Association of circadian properties of temporal processing with rapid antidepressant response to wake and light therapy in bipolar disorder

Takuya Yoshiike, Sara Dallaspezia, Kenichi Kuriyama, Naoto Yamada, Cristina Colombo, Francesco Benedetti

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Temporal processing, crucial to guide behavior toward a goal, may have a role in forming a depressive episode, yet it remains unclear which properties of temporal processing are central to antidepressant response. Production of a short duration oscillates in a circadian manner. Altered circadian organization of physiology and behavior are a hallmark of bipolar disorder. We thus tested whether circadian dynamics of time production associate with treatment response in bipolar disorder. METHODS: Over the three cycles of total sleep deprivation combined with light therapy (chronotherapeutics) in one week, 20 inpatients with a major depressive episode in the course of bipolar disorder produced 10 s and rated their subjective mood and vigilance levels repeatedly. RESULTS: Eleven patients (58%) among 19 completers achieved remission. Produced time intervals (PTIs) fluctuated more synchronously with mood levels (r = -0.77) than vigilance levels (r = -0.59) during treatment. A higher degree of shortening of PTIs, but not changes in mood or vigilance levels, during the initial 24-h period of treatment predicted better response (LR χ2 = 4.58, P = 0.032). Strong opposite daily changes for PTIs and mood levels observed at baseline were both attenuated after treatment only in remitters (F = 7.25, P = 0.015). LIMITATIONS: Potential external confounders that affect time perception were not controlled. CONCLUSIONS: The results are the first to demonstrate an association of the circadian properties of time perception with antidepressant effects of chronotherapeutics and suggest the potential utility of time production in predicting clinical outcome of bipolar depression.

Original languageEnglish
Pages (from-to)72-79
Number of pages8
JournalJournal of Affective Disorders
Publication statusPublished - Feb 15 2020


  • Antidepressant chronotherapeutics
  • Bipolar disorder
  • Circadian dynamics
  • Sleep deprivation
  • Time perception

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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