Diagnosis, Cause, and Treatment Approaches for Delayed Sleep-Wake Phase Disorder.

Delayed sleep-wake phase disorder (DSWPD) is commonly defined as an inability to fall asleep and wake at societal times resulting in excessive daytime sleepiness. Although the cause is multifaceted, delays in sleep time are largely driven by misalignment between the circadian pacemaker and the desired sleep-wake timing schedule. Current treatment approaches focus on correcting the circadian delay; however, there is a lack of data investigating combined therapies for treatment of DSWPD.

Melatonin administration alters nicotine preference consumption via signaling through high-affinity melatonin receptors.

RATIONALE: While it is known that tobacco use varies across the 24-h day, the time-of-day effects are poorly understood. Findings from several previous studies indicate a potential role for melatonin in these time-of-day effects; however, the specific underlying mechanisms have not been well characterized. Understanding of these mechanisms may lead to potential novel smoking cessation treatments. OBJECTIVE: The objective of this study is examine the role of melatonin and melatonin receptors in nicotine free-choice consumption METHODS: A two-bottle oral nicotine choice paradigm was utilized with melatonin supplementation in melatonin-deficient mice (C57BL/6J) or without melatonin supplementation in mice proficient at melatonin synthesis (C3H/Ibg) compared to melatonin-proficient mice lacking both or one of the high-affinity melatonin receptors (MT1 and MT2; double-null mutant DM, or MT1 or MT2). Preference for bitter and sweet tastants also was assessed in wild-type and MT1 and MT2 DM mice. Finally, home cage locomotor monitoring was performed to determine the effect of melatonin administration on activity patterns. RESULTS: Supplemental melatonin in drinking water significantly reduced free-choice nicotine consumption in C57BL/6J mice, which do not produce endogenous melatonin, while not altering activity patterns. Independently, genetic deletion of both MT1 and MT2 receptors in a melatonin-proficient mouse strain (C3H) resulted in significantly more nicotine consumption than controls. However, single genetic deletion of either the MT1 or MT2 receptor alone did not result in increased nicotine consumption. Deletion of MT1 and MT2 did not impact taste preference. CONCLUSIONS: This study demonstrates that nicotine consumption can be affected by exogenous or endogenous melatonin and requires at least one of the high-affinity melatonin receptors. The fact that expression of either the MT1 or MT2 melatonin receptor is sufficient to maintain lower nicotine consumption suggests functional overlap and potential mechanistic explanations.

Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review.

OBJECTIVE: This the second of two articles reviewing the scientific literature on the evaluation and treatment of circadian rhythm sleep disorders (CRSDs), employing the methodology of evidence-based medicine. We herein report on the accumulated evidence regarding the evaluation and treatment of Advamced Sleep Phase Disorder (ASPD), Delayed Sleep Phase Disorder (DSPD), Free-Running Disorder (FRD) and Irregular Sleep-Wake Rhythm ISWR). METHODS: A set of specific questions relevant to clinical practice were formulated, a systematic literature search was performed, and relevant articles were abstracted and graded. RESULTS: A substantial body of literature has accumulated that provides a rational basis the evaluation and treatment of CRSDs. Physiological assessment has involved determination of circadian phase using core body temperature and the timing of melatonin secretion. Behavioral assessment has involved sleep logs, actigraphy and the Morningness-Eveningness Questionnaire (MEQ). Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications. CONCLUSION: Circadian rhythm science has also pointed the way to rational interventions for CRSDs and these treatments have been introduced into the practice of sleep medicine with varying degrees of success. More translational research is needed using subjects who meet current diagnostic criteria.

Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Academy of Sleep Medicine review.

OBJECTIVE: This the first of two articles reviewing the scientific literature on the evaluation and treatment of circadian rhythm sleep disorders (CRSDs), employing the methodology of evidence-based medicine. In this first part of this paper, the general principles of circadian biology that underlie clinical evaluation and treatment are reviewed. We then report on the accumulated evidence regarding the evaluation and treatment of shift work disorder (SWD) and jet lag disorder (JLD). METHODS: A set of specific questions relevant to clinical practice were formulated, a systematic literature search was performed, and relevant articles were abstracted and graded. RESULTS: A substantial body of literature has accumulated that provides a rational basis the evaluation and treatment of SWD and JLD. Physiological assessment has involved determination of circadian phase using core body temperature and the timing of melatonin secretion. Behavioral assessment has involved sleep logs, actigraphy and the Morningness-Eveningness Questionnaire (MEQ). Treatment interventions fall into three broad categories: 1) prescribed sleep scheduling, 2) circadian phase shifting ("resetting the clock"), and 3) symptomatic treatment using hypnotic and stimulant medications. CONCLUSION: Circadian rhythm science has also pointed the way to rational interventions for the SWD and JLD, and these treatments have been introduced into the practice of sleep medicine with varying degrees of success. More translational research is needed using subjects who meet current diagnostic criteria.