The dim light melatonin onset across ages, methodologies, and sex and its relationship with morningness/eveningness

Abstract The onset of melatonin secretion, the dim light melatonin onset (DLMO), is a tool for determining the phase of the circadian timing system. Although small studies have investigated the impacts of age and methods of calculating DLMO, there is no DLMO reference range. In the current study, the saliva DLMO from 3579 participants from 121 published studies and plasma DLMO from 818 healthy controls from 31 studies (aged 3–73 years) were analyzed. In a subset of 53 papers (1749 participants), individual saliva DLMO and Morningness Eveningness Questionaire (MEQ) scores were obtained from authors or mined from publications and a reference range was constructed. Saliva DLMO was earliest in children to 10 years of age and latest around 20 years of age and thereafter advanced with age by 30 min in the oldest participants. Melatonin assay methods and DLMO calculation methods had little effect on the determination of the DLMO. Saliva DLMO was correlated (p < 0.001) with the MEQ score; lower MEQ scores were associated with later DLMO. MEQ scores increased with age, reflecting a tendency toward morningness. An evaluation of 14 saliva DLMO studies of clinically diagnosed patients living with delayed sleep–wake phase disorder (mean ages 20 to 31 years) revealed mean saliva DLMO within the reference range albeit at the late extreme. Peak plasma melatonin levels from 179 studies of healthy participants revealed a high degree of variability within studies and age groups, but only a small decline between the 20 and 50 years and lowest levels after 70 years.

Circadian phase and its relationship to nighttime sleep in toddlers. J Biol Rhythms. 2013;28:322-31.                       The source and type of data obtained in the data sets made available by researchers or mined from the literature.

Reference Individual provider of the data and their institution
Source DLMO Age MEQ [1] Stephanie J. Crowley The saliva DLMO (mean ± SD) for subjects clinically diagnosed with DSWPD or similar and their mean ages. Also plotted are the n-weighted saliva DLMO for healthy subjects ().
The reference range for healthy individuals is shown as the shaded area.
The papers used to create the figure above and a brief description of the criteria used for the diagnosis of DSWPD.

Reference
Criteria for diagnosis of DSPS [1] Patients met the ICSD-3 criteria A-E for DSWPD. [2] Participants reported at least a 2-hour difference between desired and habitual bedtime, subjective sleep latency at the desired bedtime that suggested sleep onset did not occur until the habitual bedtime.
Subjects had a habitual bedtime later than midnight with a complaint of a difficulty adapting their sleep timing to standard work/school schedules. [4] Habitual Bedtime varied from 00:30 to 04:00 hours (01:36 ± 1:14 hours). [5] Diagnostic criteria of the ICSD ; (1) problems falling asleep in the evening, (2) falling asleep after 2 am at least three days a week, (3) ability to sleep until early afternoon, (4) problems waking up in time for school/ studies, (5) early wake-up times associated with extreme daytime sleepiness. [6] Had evening-type MEQ, a minimum of 2-h discrepancy between their preferred and current sleep pattern, sleep onset later than 1:00 am but sound sleep quality [7] DSWPD patients were eligible if their DLMO time was later than 23.00 h and classified as having 'circadian DSWPD' with DLMO within 30 min before desired bedtime or after desired bedtime. [8] Met the ICSD diagnostic criteria for DSPS including complaints of sleep onset insomnia and phase delay of the major sleep episode using two-week sleep diaries. All had subjective complaints of an inability to initiate sleep at a desired clock time which was earlier than their markedly delayed habitual sleep times. [9] Met the ICSD criteria for DSWPD as determined by a sleep physician. Controls had a sleep onset no later than 12:30 am, an intermediate MEQ score (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)).
[10] Participants met diagnostic criteria for DSPD based on clinical interview by a sleep physician. Participants were classified into phenotype groups based on the relationship between DLMO and desired bedtime (DBT). A circadian DSPD phenotype was defined as having a DLMO time at or after DBT. [11] Idiopathic chronic SOI, defined as a sleep onset later than 20:30 hours for children at age 6 years, and for older children 15 min later per year. [12] Subjects met ICSD criteria for DSPS. Reported a delay in sleep and wake times relative to the demands of society and an inability to fall asleep at conventional or desired times, as well as difficulty awakening in the morning. [13] DSPD subjects had (a) sleep onset later than 01:00 a.m. (b) late sleep offset and great difficulties rising in the morning; (c) if allowed to choose their own sleep-wake rhythm, they exhibited improved sleep quality and duration for age. [14] Presence of a misalignment between the participant's usual sleep-wake times and routine schedule, prospectively defined as an obligatory morning commitment requiring waking 1-2.5 h earlier than average wake time at least 1 day per week. [15] Diagnostic criteria of the ICSD ; (1) problems falling asleep in the evening, (2) falling asleep after 2 am at least three days a week, (3) ability to sleep until early afternoon, (4) problems waking up in time for school/ studies, (5) early wake-up times associated with extreme daytime sleepiness. [16] Idiopathic chronic SOI, defined as a sleep onset later than 20:30 hours for children at age 6 years, and for older children 15 min later per year. [17] Diagnosis of DSPD according to the standard criteria of the International Classification of Sleep Disorders, second edition (ICSD-2 and a clinical interview conducted by a psychiatrist-sleep specialist. [18] Diagnosed with DSWPD according to the ICSD criteria [19] Patients met ICSD criteria [20] Patients completed an online questionnaire assessing the time of falling asleep, trouble waking up in the morning, sleep maintenance problems, restless legs, snoring, apnoea and daytime sleepiness. Patients falling asleep late or having trouble waking up at a conventional time in the morning were studied. The peak plasma melatonin levels in healthy subjects at different ages from 18 papers, where both young and older subjects were studied simultaneously. The median rate of change in melatonin levels was determined and studies divided into those changing at rates above (red lines) and below the median (black lines). Note that the weighted mean levels of the "young" fast declining group was higher than the slowly declining group, but means were similar in the older groups.
The following "Peak excretion of the main melatonin metabolite 6-sulphatoxymelatonin during the night was lower than normal and/or delayed in comparison with non-insomniac elderly people."