Photoperiodic and circadian bifurcation theories of depression and mania

Daniel F. Kripke, Jeffrey A. Elliott, David K. Welsh, Shawn Youngstedt

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Seasonal effects on mood have been observed throughout much of human history. Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight). We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion. The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones. Pituitary hormones largely mediate seasonal physiologic and behavioral variations. As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year. Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression. Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania. We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania. Much further research will be needed to add substance to these theories.

Original languageEnglish (US)
Article number107
StatePublished - May 6 2015

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • Pharmacology, Toxicology and Pharmaceutics(all)


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