Original Contribution | Published:

Functional GI Disorders

Acute Tryptophan Depletion Alters Gastrointestinal and Anxiety Symptoms in Irritable Bowel Syndrome

The American Journal of Gastroenterology volume 101, pages 25822587 (2006) | Download Citation




To assess the effect of acute changes in serotonin (5-HT) synthesis using the acute tryptophan depletion (ATD) paradigm on gastrointestinal (GI) and mood symptoms in irritable bowel syndrome (IBS).


In a randomized double-blind crossover study, 29 subjects (18 patients with ROME II defined IBS and 11 age-matched controls) were studied under ATD and acute tryptophan increase (ATI) conditions. GI symptoms, mood and anxiety ratings, as well as plasma tryptophan concentrations were measured.


Total (and free) plasma tryptophan concentrations decreased on the ATD day in patients (73% [82%]) and controls (73% [80%]), and increased on the ATI day in patients (59% [143%]) and controls (61% [381%]). Compared with the ATD day, IBS patients reported more GI symptoms on the ATI day at +210 (p < 0.001) and at +270 (p < 0.05) min post drink. IBS patients also reported less anxiety on the ATI day compared with the ATD day at +270 min (p < 0.001). ATD and ATI did not affect these ratings in control participants. IBS patients had a lower mood compared with controls (p < 0.05), but this did not differ between the ATI and ATD days in either group.


IBS patients' GI and anxiety responses to changes in tryptophan load differ from controls. This suggests a difference in serotonergic functioning between these two groups and provides evidence to support the hypothesis that 5-HT dysfunction is involved in IBS.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    , , . The epidemiology of irritable bowel syndrome in North America: Systematic review. Am J Gastroenterol 2002;97:1910–1915.

  2. 2.

    . Irritable bowel syndrome, anxiety, and depression: What are the links? J Clin Psychiatry 2001;62(suppl 8):38–45.

  3. 3.

    , , . Medically unexplained physical symptoms, anxiety, and depression: A meta-analytic review. Psychosom Med 2003;65:528–533.

  4. 4.

    , . The role of serotonin in human mood and social interaction. Insight from altered tryptophan levels. Pharmacol Biochem Behav 2002;71:857–865.

  5. 5.

    . Role of serotonin in the athophysiology of the irritable bowel syndrome. Br J Pharmacol 2004;141:1285–1293.

  6. 6.

    . 5-Hydroxytryptamine in the physiology of the bowel. Aliment Pharmacol Ther 1999;13(suppl 2):15–30.

  7. 7.

    . Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectrums 2005;10:49–56.

  8. 8.

    . Rationale for using serotonergic agents to treat irritable bowel syndrome. Am J Health Syst Pharm 2005; 62:700–711.

  9. 9.

    , , , et al. Does a preexisting anxiety disorder predict response to paroxetine in irritable bowel syndrome? Psychosomatics 2002;43:451–455.

  10. 10.

    , , . Acute tryptophan depletion. Part I: Rationale and methodology. Aust N Z J Psychiatry 2005;39:558–564.

  11. 11.

    , , . Acute tryptophan depletion. Part II: Clinical effects and implications. Aust N Z J Psychiatry 2005;39:565–574.

  12. 12.

    , , . Monoamine depletion in psychiatric and healthy populations: Review. Mol Psychiatry 2003;8:951–973.

  13. 13.

    , , , et al. Tryptophan depletion during continuous CSF sampling in healthy human subjects. Neuropsychopharmacology 1998;19:26–35.

  14. 14.

    , , , et al. Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers. J Neurochem 1999;72:1641–1647.

  15. 15.

    , , , et al. Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls. Gut 2004;53:1794–1800.

  16. 16.

    , , , et al. Predictors of mood response to acute tryptophan depletion. A reanalysis. Neuropsychopharmacology 2002;27:852–861.

  17. 17.

    , , , et al. Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine. J Psychopharmacol 2002;16:5–14.

  18. 18.

    , , , et al. Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder. Biol Psychiatry 2004;56:503–509.

  19. 19.

    , , . Relapse of depression after rapid depletion of tryptophan. Lancet 1997;349:915–919.

  20. 20.

    , , . Physiological and psychological measures in anxious patients. Psychol Med 1974;4:364–373.

  21. 21.

    . Manual for the State Trait Anxiety Inventory (STAI). Consulting Psychologists Press, Palo Alto, CA, 1983.

  22. 22.

    , , , et al. Self-reported depressive symptoms that differentiate recurrent-episode major depression from dysthymic disorders. J Clin Psychol 1987;43:246–250.

  23. 23.

    , . Power and sample size calculations. A review and computer program. Control Clin Trials 1990;11:116–128.

  24. 24.

    , . The continuing problem of false positives in repeated measures ANOVA in psychophysiology: A multivariate solution. Psychophysiology 1987;24:479–86.

  25. 25.

    , , , et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001;15:1655–1666.

  26. 26.

    , , , et al. Efficacy and safety of alosetron in women with irritable bowel syndrome: A randomised, placebo-controlled trial. Lancet 2000;355:1035–1040.

  27. 27.

    , , , et al. A controlled cross-over study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 2006; Doi:.

  28. 28.

    , , , et al. Open-label treatment with citalopram in patients with irritable bowel syndrome: A pilot study. Prim Care Companion J Clin Psychiatry 2005;7:162–166.

  29. 29.

    , , , et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women. Gut 2004;53:1452–1458.

  30. 30.

    , , , et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996;66:2621–2624.

  31. 31.

    , , , et al. Does depression influence symptom severity in irritable bowel syndrome? Case study of a patient with irritable bowel syndrome and bipolar disorder. Psychosom Med 2003;65:919–923.

  32. 32.

    , , , et al. Inhalation of 35% CO(2) results in activation of the HPA axis in healthy volunteers. Psychoneuroendocrinology 2002;27:715–729.

  33. 33.

    , . A psychophysical evaluation of the relationship between trait anxiety, pain perception, and induced state anxiety. J Pain 2005;6:612–619.

  34. 34.

    , , , et al. Does a rectal barostat procedure induce stress in IBS patients and healthy controls? Eur J Gastroenterol Hepatol 2003;15:A38.

Download references


This study was funded by Avon and Wiltshire Partnership NHS Trust R and D. The sponsors had no role in study design, data collection, data analysis, data interpretation, or writing of the report. M Franklin performed the tryptophan assays. Thank you to C Rogers for statistical advice and A Rich for her help in completion of the study.

Author information


  1. Clinical Science at South Bristol, University of Bristol, Bristol, United Kingdom

    • Jonathan Shufflebotham
    •  & Chris Probert
  2. School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia

    • Sean Hood
  3. Bristol Royal Infirmary, Bristol, United Kingdom

    • Julie Hendry
  4. Psychopharmacology Unit, University of Bristol, Bristol, United Kingdom

    • Dana A Hince
    • , Kelly Morris
    • , David Nutt
    •  & John Potokar


  1. Search for Jonathan Shufflebotham in:

  2. Search for Sean Hood in:

  3. Search for Julie Hendry in:

  4. Search for Dana A Hince in:

  5. Search for Kelly Morris in:

  6. Search for David Nutt in:

  7. Search for Chris Probert in:

  8. Search for John Potokar in:

Corresponding author

Correspondence to John Potokar.

About this article

Publication history






Further reading