Circadian Melatonin and Temperature Taus in Delayed Sleep-wake Phase Disorder and Non-24-hour Sleep-wake Rhythm Disorder Patients

Abstract

Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h “days” in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD ( p = 0.007, p = 0.06) and control participants ( p < 0.001, p = 0.02, respectively). Between 12% and 19% of the variance in DSWPD patients’ sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients’ persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD disorders.