Circadian phase and phase angle disorders in primary insomnia

Erin E. Flynn-Evans, Julia A. Shekleton, Belinda Miller, Lawrence J. Epstein, Douglas Kirsch, Lauren A. Brogna, Liza M. Burke, Erin Bremer, Jade M. Murray, Philip Gehrman, Shantha M.W. Rajaratnam, Steven W. Lockley

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia. Methods: We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days. Circadian phase was assessed from salivary dim light melatonin onset (DLMO) time during a 12-hour laboratory visit. Results: Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46 females, 35.5 ± 12.3 years [M ± SD]) and 21 controls (14 females, 34.4 ± 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 hours vs. 24:13 ± 1:30 hours, respectively; p = .84) but had a later average DLMO times (20:56 ± 1:55 hours, 18:17–01:21 vs. 22:02 ± 2:02 hours, 17:11–04:52, respectively; p = .04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 hours (± 1:43) vs. 3:10 hours (± 1:08), respectively; p = .008), of whom 10% tried to sleep at or before DLMO (compared to 0 controls), and 22% tried to sleep before or within 1 hour after DLMO (compared to 6% of controls). Conclusions: A substantial proportion (10%–22%) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.

Original languageEnglish
Article numberzsx163
Number of pages11
JournalSleep
Volume40
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • 6-sulfatoxymelatonin
  • Circadian
  • Circadian rhythms
  • DLMO
  • Insomnia
  • Melatonin
  • Phase angle

Cite this

Flynn-Evans, E. E., Shekleton, J. A., Miller, B., Epstein, L. J., Kirsch, D., Brogna, L. A., ... Lockley, S. W. (2017). Circadian phase and phase angle disorders in primary insomnia. Sleep, 40(12), [zsx163]. https://doi.org/10.1093/sleep/zsx163
Flynn-Evans, Erin E. ; Shekleton, Julia A. ; Miller, Belinda ; Epstein, Lawrence J. ; Kirsch, Douglas ; Brogna, Lauren A. ; Burke, Liza M. ; Bremer, Erin ; Murray, Jade M. ; Gehrman, Philip ; Rajaratnam, Shantha M.W. ; Lockley, Steven W. / Circadian phase and phase angle disorders in primary insomnia. In: Sleep. 2017 ; Vol. 40, No. 12.
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title = "Circadian phase and phase angle disorders in primary insomnia",
abstract = "Objectives: We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia. Methods: We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days. Circadian phase was assessed from salivary dim light melatonin onset (DLMO) time during a 12-hour laboratory visit. Results: Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46 females, 35.5 ± 12.3 years [M ± SD]) and 21 controls (14 females, 34.4 ± 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 hours vs. 24:13 ± 1:30 hours, respectively; p = .84) but had a later average DLMO times (20:56 ± 1:55 hours, 18:17–01:21 vs. 22:02 ± 2:02 hours, 17:11–04:52, respectively; p = .04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 hours (± 1:43) vs. 3:10 hours (± 1:08), respectively; p = .008), of whom 10{\%} tried to sleep at or before DLMO (compared to 0 controls), and 22{\%} tried to sleep before or within 1 hour after DLMO (compared to 6{\%} of controls). Conclusions: A substantial proportion (10{\%}–22{\%}) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.",
keywords = "6-sulfatoxymelatonin, Circadian, Circadian rhythms, DLMO, Insomnia, Melatonin, Phase angle",
author = "Flynn-Evans, {Erin E.} and Shekleton, {Julia A.} and Belinda Miller and Epstein, {Lawrence J.} and Douglas Kirsch and Brogna, {Lauren A.} and Burke, {Liza M.} and Erin Bremer and Murray, {Jade M.} and Philip Gehrman and Rajaratnam, {Shantha M.W.} and Lockley, {Steven W.}",
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Flynn-Evans, EE, Shekleton, JA, Miller, B, Epstein, LJ, Kirsch, D, Brogna, LA, Burke, LM, Bremer, E, Murray, JM, Gehrman, P, Rajaratnam, SMW & Lockley, SW 2017, 'Circadian phase and phase angle disorders in primary insomnia' Sleep, vol. 40, no. 12, zsx163. https://doi.org/10.1093/sleep/zsx163

Circadian phase and phase angle disorders in primary insomnia. / Flynn-Evans, Erin E.; Shekleton, Julia A.; Miller, Belinda; Epstein, Lawrence J.; Kirsch, Douglas; Brogna, Lauren A.; Burke, Liza M.; Bremer, Erin; Murray, Jade M.; Gehrman, Philip; Rajaratnam, Shantha M.W.; Lockley, Steven W.

