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.

The pupillary light reflex distinguishes between circadian and non-circadian delayed sleep phase disorder (DSPD) phenotypes in young adults

“…DSPD patients are often miscategorised as insomnia patients, due to seemingly similar presentations when adequate sleep opportunity at the desired sleep time is not present [ 1 , 3 ]. A recent study reported that up to 22% of insomnia patients have abnormal circadian timing relative to the sleep-wake cycle, suggesting a circadian mechanism for their sleep disturbances [ 25 ]. Further, the two phenotypes of DSPD receive the same clinical diagnosis based on behavioural symptomology, despite exhibiting distinct physiology (i.e., differences in circadian timing).…”

Imaging Individual Differences in the Response of the Human Suprachiasmatic Area to Light

“…Circadian dysfunction has been associated with several chronic disease states, including mood disorders ( 10 , 28 ), metabolic and cardiovascular disease ( 29 ) and sleep disorders ( 11 , 14 , 30 ). Abnormalities in circadian light sensitivity may be a trait vulnerability for mood disorders with variable or decreased sensitivity being observed in seasonal affective disorder ( 12 ), while hypersensitivity to light has been observed in bipolar disorder ( 10 , 28 ), and in some sleep disorders or disturbances ( 11 , 31 ).…”

What time is it? A tale of three clocks, with implications for personalized medicine

“…Even among individuals living in the same social time zone and maintaining the same sleep‐wake rest‐activity schedules, there are wide ranges in circadian time (~5 hours in healthy young individuals, 2 ~8 hours in people with insomnia, 3 and even more dramatic differences in patient populations, including patients with circadian rhythm sleep disorders (eg, some individuals with delayed sleep phase syndrome 4 and free‐running or abnormally entrained blind individuals 5 ). There may be several reasons for this wide range in circadian time relative to social time, including individual differences in behavior (eg, self‐selected light exposure patterns from both natural [including different seasons] and artificial sources 6,7 ) and genetic factors 8 related to sleep and circadian regulation.…”