The Tryptophan Depletion Test: Impact on Sleep in Healthy Subjects and Patients with Obsessive—Compulsive Disorder

  • Ch. Huwig-Poppe
  • U. Voderholzer
  • J. Backhaus
  • D. Riemann
  • A. König
  • F. Hohagen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 467)

Abstract

The tryptophan depletion test is a research tool to study the functional consequences of decreasing the brain serotonin metabolism. Since serotonin is involved in sleep regulation and assumed to be of high importance in the etiology of psychiatric disorders, the acute polysomnographic effects of tryptophan depletion were studied in healthy subjects and patients with obsessive compulsive disorder (OCD). According to the reciprocal interaction model of non-REM and REM-sleep regulation we expected that tryptophan depletion in healthy controls should provoke alterations of sleep similar to depression, whereas we assumed that these effects would be more pronounced in patients with OCD.

Methods: 12 healthy subjects with a mean age of 34 years and 12 patients suffering from OCD with a mean age of 30 years had 4 polysomnographic investigations. After 1 adaption and 1 baseline night subjects received a low proteine diet on day 3 and 4 until midday. On day 4 at 18.00h subjects ingested an aminoacid mixture devoid of tryptophan. This procedure resulted in a decrease of 85% in healthy subjects and 80% in OCD patients at 22.00 h.

Results: The tryptophan depletion led to more pronounced disturbances of sleep continuity in OCD patients than in healthy subjects in terms of an increase of wake time and a decrease of total sleep time. In both groups a decrease of sleep stage 2 could be observed. Healthy subjects showed significant alterations of phasic REM parameters as REM density and total number of rapid eye movements, what was not the case for OCD patients.

Conclusions: Our results indicate the important role of the serotonergic system for sleep maintainance and the phasic aspects of REM sleep. Furthermore our data demonstrate that the tryptophan depletion test is a useful tool to evaluate the hypothesis of a serotonergic involvement in sleep regulation and the etiology of psychiatric disorders.

