Running on Empty: Of Hypopinealism and Human Seasonality

The pineal hormone melatonin is the natural transducer of the environmental light-dark signal to the body. Although the responsiveness to photoperiod is well-conserved in humans, only about 25 percent of the human population experiences seasonal changes in behavior. As a consequence, humans seem to have adapted-at least partly-to the seasonal changes in day length. The aim of the study was to demonstrate that the individual melatonin deficit marker DOC (degree of pineal calcification) is related to variation of seasonal phenomena in humans. Out of 3,011 patients in which cranial computer tomography (cCT) was performed for diagnostic reasons, 97 consecutive "healthy" subjects (43 female, 54 male; age 18-68 yrs, mean ± SD: 35.0 ± 13.1) were included. Exclusion criteria were pathological finding in cCT, acute/chronic illness including alcohol/drug abuse, shift work, and medication, which are known to influence melatonin excretion. The degree of pineal calcification (DOC) was semiquantitatively determined using the previously validated method. The Seasonal Pattern Assessment Questionnaire (SPAQ) was performed in a telephone interview. Twenty-six subjects fulfilled the criteria for seasonal affective disorder (SAD) or subsyndromal (S) SAD. Seasonality was more pronounced in women than in men (SPAQ seasonality score: 7.8 ± 4.0 vs. 4.9 ± 4.5; p = 0.001) and negatively and significantly associated with age (r = -0.178; p = 0.04). The subjective sleep length significantly varied between seasons (one-way repeated measures ANOVA: F = 45.75; p < 0.0001), with sleep during winter being 53 min (± 70 min) longer than during summer. Controlling for age, the total seasonality score was negatively and significantly associated with DOC (r(94) = -0.214; p = 0.036). Data confirm earlier studies with respect to distribution of seasonality with sex and age. The survival of seasonality in the sleep length of people living in an urban environment underlines functionality of the circadian timing system in modern societies. Moreover, data confirm for the first time that diminished experience of seasonality in behavior is associated with a reduced individual capacity to produce melatonin

Night-time activity forecast by season and weather in a longitudinal design:natural light effects on three years' rest-activity cycles in nursing home residents with dementia

Backround: Night-time agitation is a frequent symptom of dementia. It often causes nursing home admission and has been linked to circadian rhythm disturbances. A positive influence of light interventions on night-time agitation was shown in several studies. The aim of our study was to investigate whether there is a long-term association between regional weather data (as indicator for daylight availability) and 24-hour variations of motor activity. Methods: Motor activity of 20 elderly nursing home residents living with dementia was analyzed using recordings of continuously worn wrist activity monitors over a three-year period. The average recording duration was 479 206 days per participant (mean SD). Regional cloud amount and day length data from the local weather station (latitude: 52 degrees 56N) were included in the analysis to investigate their effects on several activity variables. Results: Nocturnal rest, here defined as the five consecutive hours with the least motor activity during 24 hours (L5), was the most predictable activity variable per participant. There was a significant interaction of night-time activity with day length and cloud amount (F-1,F-1174 = 4.39; p = 0.036). Night-time activity was higher on cloudy short days than on clear short days (p = 0.007), and it was also higher on cloudy short days than on cloudy long days (p = 0.032). Conclusions: The need for sufficient zeitgeber (time cue) strength during winter time, especially when days are short and skies are cloudy, is crucial for elderly people living with dementia. Activity forecast by season and weather might be a valuable approach to anticipate adequately complementary use of electrical light and thereby foster lower night-time activity

The alerting effect of the wake maintenance zone during 40 hours of sleep deprivation

Under entrained conditions, the accumulation of homeostatic sleep pressure in the evening is opposed by a strong circadian arousal signal prior to the dim light melatonin onset, called the Wake Maintenance Zone (WMZ). This study aimed at investigating the impact of the WMZ on different cognitive performance tests, as well as on subjective and objective sleepiness. Twelve young male participants completed a constant routine protocol with 40 h of extended wakefulness that included two WMZs. Cognitive tests and saliva samples were assessed hourly, while the electroencephalogram (EEG) was recorded continuously. Participants improved in cognitive response inhibition during WMZ1 (13.5 h awake) and sustained attention during WMZ2 (37.5 h awake), but not in higher executive function tests. There were significant EEG power density reductions in the delta/theta frequency range during WMZ1 and in delta/theta, alpha, and sigma/beta ranges during WMZ2, with a greater change in the sigma/beta range during WMZ2 compared toWMZ1. EEG power reductions coincided during WMZ1 with stable subjective sleepiness and sustained attention. During WMZ2, EEG power reductions were more pronounced and coincided with improved sustained attention. Our results suggest the circadian arousal signal in the evening differently modulates cognitive functions and EEG power depending on the duration of prior wakefulness

