Circadian tau differences and rhythm associations in delayed sleep-wake phase disorder and non-24-hour sleep-wake rhythm disorder

Introduction: Delayed Sleep-Wake Phase Disorder (DSWPD) and Non-24-hour Sleep-Wake Disorder (N24SWD) are circadian-based sleep disorders. DSWPD patients exhibit circadian rhythms that are timed approximately > 3 hours later than normal and N24SWD circadian rhythms cannot be synchronised to the 24-h light-dark cycle thus resulting in free running sleep-wake cycles that are significantly longer than the 24-h day. Greater tendency to phase delay from longer than normal period lengths and abnormal relationships between the timing of circadian rhythms and sleep/wake cycles are also hypothesised to underpin the pathology of DSWPD and N24SWD. In this study we investigated biological, sleepiness and behavioural rhythm period lengths (i.e., taus) of DSWPD, N24SWD patients and healthy control sleepers. Cross-correlation analyses were performed between different rhythm variables to examine phase angle of entrainment. The aim was to explore if behavioural rhythms, in addition to the biological circadian rhythms contribute to misalignments of sleep timing symptomatic of DSWPD and N24SWD.
Materials and methods: Twenty-six DSWPD (17m, [Mean ± Standard Deviation] age: 21.85 ± 4.97 years), 4 full-sighted N24SWD (3m, age: 25.75 ± 4.99 years) participants who met diagnostic criteria, and 18 controls (10m, age: 23.72 ± 5.10 years) participated in an 80-hour modified constant routine. A forced-desynchrony ultradian protocol of 1-hour 'days' in dim light, controlled conditions alternated 20-minute sleep opportunities with 40- minute enforced wakefulness. Subjective sleepiness ratings were recorded prior to every sleep opportunity and median reaction time (vigilance) was measured hourly. Amount of sleep obtained (sleep propensity) was derived from 20-minute sleep opportunities to quantify hourly objective sleepiness. Hourly core body temperature was recorded, and salivary melatonin assayed to measure endogenous circadian rhythms. Rhythm data were curved using the 2-component cosine model.
Results: The timing of DSWPD patients' sleeping patterns and circadian rhythm measures (i.e., core temperature, melatonin, vigilance, and subjective and objective sleepiness) were significantly delayed by 2-3 hours compared to controls. A 3 by 5 repeated measures analysis of variance was used to investigate between- and within-groups taus of core body temperature, melatonin, subjective sleepiness, sleep propensity and vigilance. There were significant main effects of both groups (F(43,4)=2.95, p=0.03, ŋ2=0.23) and different rhythms (F(43,4)=3.89, p=0.023, ŋ2=0.17) but no significant overall interaction effect. DSWPD and N24SWD patients had significantly longer melatonin and temperature taus compared to controls. There were no significant tau differences between groups as measured by subjective sleepiness, sleep propensity and vigilance rhythms. However, DSWPD patients showed a greater delay of maximum sleep propensity from minimum core body temperature. Their sleep propensity rhythms lagged behind core temperature rhythms by an hour more compared to controls' sleep propensity and core temperature rhythms.
Conclusions: Delayed circadian rhythms in DSWPD may result from larger phase angles between core body temperature and sleep propensity. This relatively delayed sleep propensity rhythm may result in later sleep timing in DSWPD patients relative to their circadian timing thus delaying their light exposure during a time that is critical to phase-advancing the circadian system.