Keywords

Depression Cystein Serotonin Tryptophan Melatonin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barr, L., Goodman, W.K., McDougle, C.L., Delgado, P.L., Heninger, G.R., Charney, D.S., and Price, L.H., 1994, Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors, Arch. Gen. Psychiatry, 51:309–317.PubMedCrossRefGoogle Scholar
  2. Bebbington, P.E., 1998, Epidemiology of obsessive and compulsive disorder, Brit. J. Psychiatry, 173(suppl. 35), 2–6.Google Scholar
  3. Benkelfat, C., Ellenbogen, M., Dean, P., Palmour, R., and Young, S., 1994, Mood Lowering Effect of Tryptophan Depletion, Arch. Gen. Psychiatry, 51:687–697.PubMedCrossRefGoogle Scholar
  4. Berger, M. and Riemann, D., 1993, REM sleep in depression—an overview. J. Sleep Res., 2:211–223.PubMedCrossRefGoogle Scholar
  5. Bhatti, T., Gillin, C., Seifritz, Moore, P., Clark, C., Golshan, S., Stahl, S., Rapaport, M., and Kelsoe, 1998, Effects of a Tryptophan-Free Amino Acid Drink Challenge on Normal Human Sleep Electroencephalogram and Mood, Biol. Psychiatry, 43:52–59.PubMedCrossRefGoogle Scholar
  6. Delgado, P., Charney, D., Price, L., Aghajanian, G., Landis, H., and Heninger, G., 1990, Serotonin and the Mechanism of Antidepressant Action, Arch. Gen. Psychiatry, 47:411–418.PubMedCrossRefGoogle Scholar
  7. Goodman, W.K., Price, L.H., Rasmussen, S.A., Mazure, C., Fleischmann, R.L., Hill, C.L., Heninger, G.R., and Charney, D.S., 1989, The Yale-Brown-Obsessive Compulsive Scale: I. Development, use and reliability, A rch. Gen. Psychiatry, 46:1012–1016.CrossRefGoogle Scholar
  8. Greist, J.H., Jefferson, J.W., and Kobak, K.A., 1995, Efficacy and tolerability of serotonin transport inhibitors in obsessive compulsive disorder: a meta-analysis. Arch. Gen. Psychiatry, 52, 53–60.PubMedCrossRefGoogle Scholar
  9. Hobson, J.A., Lydic, R., and Baghdoyan, H.A., 1986, Evolving concepts of sleep-wake-cycle generation: From brain centers to neuronal populations. Behavioral Brain Sciences 9:371–448.CrossRefGoogle Scholar
  10. Hohagen, F., Lis, S., Krieger, S., Winkelmann, G., Riemann, D., Fritsch-Montero, R., Reye, E., Aldenhoff, J., and Berger, M., 1994, Sleep EEG of patients with obsessive-compulsive disorder, Eur. Arch. Psychiatry Clin. Neurosci., 243:273–278.PubMedCrossRefGoogle Scholar
  11. Insel, T.R., Gillin, J.C., Moore, A., Mendelson, W.B., Loewnstein, R., and Murphy, D.L., 1982, Sleep in obsessive-compulsive disorder, Arch. Gen. Psychiatry, 93:1372–1377.CrossRefGoogle Scholar
  12. Jouvet, M., 1972, The role of monoamine and acetylcholine-containing neurons in the regulation of the sleep-waking cycle, Ergebn. Physiol., 64:166–307.PubMedGoogle Scholar
  13. Leonard, C.S. and Llinas, R., 1994, Serotonergic and cholinergic inhibition of mesopontine cholinergic neurons controlling REM sleep: an in vitro electrophysiological study, Neuroscience, 59:309–330.PubMedCrossRefGoogle Scholar
  14. Moja, E.A., Antinoro, E., Cesa-Bianchi, M., and Gessa, G.L., 1984, Increase in stage 4 sleep after ingestion of a tryptophan free diet in humans, Pharmacological Research Communications, 16:909–914.PubMedCrossRefGoogle Scholar
  15. Rechtschaffen, A. and Kales, A. (eds.), 1968, A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Department of Health, Education and Welfare, Washington DC.Google Scholar
  16. Schneider-Helmert D. and Spinweber C.L., 1986, Evaluation of 1-tryptophan for treatment of insomnia: A review, Psychopharmacology, 89:1–7.PubMedCrossRefGoogle Scholar
  17. Shouse, M.N. and Siegel, J.M., 1992, Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep, Brain Research, 571:50–63.PubMedCrossRefGoogle Scholar
  18. Smeraldi, E., Diaferia, G., Erzegovesi, S., Lucca, A., Bellodi, L., and Moja, E., 1996, Tryptophan depletion in obsessive-compulsive patients, Biol. Psychiatry, 40:398–402.PubMedCrossRefGoogle Scholar
  19. Voderholzer, U., Riemann, D., Backhaus, J., König, A., Böhme, R., Kiemen, A., Berger, M., and Hohagen, F., 1996, Polysomnographic studies in patients with obsessive-compulsive disorder, J. Sleep Research, 5,suppl 1, 246.Google Scholar
  20. Walsleben, J., Robinson, D., Lemus, C., Hackshaw, R., Norman, R., and Alvir, J., 1990, Polysomnographic aspects of obsessive-compulsive disorders, Sleep Res., 19:177.Google Scholar
  21. Wu M.F. and Siegel J.M., 1990, Facilitation of the acoustic startle reflex by ponto-geniculo-occipital waves: Effects of PCPA. Brain Res., 532:237–241.PubMedCrossRefGoogle Scholar
  22. Young, S.N., Smith, S.E., Pihl, R.O., and Ervin, F.R., 1985, Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology, 87:173–177.PubMedCrossRefGoogle Scholar
  23. Zerssen von D., 1986, Clinical Self-Rating Scales (CSRS) of the Munich Psychiatry Information System (PSYCHIS München). In: Sartorius N. and Ban T.A. (eds.), Assessment of Depression. Springer-Verlag, Berlin, pp 270–303.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Ch. Huwig-Poppe
    • 1
  • U. Voderholzer
    • 1
  • J. Backhaus
    • 1
  • D. Riemann
    • 1
  • A. König
    • 1
  • F. Hohagen
    • 1
  1. 1.Department of Psychiatry and PsychotherapyUniversity of FreiburgFreiburgGermany

Personalised recommendations