Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
Adelaide Institute for Sleep Health, School of Medicine, Flinders University, Adelaide, South Australia.
J Physiol. 2018 Dec;596(24):6249-6261. doi: 10.1113/JP275917. Epub 2018 Oct 25.
This is the first study to demonstrate an altered circadian phase shifting response in a circadian rhythm sleep disorder. Patients with delayed sleep-wake phase disorder (DSWPD) demonstrate greater sensitivity of the circadian system to the phase-delaying effects of light. Increased circadian sensitivity to light is associated with later circadian timing within both control and DSWPD groups. DSWPD patients had a greater sustained pupil response after light exposure. Treatments for DSWPD should consider sensitivity of the circadian system to light as a potential underlying vulnerability, making patients susceptible to relapse.
Patients with delayed sleep-wake phase disorder (DSWPD) exhibit delayed sleep-wake behaviour relative to desired bedtime, often leading to chronic sleep restriction and daytime dysfunction. The majority of DSWPD patients also display delayed circadian timing in the melatonin rhythm. Hypersensitivity of the circadian system to phase-delaying light is a plausible physiological basis for DSWPD vulnerability. We compared the phase shifting response to a 6.5 h light exposure (∼150 lux) between male patients with diagnosed DSWPD (n = 10; aged 20.8 ± 2.3 years) and male healthy controls (n = 11; aged 22.4 ± 3.3 years). Salivary dim light melatonin onset (DLMO) was measured under controlled conditions in dim light (<3 lux) before and after light exposure. Correcting for the circadian time of the light exposure, DSWPD patients exhibited 31.5% greater phase delay shifts than healthy controls. In both groups, a later initial melatonin phase was associated with a greater magnitude phase shift, indicating that increased circadian sensitivity to light may be a factor that contributes to delayed phase, even in non-clinical groups. DSWPD patients also had reduced pupil size following the light exposure, and showed a trend towards increased melatonin suppression during light exposure. These findings indicate that, for patients with DSWPD, assessment of light sensitivity may be an important factor that can inform behavioural therapy, including minimization of exposure to phase-delaying night-time light.
这是第一项证明睡眠-觉醒时相延迟障碍患者昼夜节律相位转移反应改变的研究。睡眠-觉醒时相延迟障碍(DSWPD)患者表现出对光的相位延迟作用的更大敏感性。昼夜节律系统对光的敏感性增加与对照组和 DSWPD 组的昼夜节律时相延迟有关。DSWPD 患者在暴露于光后瞳孔持续反应更大。DSWPD 的治疗应考虑昼夜节律系统对光的敏感性作为潜在的潜在脆弱性,使患者容易复发。
睡眠-觉醒时相延迟障碍(DSWPD)患者的睡眠-觉醒行为相对于期望的就寝时间延迟,经常导致慢性睡眠限制和白天功能障碍。大多数 DSWPD 患者的褪黑素节律也显示出昼夜节律时相延迟。昼夜节律系统对延迟光相位的超敏反应是 DSWPD 易感性的合理生理基础。我们比较了男性 DSWPD 患者(n=10;年龄 20.8±2.3 岁)和男性健康对照组(n=11;年龄 22.4±3.3 岁)在 6.5 小时光照暴露(约 150lux)下的相位转移反应。在光照暴露前和光照暴露后,在暗光(<3lux)下测量唾液褪黑素微光起始(DLMO)。校正光照的昼夜时间,DSWPD 患者的相位延迟变化比健康对照组大 31.5%。在两组中,初始褪黑素相位较晚与较大的相位转移幅度相关,表明对光的昼夜节律敏感性增加可能是导致相位延迟的一个因素,即使在非临床组中也是如此。DSWPD 患者在光照暴露后瞳孔也变小,并且在光照期间显示出增加褪黑素抑制的趋势。这些发现表明,对于 DSWPD 患者,光敏感性评估可能是一个重要因素,可以为行为治疗提供信息,包括减少对延迟相位的夜间光暴露。