings SW (1982) The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline and a combination of L-tryptophan and amitriptyline with placebo. Psychol Med 12:741–751

    PubMed  CAS  Article  Google Scholar 

  49. von Zerssen D, Strian F, Schwarz D (1974) Evaluation of depressive states, especially in longitudinal studies. Mod Probl Pharmacopsychiatry 7:189–202

    Google Scholar 

  50. Walderhaug E, Lunde H, Nordvik JE, Landro NI, Refsum H, Magnusson A (2002) Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals. Psychopharmacology (Berl) 164:385–391

    Article  CAS  Google Scholar 

  51. Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54:1063–1070

    PubMed  Article  CAS  Google Scholar 

  52. Weisman AN, Beck AT (1978) Development and validation of the Dysfunctional Attitudes Scale: a preliminary investigation. Paper presented at the American Education Research Association conference. Toronto, Canada

  53. Young SN, Gauthier S (1981) Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid in human lumbar and cisternal cerebrospinal fluid. J Neurol Neorosurg Psychiatry 44:323–328

    CAS  Article  Google Scholar 

  54. Young SN, Smith SE, Pihl RO, Ervin FR (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology (Berl) 87:173–177

    Article  CAS  Google Scholar 

  55. Young AW, Rowland D, Calder AJ, Etcoff NL, Seth A, Perrett DI (1997) Facial expression megamix: tests of dimensional and category accounts of emotion recognition. Cognition 63:271–313

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgement

SM was supported by a Wellcome Trust studentship.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Catherine J. Harmer.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Murphy, S.E., Longhitano, C., Ayres, R.E. et al. Tryptophan supplementation induces a positive bias in the processing of emotional material in healthy female volunteers. Psychopharmacology 187, 121–130 (2006). https://doi.org/10.1007/s00213-006-0401-8

Download citation

Keywords

  • Tryptophan
  • Serotonin
  • Emotional processing
  • Depression
  • Facial expression recognition
  • Healthy volunteers