Table 1.

Clinical Questions Addressed in the Review

Clinical Questions	Observations promoting questions
Risk Factors
Is age a risk factor for developing a CRSD?	Basic research suggests that the circadian system undergoes major changes over the course of the life cycle.
Is gender a risk factor for developing a CRSD?	Gender may be a significant risk factor for CRSDs, given the interaction between the circadian and reproductive systems, including the menstrual cycle. Gender could be also an important risk factor because of employment patterns or childcare duties.
Is insufficient, excessive, or inappropriately timed light exposure a risk factor for developing a CRSD?	Because sunlight is the most important circadian time cue in humans, it is logical to ask whether the intensity, duration or timing of light exposure is a risk factor for CRSDs.
Is there a familial (genetic) predisposition for developing a CRSD?	Many patients with CRSDs report family members with similar problems. Furthermore, recent advances in molecular biology have identified “clock genes” that could be involved in the pathophysiology of CRSDs.
Assessment Tools
How useful is a sleep log (diary)?	Sleep-wake diaries (sleep logs) are consistently recommended as a method for evaluating sleep schedules in CRSD patients.
How useful is actigraphy?	The ICSD-2 diagnostic criteria for most CRSDs require that abnormalities in the timing of the habitual sleep pattern be documented with either sleep logs or actigraphy for seven days or more.1
How useful is the MEQ in clinical practice?	The Morningness-Eveningness Questionnaire (MEQ) developed by Horne and Ostberg in 19767 has become a widely employed instrument to classify individuals with extreme circadian tendencies (“larks” and “owls”).
Is a PSG necessary in the clinical management of a CRSD?	Polysomnography (PSG) is considered the “gold standard” for sleep assessment. In some of the research studies we reviewed, PSG, and in a few instances, multiple sleep latency tests (MSLTs) have been employed.
When might it be useful (or necessary) to assess circadian phase and/or amplitude using a marker such as core body temperature (CBT) or melatonin?	Methods have been refined that can determine circadian phase (circadian time [CT]) in humans.
Treatment
Is prescribed sleep/wake scheduling safe and effective?	Chronotherapy was the first recognized treatment for a CRSD and can be considered an example of prescribed sleep scheduling, based on a hypothesized circadian mechanism. Another example is prescribed napping proposed as a countermeasure for night workers.
Is timed light exposure safe and effective? Is timed melatonin administration safe and effective?	Inasmuch as CRSDs involve a misalignment of the circadian system with the preferred sleep schedule, can this be corrected by circadian phase shifting?
Are sleep-promoting medications safe and effective?	Insomnia can be one of the symptoms of a CRSD. Excessive sleepiness can be one of the symptoms of CRSDs.
Are wakefulness-promoting medications safe and effective?