Impact of melatonin and light on parameters of the circadian system

Einleitung: Die vorliegende kumulative Promotionsschrift beinhaltet Ergebnisse aus drei Studien. Dabei wird den Fragen nachgegangen, 1) wie das circadiane System endogen durch Melatonin und exogen durch Licht und Melatonin beeinflusst wird und 2) wie man diese Einflüsse klinisch nutzen kann, um Störungen des circadianen Systems und den daraus folgenden Symptomen vorzubeugen oder diese zu lindern. Circadiane Rhythmen von Physiologie und Verhalten werden über Licht und Dunkelheit mit dem äußeren 24-Stunden Tag synchronisiert. Das Hormon Melatonin spielt dabei eine vermittelnde Rolle. Defizite in der nächtlichen Melatonin-Sekretion könnten somit an einer gestörten circadianen Steuerung beteiligt sein und klinische Symptome hervorrufen. Methoden: In Studie#1 wurden in einem doppelblinden, Placebo- kontrollierten, cross-over Studiendesign 14 Patienten mit neurologisch- psychiatrischen schlafbezogenen Störungen mit täglich 3mg exogenem Melatonin über vier Wochen behandelt. Einschlusskriterium war quantitativ reduzierter Rapid-Eye-Movement (REM) Schlaf. Studie#2 beinhaltet die Analyse der Melatonin-Konzentrations-Profile im Urin von 75 gesunden Probanden zwischen 20 und 84 Jahren. In Studie#3 wurde bei 9 gesunden Probanden der Einfluss von abendlicher, 30 Minuten dauernder Beleuchtung mit verschiedenen Alltags-Lampen auf die Melatonin-Ausschüttung und das subjektive Befinden untersucht. Ergebnisse: (#1) Das exogene Melatonin erhöhte den REM-Schlafanteil, verstärkte die physiologische Körpertemperaturabnahme während der Nacht, und verbesserte die REM-Schlaf- Kontinuität. Gleichzeitig verbesserten sich der Clinical-Global-Impression-Scale und die Subskala „daytime-dysfunction“ im Pittsburgh-Sleep-Quality-Index im Vergleich zur Placebo-Bedingung bei den Patienten, welche Placebo vor Melatonin erhielten. Wenn die Placebo-Bedingung nach der Melatonin-Bedingung stattfand, überdauerten die positiven Effekte die Melatonin-Einnahme sogar um vier Wochen. (#2) Es zeigte sich eine bis zu 20-fache Variabilität in der Sekretion des endogenen Melatonins und eine signifikante Altersabhängigkeit: die Menge des ausgeschütteten Melatonins nahm mit zunehmendem Alter ab. (#3) Alle abendlichen Beleuchtungssituationen mit Blauanteil reduzierten den normalen Anstieg der Melatonin-Sekretion im Gegensatz zur Kontrollbedingung und zu einer Beleuchtung ohne Blauanteil; drei von den Beleuchtungssituationen mit Blauanteil steigerten auch signifikant die subjektive Wachheit. Schlussfolgerung: Die Ergebnisse der drei Studien zeigen zusammengefasst, dass (#1) exogenes Melatonin in der Lage ist, den bei Schlafstörungen manifestierten Störungen der circadianen Steuerung entgegenzuwirken; (#2) die Melatonin-Sekretion mit dem Alter abnimmt, aber aufgrund der hohen interindividuellen Variabilität kein geeigneter Indikator eines Melatonin-Defizits ist; und (#3) der abendliche Anstieg der Melatonin- Produktion durch allgemein gebräuchliche Beleuchtung unterdrückt wird, und diese Unterdrückung durch Gebrauch von Lampen ohne Blauanteil verhindert werden kann.Introduction: This cumulative thesis comprises results of three studies. It pursues the questions of 1) how the circadian system is influenced endogenously by melatonin and exogenously by light and melatonin; and 2) how these influences can be used in clinical treatment to prevent or mitigate disturbances of the circadian system and resulting symptoms. Light and darkness synchronize physiological and behavioral circadian rhythms with the external diurnal rhythm. The hormone melatonin acts as a mediator. Irregularities in the nocturnal melatonin secretion can thus contribute to an impaired circadian regulation and cause clinical symptoms. Methodology: In study#1, 14patients suffering from neurological-psychiatric sleep disorders were treated with daily doses of 3mg exogenous melatonin over a period of four weeks in a double-blind, placebo-controlled, cross-over design. The inclusion criterion was a reduced quantity of rapid eye movement (REM) sleep. Study#2 analyses the melatonin concentration profiles in urine of 75healthy volunteers between the ages of 20and84. In study#3, 9healthy volunteers were exposed to light from various conventional lamps for 30minutes during the evening to determine the influence of the light on melatonin secretion and subjective feelings. Results: (#1) Exogenous melatonin increased the proportion of REMsleep, the physiological decline in body temperature during the night, and improved REMsleep continuity. Subjects who were given the placebo prior to the melatonin also showed improved ratings on the Clinical-Global-Impression-Scale and on the subscale “daytime-dysfunction” in the Pittsburgh-Sleep- Quality- Index compared to placebo conditions. If the placebo condition followed the melatonin condition, the beneficial effects even outlasted the melatonin intake by four weeks. Study#2 showed an up to twenty-fold variability in endogenous melatonin secretion as well as a significant age dependency: the amount of melatonin secreted decreases with increasing age. (#3) Evening exposure to all lighting conditions involving blue portions reduced the normal increase in melatonin secretion in contrast to both the control condition and the exposure to light without blue portion; three of the lighting conditions involving blue portions increased subjective alertness. Conclusion: The results of the three studies show that (#1) exogenous melatonin can counter the disturbances in the circadian regulation manifest in sleep disorders; (#2) though melatonin secretion decreases with increasing age, its variation between individual subjects is so high that it is inapplicable as an indicator of a melatonin deficit; and (#3) common lighting in the evening inhibits the increase of melatonin production while the use of lamps without blue light can prevent such an inhibition

