The circadian basis of winter depression

Proc Natl Acad Sci U S A. 2006 May 9;103(19):7414-9. doi: 10.1073/pnas.0602425103. Epub 2006 Apr 28.


The following test of the circadian phase-shift hypothesis for patients with winter depression (seasonal affective disorder, or SAD) uses low-dose melatonin administration in the morning or afternoon/evening to induce phase delays or phase advances, respectively, without causing sleepiness. Correlations between depression ratings and circadian phase revealed a therapeutic window for optimal alignment of circadian rhythms that also appears to be useful for phase-typing SAD patients for the purpose of administering treatment at the correct time. These analyses also provide estimates of the circadian component of SAD that may apply to the antidepressant mechanism of action of appropriately timed bright light exposure, the treatment of choice. SAD may be the first psychiatric disorder in which a physiological marker correlates with symptom severity before, and in the course of, treatment in the same patients. The findings support the phase-shift hypothesis for SAD, as well as suggest a way to assess the circadian component of other psychiatric, sleep, and chronobiologic disorders.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Female
  • Humans
  • Male
  • Melatonin / metabolism
  • Melatonin / pharmacology
  • Middle Aged
  • Seasonal Affective Disorder / drug therapy
  • Seasonal Affective Disorder / metabolism
  • Seasonal Affective Disorder / pathology
  • Seasonal Affective Disorder / physiopathology*


  • Biomarkers
  • Melatonin