**1. Introduction: what every clinician needs to know**

The intrinsic circadian system synchronizes basic physiologic functions such as temperature regulation, appetite, and hormonal homeostasis and is responsible for the stable sleep and wake states that occur at regular times with respect to day and night. The term circadian derives from the Latin words "circa," meaning approximately, and "diem," meaning day, which emphasize that the intrinsic cycle is usually not exactly 24 hours in length [1]. The average circadian cycle length is generally 24.2 hours, which means that the cycle always requires entrainment to the environment because the day is exactly 24 hours long. Light is the most potent mechanism of entrainment, but meals and exercise also have an impact on entrainment [1–3]. Dysynchrony between a person's internal circadian system and their desired wake and sleep periods can lead to one of 6 different types of circadian rhythm sleep–wake disorders (CRSWDs). These disorders can present clinically with symptoms of insomnia and/or excessive daytime sleepiness, along with impairments in cognitive, emotional, and social functioning. A key feature of these conditions is that re-alignment of the intrinsic circadian period to the desired circadian period leads to resolution of symptoms.

CRSWDs may be due to a primary problem with the circadian system, such as altered sensitivity of the circadian system to light, and genetic and/or age-related factors that disrupt the intrinsic period of the system.

The diagnosis of CRSWDs can be difficult, due to the overlapping symptoms with other sleep disorders and medical conditions. Recognizing consistent patterns in abnormal sleep schedules is key to helping differentiate CRSWDs from other disorders. CRSWDs are primarily clinical diagnoses and use of a detailed sleep diary is an important part of the evaluation. Other objective measures such as actigraphy and melatonin measurements can supplement information obtained from the patient's history [4]. Polysomnography is usually not indicated unless there is a suspicion for a comorbid sleep disorder, such as a sleep-related breathing disorder.

Management of circadian rhythm sleep–wake disorders involves a combination of behavioral interventions, light therapy, and timed melatonin therapy. Treatment is individualized to the specific circadian rhythm sleep–wake disorder [5]. The goal of therapy is to gradually realign the patient's sleep and wake times with the desired schedule. The timing of light and melatonin therapies is critical to determining their biologic effects. The key biologic markers are the dim light melatonin onset (DLMO), which typically occurs approximately two hours prior to habitual sleeptime, and the core body temperature minimum (CBT-min), which typically occurs 2-3 hours prior to habitual wake up time. Exposure to light prior to the body temperature minimum will cause the circadian rhythm to delay (i.e. the next night, there will be a tendency to go to bed and wake up later). Light exposure after the core body temperature minimum will cause the circadian system to advance (i.e. the next night, there will be a tendency to go to bed and to wake up earlier). The effect of light is most potent when it is in the blue spectrum and administered close to the CBT-min. Melatonin has the opposite phase response relationship that light has; melatonin given prior to the CBT-min will cause the circadian rhythm to advance (i.e., the next night, there will be a tendency to go to bed and wake up earlier) whereas melatonin administration after the CBT-min will cause the circadian system to delay (i.e., the next night, there will be a tendency to go to bed and wake up later).

The International Classification of Sleep Disorders, third edition (ICSD-3), has the following three diagnostic criteria for all circadian rhythm sleep–wake disorders [6]:


## **2. Classification of the circadian rhythm sleep-wake disorders**

Intrinsic CRSWDs include the following: 1) advanced sleep–wake phase disorder (extreme early bird), 2) delayed sleep–wake phase disorder (extreme night owl), 3) non-24-hour sleep–wake rhythm disorder (drifting circadian rhythm), and 4) irregular sleep–wake rhythm disorder (no rhythm). The two circadian disorders caused by extrinsic factors are 1) shift work disorder and 2) jet lag disorder, both of which are due to behaviorally mediated misalignments of circadian system.