Out of the Lab and into the Bathroom: Evening Short-Term Exposure to Conventional Light Suppresses Melatonin and Increases Alertness Perception

Life in 24-h society relies on the use of artificial light at night that might disrupt synchronization of the endogenous circadian timing system to the solar day. This could have a negative impact on sleep–wake patterns and psychiatric symptoms. The aim of the study was to investigate the influence of evening light emitted by domestic and work place lamps in a naturalistic setting on melatonin levels and alertness in humans. Healthy subjects (6 male, 3 female, 22–33 years) were exposed to constant dim light (&amp;lt;10 lx) for six evenings from 7:00 p.m. to midnight. On evenings 2 through 6, 1 h before habitual bedtime, they were also exposed to light emitted by 5 different conventional lamps for 30 min. Exposure to yellow light did not alter the increase of melatonin in saliva compared to dim light baseline during (38 ± 27 pg/mL vs. 39 ± 23 pg/mL) and after light exposure (39 ± 22 pg/mL vs. 44 ± 26 pg/mL). In contrast, lighting conditions including blue components reduced melatonin increase significantly both during (office daylight white: 25 ± 16 pg/mL, bathroom daylight white: 24 ± 10 pg/mL, Planon warm white: 26 ± 14 pg/mL, hall daylight white: 22 ± 14 pg/mL) and after light exposure (office daylight white: 25 ± 15 pg/mL, bathroom daylight white: 23 ± 9 pg/mL, Planon warm white: 24 ± 13 pg/mL, hall daylight white: 22 ± 26 pg/mL). Subjective alertness was significantly increased after exposure to three of the lighting conditions which included blue spectral components in their spectra. Evening exposure to conventional lamps in an everyday setting influences melatonin excretion and alertness perception within 30 min