The Effects of a Blue Monochromatic Light Intervention on Evening-type Individuals' Sleep and Circadian Rhythms

The present project is aimed to contribute with new knowledge concerning how light conditions in the physical environment can be manipulated to alter the sleep and circadian rhythms of individuals with an evening-type circadian rhythm. More precisely, the study will explore whether exposure to blue light (compared to a full spectrum light control condition) during the morning hours advance the circadian rhythms of evening-type individuals, towards that which is more similar to the daily rhythm of morning-type individuals. This study is important as it has been found that evening-type adolescents and adults are at higher risk of poor academic performance and demonstrate lower intellectual performance when tested at their nonoptimal early times of day, and given the fact that most schools and workplaces structure their working hours during such early hours of the day. Such an intervention could thus help evening-type individuals better adjust to the different early day requirements that they are exposed to. The project involves a three-day intervention where participants will be exposed to blue monochromatic light, administered through ceiling mounted light emitting diode (LED)-based room lighting, in the early hours of each morning for a duration of 60 min. The participants' sleep, circadian rhythm and waking function will be assessed both objectively and subjectively. The effects of the intervention are transferable to real life educational and work settings and can thus be applied in naturalistic settings. The intervention is based on the new laboratory infrastructure available at the sleep laboratory situated in Christies gate 12.

Background:

Morningness/eveningness is a phenomenon that reflects the tendency to be an "early morning bird" or a "late night owl" and is thus a source of inter-individual variation in timing of sleep and other behaviors. Evening- and morning-type individuals demonstrate differences that derive internally regarding the circadian phase of their endogenous biological clock. A certain group of individuals referred to as morning-type individuals have been consistently found to perform better in the morning, whereas evening-type individuals appear to be more alert and perform better in the evening. Morning-type individuals have earlier bed- and rise times than evening-types, while evening-type individuals have been known to report significantly later bed- and rise-times compared to morning-type individuals. In addition, evening-type adolescents have been known to demonstrate poorer academic and intellectual performances during their nonpreferred, i.e., early hours of the day.

Circadian rhythms are known as biological processes that display endogenous, entrainable oscillations in a period of about 24 hours. These rhythms have been found to be controlled by the circadian pacemaker, which is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. These 24-hour rhythms manifest themselves in an observable manner within numerous physiological measures, such as the sleep-wake cycle, the core body temperature, and the excretion of hormones such as melatonin. The core body temperature falls during the night and reaches its lowest point (nadir) in the early morning, after which it starts to rise again. Melatonin secretion follows a curve which is almost inverse compared to the core body temperature rhythm, and is sensitive to light exposure which inhibits melatonin secretion. Melatonin either in plasma, saliva or urine is regarded as an objective marker of circadian rhythms, of which the dim light melatonin onset (time when melatonin reaches 4 pg/ml in saliva) is the most commonly used parameter.

Sleep is known to be most easily initiated when the core body temperature is falling and as the melatonin level is rising. It is also known to be most easily initiated in a timeframe of six hours before nadir until a couple of hours after nadir of the core body temperature.

Evening-type individuals experience increased sleepiness and poorer performances during the early hours of the morning, as there is a mismatch between their circadian rhythms and their requirement of being awake at such early hours. Sleepiness is known to have severe implications for performance.

However, as mentioned, the SCN outputs are entrainable and light is the strongest time-giver for individuals' circadian pacemakers. Thus, the timing of light exposure has the potential to either phase advance or phase delay one's circadian rhythm. Exposure to light in the hours before nadir, during the evening, will lead to individuals delaying their circadian rhythm. On the other side, exposure to light in the hours after nadir, during the morning hours, has the potential to phase advance individuals' circadian rhythms. Light can shift the circadian phase, but this effect is dependent on the timing of light, duration of light exposure, and the intensity of light where higher intensities have been demonstrated to be associated with greater effects. Another property of light concerns the wavelengths that it emits, where blue light has been shown to produce significantly stronger phase shifting effects than lights of other wavelengths of the visible spectrum. The effects of blue-light on the circadian system has been attributed to a photoresponsive cell population in the retina that contains the photopigment melanopsin, which is highly sensitive to blue light. These cells send signals directly to the SCN, and also form connections to areas associated with wakefulness such as the striatum and the brain stem. The sensitivity to melanopsin has been demonstrated to be highest in a blue light range around 460 nm.

To the best of our knowledge, no study has been conducted to test the effects of a blue monochromatic light intervention administered via standard room lightning on phase advancement of the circadian rhythms of evening-type individuals. Consequently, our aim is to assess whether blue light as compared to standard white light, administered via standard room lightning, can alter the sleep and circadian rhythm of evening-type individuals, causing a phase advance.

Hypothesis:

Three consecutive mornings of one hour exposure to monochromatic light (40 lx, irradiance = 88,79 µW/cm2) with peak wavelength of 455 nm (blue light) will, compared to full spectrum light (2500 Kelvin) with equal photon flux as the blue light: a) lead to a phase advance of the circadian rhythm of evening-type individuals; b) increase waking function assessed with subjective and objective measures in the morning; and c) decrease participants self-reported sleepiness in the morning, d) reduce sleep onset latency and e) advance sleep onset time.

We will adjust the light intensity to make sure that the photon energy is the same across the two conditions.

