Sarah Laxhmi Chellappa

Non-Visual Effects of Light on Melatonin, Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

Background Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance. Methods Sixteen healthy young men were studied in a balanced cross-over design with light exposure of 3 different light settings (compact fluorescent lamps with light of 40 lux at 6500K and at 2500K and incandescent lamps of 40 lux at 3000K) during 2 h in the evening. Results Exposure to light at 6500K induced greater melatonin suppression, together with enhanced subjective alertness, well-being and visual comfort. With respect to cognitive performance, light at 6500K led to significantly faster reaction times in tasks associated with sustained attention (Psychomotor Vigilance and GO/NOGO Task), but not in tasks associated with executive function (Paced Visual Serial Addition Task). This cognitive improvement was strongly related with attenuated salivary melatonin levels, particularly for the light condition at 6500K. Conclusions Our findings suggest that the sensitivity of the human alerting and cognitive response to polychromatic light at levels as low as 40 lux, is blue-shifted relative to the three-cone visual photopic system. Thus, the selection of commercially available compact fluorescent lights with different colour temperatures significantly impacts on circadian physiology and cognitive performance at home and in the workplace.

Acute exposure to evening blue-enriched light impacts on human sleep

Light in the short wavelength range (blue light: 446–483 nm) elicits direct effects on human melatonin secretion, alertness and cognitive performance via non‐image‐forming photoreceptors. However, the impact of blue‐enriched polychromatic light on human sleep architecture and sleep electroencephalographic activity remains fairly unknown. In this study we investigated sleep structure and sleep electroencephalographic characteristics of 30 healthy young participants (16 men, 14 women; age range 20–31 years) following 2 h of evening light exposure to polychromatic light at 6500 K, 2500 K and 3000 K. Sleep structure across the first three non‐rapid eye movement non‐rapid eye movement – rapid eye movement sleep cycles did not differ significantly with respect to the light conditions. All‐night non‐rapid eye movement sleep electroencephalographic power density indicated that exposure to light at 6500 K resulted in a tendency for less frontal non‐rapid eye movement electroencephalographic power density, compared to light at 2500 K and 3000 K. The dynamics of non‐rapid eye movement electroencephalographic slow wave activity (2.0–4.0 Hz), a functional index of homeostatic sleep pressure, were such that slow wave activity was reduced significantly during the first sleep cycle after light at 6500 K compared to light at 2500 K and 3000 K, particularly in the frontal derivation. Our data suggest that exposure to blue‐enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first non‐rapid eye movement episode.

Sleep disorders and suicidal ideation in patients with depressive disorder

An intrinsic association between suicidal ideation and sleep disorders in patients with depressive disorder has been observed in recent studies. This study was conducted in order to examine the relationship between suicidal ideation and sleep disorders, such as insomnia and excessive sleepiness, in outpatients with major depressive disorder. Seventy patients with diagnoses of major depressive disorder were interviewed and assessed with the Sleep Habits Questionnaire and the Beck Scale for Suicidal Ideation (SSI). Data analyses were performed through descriptive analysis, Students t-test, Chi-square test and logistic regression model, with a statistical significance of 5%. In this study, depressed patients had high SSI scores (6.12+/-2.67), particularly for active suicidal ideation (1.61+/-0.39) and specific plans for suicide components (1.51+/-0.40). Depressed patients with insomnia had significantly higher SSI scores (7.39+/-2.84), in relation to patients with excessive sleepiness (3.68+/-1.73). Furthermore it was observed that insomniac patients had significantly higher scores on the following components: active suicide ideation, specific plans for suicide and previous suicide attempts. The results of multivariate analysis showed that only insomnia had a significant association with suicidal ideation. Thus, sleep disturbances, particularly insomnia, should be considered in the assessment of suicidal risk in outpatients with depressive disorder.

Can light make us bright? : Effects of light on cognition and sleep

Light elicits robust nonvisual effects on numerous physiological and behavioral variables, such as the human sleep-wake cycle and cognitive performance. Light effects crucially rely on properties such as dose, duration, timing, and wavelength. Recently, the use of methods such as fMRI to assess light effects on nonvisual brain responses has revealed how light can optimize brain function during specific cognitive tasks, especially in tasks of sustained attention. In this chapter, we address two main issues: how light impinges on cognition via consolidation of human sleep-wake cycles; and how light directly impacts on sleep and cognition, in particular in tasks of sustained attention. A thorough understanding of how light affects sleep and cognitive performance may help to improve light settings at home and at the workplace in order to improve well-being.

Excessive daytime sleepiness in patients with depressive disorder

OBJECTIVE To evaluate excessive daytime sleepiness in patients with depressive disorder and to examine its association with the severity of depression and suicidal ideation. METHOD Seventy patients were interviewed and assessed by the Epworth Sleepiness Scale (ESS), the Beck Depression Inventory (BDI) and the Beck Scale for Suicidal Ideation (SSI). Descriptive analysis, Pearson correlations and Students t-test were used for data analyses. RESULTS Most of the patients (57.1%) obtained high scores on the ESS. Correlation was positive and strongly significant between ESS scores and BDI scores, as well as between ESS scores and SSI scores. Patients with high ESS scores obtained higher mean BDI and SSI scores in comparison to patients with lower ESS scores. Significant differences (p < 0.05) were encountered when the patients with higher (> or = 10) and lower (< 10) ESS scores were compared in terms of total ESS, BDI and SSI scores. CONCLUSIONS Excessive daytime sleepiness was frequent among patients and significantly associated with higher levels of depression and particularly with suicidal ideation. Thus, a careful investigation of daytime sleepiness in depressed patients is required during clinical evaluation.