In: Sleep, Vol. 40, No. 12, zsx163, 01.12.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Circadian phase and phase angle disorders in primary insomnia

AU - Flynn-Evans, Erin E.

AU - Shekleton, Julia A.

AU - Miller, Belinda

AU - Epstein, Lawrence J.

AU - Kirsch, Douglas

AU - Brogna, Lauren A.

AU - Burke, Liza M.

AU - Bremer, Erin

AU - Murray, Jade M.

AU - Gehrman, Philip

AU - Rajaratnam, Shantha M.W.

AU - Lockley, Steven W.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Objectives: We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia. Methods: We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days. Circadian phase was assessed from salivary dim light melatonin onset (DLMO) time during a 12-hour laboratory visit. Results: Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46 females, 35.5 ± 12.3 years [M ± SD]) and 21 controls (14 females, 34.4 ± 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 hours vs. 24:13 ± 1:30 hours, respectively; p = .84) but had a later average DLMO times (20:56 ± 1:55 hours, 18:17–01:21 vs. 22:02 ± 2:02 hours, 17:11–04:52, respectively; p = .04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 hours (± 1:43) vs. 3:10 hours (± 1:08), respectively; p = .008), of whom 10% tried to sleep at or before DLMO (compared to 0 controls), and 22% tried to sleep before or within 1 hour after DLMO (compared to 6% of controls). Conclusions: A substantial proportion (10%–22%) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.

AB - Objectives: We aimed to identify the prevalence of circadian phase and phase angle abnormalities in patients with insomnia. Methods: We conducted a cross-sectional, multicenter study at three sleep laboratories in the United States and Australia. Patients with insomnia and healthy control participants completed a sleep log for 7 days. Circadian phase was assessed from salivary dim light melatonin onset (DLMO) time during a 12-hour laboratory visit. Results: Seventy-nine patients meeting the Research Diagnostic Criteria for Primary, Psychophysiological, Paradoxical, and/or Idiopathic Childhood Insomnia (46 females, 35.5 ± 12.3 years [M ± SD]) and 21 controls (14 females, 34.4 ± 11.8 years). As compared to controls, patients with insomnia tried to initiate sleep on average at the same clock time (24:17 ± 1:17 hours vs. 24:13 ± 1:30 hours, respectively; p = .84) but had a later average DLMO times (20:56 ± 1:55 hours, 18:17–01:21 vs. 22:02 ± 2:02 hours, 17:11–04:52, respectively; p = .04). Consequently, patients with insomnia slept at an earlier circadian phase than controls (phase angle, bedtime-DLMO 2:13 hours (± 1:43) vs. 3:10 hours (± 1:08), respectively; p = .008), of whom 10% tried to sleep at or before DLMO (compared to 0 controls), and 22% tried to sleep before or within 1 hour after DLMO (compared to 6% of controls). Conclusions: A substantial proportion (10%–22%) of patients with insomnia initiate sleep at too early a circadian phase, implicating a circadian etiology for their insomnia. Outpatient circadian phase assessments should be considered to improve differential diagnoses in insomnia and to inform the development of appropriately timed circadian-based treatments.

KW - 6-sulfatoxymelatonin

KW - Circadian

KW - Circadian rhythms

KW - DLMO

KW - Insomnia

KW - Melatonin

KW - Phase angle

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Flynn-Evans EE, Shekleton JA, Miller B, Epstein LJ, Kirsch D, Brogna LA et al. Circadian phase and phase angle disorders in primary insomnia. Sleep. 2017 Dec 1;40(12). zsx163. https://doi.org/10.1093/sleep/zsx163