The phase shift hypothesis for the circadian component of winter depression

Alfred J. Lewy, Jennifer N. Rough, Jeannine B. Songer, Neelam Mishra, Krista Yuhas, Jonathan S. Emens

Research output: Contribution to journalReview articlepeer-review

87 Scopus citations


The finding that bright light can suppress melatonin production led to the study of two situations, indeed, models, of light deprivation: totally blind people and winter depressives. The leading hypothesis for winter depression (seasonal affective disorder, or SAD) is the phase shift hypothesis (PSH). The PSH was recently established in a study in which SAD patients were given low-dose melatonin in the afternoon/evening to cause phase advances, or in the morning to cause phase delays, or placebo. The prototypical phase-delayed patient, as well as the smaller subgroup of phase-advanced patients, optimally responded to melatonin given at the correct time. Symptom severity improved as circadian misalignment was corrected. Circadian misalignment is best measured as the time interval between the dim light melatonin onset (DLMO) and mid-sleep. Using the operational definition of the plasma DLMO as the interpolated time when melatonin levels continuously rise above the threshold of 10 pglmL, the average interval between DLMO and mid-sleep in healthy controls is 6 hours, which is associated with optimal mood in SAD patients.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalDialogues in Clinical Neuroscience
Issue number3
StatePublished - 2007
Externally publishedYes


  • Circadian rhythm
  • Dim light melatonin onset
  • Light
  • Melatonin
  • Phase angle difference
  • Seasonal affective disorder
  • Winter depression

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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