Effects of tryptophan depletion on drug-free patients with seasonal affective disorder during a stable response to bright light therapy

Arch Gen Psychiatry. 1997 Feb;54(2):133-8. doi: 10.1001/archpsyc.1997.01830140043008.


Background: A dysfunction of the serotonin system may play a major role in the pathogenesis of seasonal affective disorder. Bright light therapy has been shown to be effective in the treatment of winter depression in patients with seasonal affective disorder. Light therapy-induced remission from depression may be associated with changes in brain serotonin function.

Methods: After at least 2 weeks of clinical remission, 12 drug-free patients who had had depression with seasonal affective disorder underwent tryptophan depletion in a double-blind, placebo-controlled, balanced cross-over design study.

Results: Short-term tryptophan depletion induced a significant decrease in plasma free and total tryptophan levels (P < .001 for both, repeated measures analysis of variance), with peak effects occurring 5 hours after ingestion of a tryptophan-free amino acid drink. It emerged that tryptophan depletion leads to a transient depressive relapse, which was most pronounced on the day after the tryptophan-depletion testing. No clinically relevant mood changes were observed in the control testing.

Conclusions: The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. Our results suggest that the serotonin system might be involved in the mechanism of action of light therapy.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acids / administration & dosage
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phototherapy*
  • Placebos
  • Recurrence
  • Seasonal Affective Disorder / physiopathology*
  • Seasonal Affective Disorder / therapy*
  • Serotonin / biosynthesis
  • Serotonin / physiology*
  • Treatment Outcome
  • Tryptophan / administration & dosage
  • Tryptophan / deficiency*
  • Tryptophan / metabolism


  • Amino Acids
  • Placebos
  • Serotonin
  • Tryptophan