Human Melatonin and Alerting Response to Blue-Enriched Light Depend on a Polymorphism in the Clock Gene PER3

CONTEXT Light exposure, particularly at the short-wavelength range, triggers several nonvisual responses in humans. However, the extent to which the melatonin-suppressing and alerting effect of light differs among individuals remains unknown. OBJECTIVE Here we investigated whether blue-enriched polychromatic light impacts differentially on melatonin and subjective and objective alertness in healthy participants genotyped for the PERIOD3 (PER3) variable-number, tandem-repeat polymorphism. DESIGN, SETTING, AND PARTICIPANTS Eighteen healthy young men homozygous for the PER3 polymorphism (PER3(5/5)and PER3(4/4)) underwent a balanced crossover design during the winter season, with light exposure to compact fluorescent lamps of 40 lux at 6500 K and at 2500 K during 2 h in the evening. RESULTS In comparison to light at 2500 K, blue-enriched light at 6500 K induced a significant suppression of the evening rise in endogenous melatonin levels in PER3(5/5) individuals but not in PER3(4/4). Likewise, PER3(5/5) individuals exhibited a more pronounced alerting response to light at 6500 K than PER3(4/4) volunteers. Waking electroencephalographic activity in the theta range (5-7 Hz), a putative correlate of sleepiness, was drastically attenuated during light exposure at 6500 K in PER3(5/5) individuals as compared with PER3(4/4). CONCLUSIONS We provide first evidence that humans homozygous for the PER3 5/5 allele are particularly sensitive to blue-enriched light, as indexed by the suppression of endogenous melatonin and waking theta activity. Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in the sleep-wake regulation.

Effects of Artificial Dawn and Morning Blue Light on Daytime Cognitive Performance, Well-being, Cortisol and Melatonin Levels

Light exposure elicits numerous effects on human physiology and behavior, such as better cognitive performance and mood. Here we investigated the role of morning light exposure as a countermeasure for impaired cognitive performance and mood under sleep restriction (SR). Seventeen participants took part of a 48h laboratory protocol, during which three different light settings (separated by 2 wks) were administered each morning after two 6-h sleep restriction nights: a blue monochromatic LED (light-emitting diode) light condition (BL; 100 lux at 470 nm for 20 min) starting 2 h after scheduled wake-up time, a dawn-simulating light (DsL) starting 30 min before and ending 20 min after scheduled wake-up time (polychromatic light gradually increasing from 0 to 250 lux), and a dim light (DL) condition for 2 h beginning upon scheduled wake time (<8 lux). Cognitive tasks were performed every 2 h during scheduled wakefulness, and questionnaires were administered hourly to assess subjective sleepiness, mood, and well-being. Salivary melatonin and cortisol were collected throughout scheduled wakefulness in regular intervals, and the effects on melatonin were measured after only one light pulse. Following the first SR, analysis of the time course of cognitive performance during scheduled wakefulness indicated a decrease following DL, whereas it remained stable following BL and significantly improved after DsL. Cognitive performance levels during the second day after SR were not significantly affected by the different light conditions. However, after both SR nights, mood and well-being were significantly enhanced after exposure to morning DsL compared with DL and BL. Melatonin onset occurred earlier after morning BL exposure, than after morning DsL and DL, whereas salivary cortisol levels were higher at wake-up time after DsL compared with BL and DL. Our data indicate that exposure to an artificial morning dawn simulation light improves subjective well-being, mood, and cognitive performance, as compared with DL and BL, with minimal impact on circadian phase. Thus, DsL may provide an effective strategy for enhancing cognitive performance, well-being, and mood under mild sleep restriction.

Interindividual differences in circadian rhythmicity and sleep homeostasis in older people: effect of a PER3 polymorphism.

Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3(5/5)) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3(5/5) participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3(4/4) participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people.

HUMAN SLEEP AND COGNITION, PT II: CLINICAL AND APPLIED RESEARCH

Light elicits robust nonvisual effects on numerous physiological and behavioral variables, such as the human sleep-wake cycle and cognitive performance. Light effects crucially rely on properties such as dose, duration, timing, and wavelength. Recently, the use of methods such as fMRI to assess light effects on nonvisual brain responses has revealed how light can optimize brain function during specific cognitive tasks, especially in tasks of sustained attention. In this chapter, we address two main issues: how light impinges on cognition via consolidation of human sleep-wake cycles; and how light directly impacts on sleep and cognition, in particular in tasks of sustained attention. A thorough understanding of how light affects sleep and cognitive performance may help to improve light settings at home and at the workplace in order to improve well-being.

Chronobiology, excessive daytime sleepiness and depression: Is there a link?

The complaint of excessive daytime sleepiness (EDS), commonly encountered in clinical practice, may arise from a variety of psychiatric disorders, most importantly depression. Even though EDS frequently leads depressed patients to seek medical assistance, it is commonly under-evaluated and under-diagnosed. Therefore, a comprehensive understanding and management of EDS is essential in the clinical assessment of depression. Within a theoretical framework, a chronobiological approach may shed new light on the complex interaction of EDS and depression. In this review, studies on EDS and depression are summarized and discussed within the context of circadian and sleep regulatory mechanisms. Furthermore, potential chronobiological therapeutic strategies are proposed to address some of the unmet needs in the treatment of EDS and depression.