The circadian basis of winter depression

Alfred J. Lewy, Bryan J. Lefler, Jonathan S. Emens, Vance K. Bauer

Research output: Contribution to journalArticlepeer-review

353 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7414-7419
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - May 9 2006


  • Chronobiology
  • Circadian rhythms
  • Dim light melatonin onset (DLMO)
  • Melatonin
  • Seasonal affective disorder

ASJC Scopus subject areas

  • General


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