Micic Gorica, Lovato Nicole, Gradisar Michael, Burgess Helen J, Ferguson Sally A, Lack Leon
Flinders University of South Australia, Adelaide, SA, Australia
Flinders University of South Australia, Adelaide, SA, Australia Adelaide Institute for Sleep Health: A Flinders Centre of Research Excellence, School of Medicine, Faculty of Medicine, Nursing and Health Sciences, Flinders University, Bedford Park, South Australia, Australia.
J Biol Rhythms. 2016 Aug;31(4):387-405. doi: 10.1177/0748730416650069. Epub 2016 Jun 16.
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.
我们的目标是研究与正常昼夜节律同步的个体相比，睡眠-清醒时相延迟障碍患者（DSWPD）和非24小时睡眠-清醒节律障碍患者（N24SWD）的内源性核心体温节律和褪黑素节律的周期长度（即τ值）。在一个80小时的超日节律改良持续程序中测量昼夜节律，该程序由80个超短的1小时“白天”组成，参与者有20分钟的睡眠机会，与40分钟的强制清醒交替。我们招募了一个基于社区的样本，其中包括26名符合诊断标准的DSWPD患者（17名男性，9名女性；年龄，21.85±4.97岁）和18名健康对照者（10名男性，8名女性；年龄，23.72±5.10岁）。此外，4名视力正常的患者（3名男性，1名女性；年龄，25.75±4.99岁）被诊断为N24SWD，并作为一个独立的研究组纳入。使用可摄入的核心体温胶囊记录每分钟的温度，将其平均以获得80个每小时的数据点。每半小时评估一次唾液褪黑素浓度，以确定在80小时程序开始和结束时暗光褪黑素开始的时间。DSWPD患者的褪黑素节律τ值（24小时34分钟±17分钟）明显长于对照组（24小时22分钟±15分钟，p = 0.03，d = 0.70）。DSWPD患者的体温节律τ值（24小时34分钟±26分钟）相对于对照组（24小时13分钟±15分钟，p = 0.01，d = 0.80）更长，这进一步支持了这些结果。N24SWD患者的褪黑素（25小时±19分钟）和体温（24小时52分钟±17分钟）τ值比DSWPD患者（p = 0.007，p = 0.06）和对照组参与者（分别为p < 0.001，p = 0.02）都更长。DSWPD患者睡眠时间变化的12%至19%可由更长的τ值来解释。这表明昼夜节律更长的τ值可能导致DSWPD患者持续的延迟倾向、频繁的治疗无反应以及治疗后的复发。此外，其他因素也可能导致DSWPD和N24SWD障碍中的失调。