Methods

Sample and procedure:

Our aim is to recruit a sample of minimum 34 participants from the University of Bergen. Inclusion criteria is scoring below 42 on the Horne-Östberg Morningness-Eveningness Questionnaire, as this categorizes moderate and definitely evening types. Participants will be excluded if a positive case is indicated on the Mood Disorder Questionnaire (MDQ), indicating the presence or history of bipolar disorder. Participants will also be excluded if they have worked night shifts during the past three months. The participants will be exposed to the blue light intervention in a randomized, blinded, controlled study. The participants will be assessed with subjective and objective measures of sleep for 3 days (Tuesday - Thursday) a week before the three-day blue light intervention. They will also be assessed with the same subjective and objective measures during the three-day intervention period. More precisely, sleep will be assessed by actigraphy and sleep diary. One day before the intervention and one day after the intervention, circadian rhythm will be measured by saliva samples for estimation of dim light melatonin onset. Flexibility will also be measured before intervention through the Circadian Type Inventory. Waking function will be assessed on the days the intervention is given with the Karolinska Sleepiness Scale and Psychomotor Vigilance Task.

Instruments/measures:

Circadian Type Inventory: an instrument with two factors. Individuals scoring high on the first dimension (Flexible/Rigid) are more flexible in their ability to stay awake at odd times of day or night. Those who score high on the second factor (Languid/Vigorous) tend to report difficulty in overcoming drowsiness, especially in the morning. CTI will be distributed to participants before the light intervention.

Munich ChronoType Questionnaire: a useful tool for determining chronotype based on sleep behaviors, such as bed- and rise-times, clock time when one becomes fully awake, in addition to some other points (e.g., sleep latency). MCTQ will be distributed to participants before the light intervention.

The Horne-Östberg Morningness-Eveningness Questionnaire (MEQ): a test that has been widely used to assess morningness-eveningness. MEQ will be distributed to participants for screening purposes.

Mood Disorder Questionnaire (MDQ): MDQ is a validated self-report instrument that screens for the presence of a lifetime history of bipolar disorder. It contains 13 yes/no items that cover topics such as mood, self-confidence, energy, sociability, interest in sex, loquaciousness, distractibility, and other behaviors. There are in addition two questions assessing whether the symptoms ever co-occurred and to which degree the symptoms caused functional impairment. A positive case entails endorsement of 7 or more of the 13 symptoms, endorsement of the co-occurrence item and reporting moderate or serious degree of functional impairment. The MDQ will only be administered for screening purposes at baseline.

Actigraphy: Wrist-worn accelerometers and clocks to be worn during the same period as the sleep diary. Data can be converted to objective sleep parameters. This watch will be worn the week before intervention for three days, on the night before Wednesday, Thursday and Friday. It will also be worn in the intervention week on the three intervention days, on the night before Wednesday, Thursday and Friday.

Sleep diary: Daily subjective estimates of bedtime, rise-time, sleep latency, number of awakenings, wake time after sleep onset, final awakening time, rise time, total sleep time, sleep efficiency, sleep quality and daytime functioning.

The questionnaire will be distributed to the participants the week before intervention for three days, on the night before Wednesday, Thursday and Friday. It will also be given in the intervention week on the three intervention days, on the night before Wednesday, Thursday and Friday. Two of the questions are filled before the participants go to bed, and the rest is filled when they wake up in the morning.

Dim light melatonin onset (DLMO): DLMO will be assessed by collecting saliva samples every hour in the evening, starting from 19:00 until one hour after normal bedtime. DLMO samples will be collected one day before the intervention and the day after the intervention period. Saliva collection and analyses will follow procedures previously used by our research group. Blue light blocker glasses will be worn (from one hour prior to the first sample) in order to prevent melatonin suppression during saliva sampling. DLMO will be analyzed with enzyme-linked immunosorbent assay (ELISA) (direct saliva melatonin from Bühlmann Laboratories, Schöonenbuch, Switzerland). The analytical sensitivity of this kit is 0.5 pg/ml and functional sensitivity is 1.6-20.5 pg/ml, with an interassay coefficient of variation of \<12.6%. Samples will be analyzed with a Wallac plate reader from Perkin Elmer Inc. (Waltham, MA, USA).

Karolinska Sleepiness Scale (KSS): KSS comprises a single item assessing state sleepiness on a scale from 1 to 9. This instrument will be given in the laboratory on the days of the light intervention. It will be given for a total of six times per participant, twice on each intervention day, the first immediately when the participants come to the laboratory to receive the intervention, and the second after they have received one hour of light, before they leave the laboratory.

Psychomotor Vigilance Task (PVT): a 10-minute reaction-time test that provides a measure of sustained attention will be completed by the participants during light exposure in the laboratory. The participant simply responds to stimuli given on a display by pressing a button as soon as possible. PVT is especially sensitive to sleep loss and fatigue. PVT will be given to participants on the three days of light intervention.

Statistical analysis/power analysis:

A 2 (Time; pre vs post) x 2 (Group; blue vs. full spectrum light) ANOVA will be used for analyzing the results. Power analysis was conducted with G\*Power, version 3.17. Setting the effect size to medium (d=0.50), power to .80, alpha to .05, r between repeated measures to .50, shows that 34 participants will be needed in order to detect a significant Time x Group interaction.

Eligibility Criteria:
Inclusion Criteria:

* Scoring below 42 on the Horne-Östberg Morningness-Eveningness Questionnaire, as this categorizes moderate and definitely evening types (Horne \& Östberg, 1976).

Exclusion Criteria:

* Participants will be excluded if a positive case is indicated on the Mood Disorder Questionnaire (MDQ), indicating the presence or history of bipolar disorder.
* Participants will also be excluded if they have worked night shifts during the past three months.