It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in a society".

[3] Symptoms result when the non-entrained (free-running) endogenous circadian rhythm drifts out of alignment with the light–dark cycle in nature.

[2] The American Academy of Sleep Medicine (AASM) has provided CRSD guidelines since 2007 with the latest update released in 2015.

[2][5] People with non-24 experience daily shifts in the circadian rhythm such as peak time of alertness, body temperature minimum, metabolism and hormone secretion.

[7] Most people with this disorder find that it severely impairs their ability to function in school, in employment, and in their social lives.

Typically, they are "partially or totally unable to function in scheduled activities on a daily basis, and most cannot work at conventional jobs".

People with non-24 who force themselves to live to a normal workday "are not often successful and may develop physical and psychological complaints during waking hours, i.e. sleepiness, fatigue, headache, decreased appetite, or depressed mood.

Patients often have difficulty maintaining ordinary social lives, and some of them lose their jobs or fail to attend school.

[citation needed] Melatonin is responsible for sleep regulation, and its release is controlled by the amount of light entering the eyes.

[17] At least one case of a sighted person developing non-24 was preceded by head injury;[18] another patient diagnosed with the disorder was later found to have a "large pituitary adenoma that involved the optic chiasma".

[17] "Studies in animals suggest that a hypernyctohemeral syndrome could occur as a physiologic aftereffect of lengthening the sleep–wake cycle with chronotherapy".

[7] According to the American Academy of Sleep Medicine (AASM), "patients with free-running (FRD) rhythms are thought to reflect a failure of entrainment".

[11] A few cases have been described in which patients are subjectively blind, but are normally entrained and have an intact response to the suppressing effects of light on melatonin secretion, indicating preserved neural pathways between the retina and hypothalamus.

[28][29] The majority of people with non-24 are totally blind, and the failure of entrainment is explained by an absence of light (photic) input to reset the circadian clock.

[23] This slight deviation is, in almost everyone, corrected by exposure to environmental time cues, especially the light–dark cycle, which reset the clock and synchronize (entrain) it to the 24-hour day.

[12] The most easily observed of these is the propensity for sleep and wake; thus, people with non-24 experience symptoms of insomnia and daytime sleepiness (similar to "jet lag") when their endogenous circadian rhythms drift out of synchrony with the social/solar 24-hour day, but they conform to a conventional schedule.

Thus the overall pattern involves periodic symptoms on a weekly or monthly basis, depending on the length of the internal circadian cycle.

[2] This disorder can have symptomatic periods, where "the time of high sleep propensity gradually shifts, such that patients experience daytime hypersomnolence and nighttime insomnia".

[2] In sighted people, the diagnosis is typically made based on a history of persistently delayed sleep onset that follows a non-24-hour pattern.

Hayakawa et al. (2005) reported on the basis of 57 cases of sighted patients that the average day length was 24.9 ± 0.4 hours (with the range of 24.4–26.5).

Study authors noted that the lower rates of entrainment with tasimelteon may have been due to short duration of treatment.

The accuracy needed for successfully timing the administration of melatonin might require a period of trial and error, as does the dosage.

[medical citation needed] There are an estimated 140,000 people with non-24—both sighted and blind—in the European Union, a total prevalence of approximately 3 per 10,000, or 0.03%.

[47][48][49][50] The ability of melatonin administration to entrain free-running rhythms was first demonstrated by Redman, et al. in 1983 in rats who were maintained in a time-free environment.

[57] In 2005, ramelteon (trade name Rozerem) was the first melatonin agonist to be approved in the United States (US), indicated for insomnia treatment in adults.

[58] Melatonin in the form of prolonged release (trade name Circadin) was approved in 2007 in Europe (EU) for use as a short-term treatment, in patients 55 years and older, for primary insomnia.

Even while adhering to a typical 24-hour schedule for bedtime, rise time, work, and meals, the man's body rhythms continued to shift.