Cross-sectional study of intraocular cataract lens replacement, circadian rest-activity rhythms, and sleep quality in older adults.

STUDY OBJECTIVES: Age-related cataract decreases light transmission at the most sensitive spectrum for circadian photoentrainment, with negative ramifications for human health. Here, we assessed whether intraocular lens replacement (IOL) in older patients with previous cataract was associated with increased stability and amplitude of circadian rest-activity rhythms, and improved sleep quality. METHODS: Our cross-sectional study included sixteen healthy older individuals without ocular diseases (controls; 55-80 years; 63.6 ± 5.6y; 8 women) and 13 patients with previous cataract and bilateral IOL (eight with blue-blocking [BB] lens and five with ultraviolet-only [UV] blocking lens; 55-80 years; 69.9 ± 5.2y; 9 women). The study comprised three weeks of at home rest-activity assessments using wrist-worn actigraphs, and each week preceded a laboratory protocol. Primary outcomes were actigraphy-derived interdaily stability, intradaily variability, and relative amplitude of circadian rest-activity rhythms. Secondary outcomes were actigraphy-assessed sleep quality (i.e. time in bed, sleep duration, sleep efficiency, mean wake bout time and fragmentation index). RESULTS: Patients with IOL had significantly higher interdaily stability ("Group" effect: pFDR =.001), but not intradaily variability ("Group" effect: pFDR = n.s.), and significantly higher relative amplitude of rest-activity rhythms ("Group" effect: pFDR < .001). Moreover, patients with IOL had significantly higher activity levels during the day and lower levels during the evening, as compared to healthy older controls ("Group" effect: pFDR = .03). Analyses of actigraphy-derived sleep parameters yielded no significant differences across groups ("Group" effect: all pFDR > .1). CONCLUSIONS: Our cross-sectional study suggests that enhancing spectral lens transmission in patients with cataract may benefit their circadian health.

Age-related neuroendocrine and alerting responses to light.

Aging is associated with sleep and circadian alterations, which can negatively affect quality of life and longevity. Importantly, the age-related reduction in light sensitivity, particularly in the short-wavelength range, may underlie sleep and circadian alterations in older people. While evidence suggests that non-image-forming (NIF) light responses may diminish in older individuals, most laboratory studies have low sample sizes, use non-ecological light settings (e.g., monochromatic light), and typically focus on melatonin suppression by light. Here, we investigated whether NIF light effects on endogenous melatonin levels and sleep frontal slow-wave activity (primary outcomes), and subjective sleepiness and sustained attention (secondary outcomes) attenuate with aging. We conducted a stringently controlled within-subject study with 3 laboratory protocols separated by ~ 1 week in 31 young (18-30 years; 15 women) and 16 older individuals (55-80 years; eight women). Each protocol included 2 h of evening exposure to commercially available blue-enriched polychromatic light (6500 K) or non-blue-enriched light (3000 K or 2500 K) at low levels (~ 40 lx, habitual in evening indoor settings). Aging significantly affected the influence of light on endogenous melatonin levels, subjective sleepiness, sustained attention, and frontal slow-wave activity (interaction: P < 0.001, P = 0.004, P = 0.007, P = 0.001, respectively). In young individuals, light exposure at 6500 K significantly attenuated the increase in endogenous melatonin levels, improved subjective sleepiness and sustained attention performance, and decreased frontal slow-wave activity in the beginning of sleep. Conversely, older individuals did not exhibit signficant differential light sensitivity effects. Our findings provide evidence for an association of aging and reduced light sensitivity, with ramifications to sleep, cognition, and circadian health in older people.

Intraocular cataract lens replacement and light exposure potentially impact procedural learning in older adults.

Procedural learning declines with age and appropriately timed light exposure can improve cognitive performance in older individuals. Because cataract reduces light transmission and is associated with cognitive decline in older adults, we explored whether lens replacement (intraocular blue-blocking [BB] or UV-only blocking) in older patients with cataracts enhances the beneficial effects of light on procedural learning. Healthy older participants (n = 16) and older patients with post-cataract surgery (n = 13 with BB or UV lens replacement) underwent a randomized within-subject crossover laboratory design with three protocols. In each protocol, 3.5 hr dim-dark adaptation was followed by 2 hr evening blue-enriched (6,500K) or non-blue-enriched light exposure (3,000K or 2,500K), 30 min dim post-light, ~8 hr sleep and 2 hr morning dim light. Procedural learning was assessed by the alternating serial reaction time task (ASRT), as part of a larger test battery. Here, ASRT performance was indexed by type of trial (random or sequence) and sequence-specific (high or low probability) measures. During evening light exposure, we observed a significant effect of the interaction of "group" versus "light condition" on the type of trial (p = .04; p = .16; unadjusted and adjusted p-values, respectively) and sequence-specific learning (p = .04; p = .16; unadjusted and adjusted p-values, respectively), whereby patients with UV lens replacement performed better than patients with BB lens or non-cataract controls, during blue-enriched light exposure. Lens replacement in patients with cataracts may potentially be associated with beneficial effects of blue light on procedural learning. Thus, optimizing spectral lens transmission in patients with cataracts may help improve specific aspects of cognitive function, such as procedural learning.

Effects of a dawn-dusk simulation on circadian rest-activity cycles, sleep, mood and well-being in dementia patients.

Light is the most powerful "zeitgeber" signal to synchronize circadian sleep-wake cycles. In dementia, these rhythms are often fragmented - probably due to loss of neuronal function of the suprachiasmatic nuclei (the biological "master clock" in the brain) and/or weakness of external zeitgebers. We investigated the effects of a prototype dawn-dusk simulator (DDS) on circadian rest-activity cycles, sleep, mood and well-being in a balanced crossover design during fall and winter in 20 institutionalized patients with dementia (86 ±â€¯6 y, 17 f). All participants had one baseline week followed by exposure to individually timed DDS over their beds for 7-8 weeks. They spent 8 weeks without DDS as a control. Mood, self-reliant daily activity, social behavior, agitation, and quality of life were assessed by standardized questionnaires and visual analogue scales, regularly rated by trained caregivers. Circadian and sleep characteristics of their rest-activity cycles were analyzed by actimetry over 17 weeks. DDS exposure led to significantly better mood in the morning hours after waking. The effects were most pronounced in the second 4 weeks with DDS, indicating that positive effects emerged gradually. Differences in circadian rest-activity cycles and sleep were mainly age-dependent. We found statistically significant correlations between measures of higher quality of life and better mood, greater alertness and circadian rhythm stability. We conclude that continuous, long-term application of dawn-dusk simulation at the sleep-wake transitions appears to increase external zeitgeber strength in institutionalized patients with dementia. The DDS may provide an effective, non-invasive tool to improve mood and ameliorate patients' quality of life.

Association of Intraocular Cataract Lens Replacement With Circadian Rhythms, Cognitive Function, and Sleep in Older Adults.

IMPORTANCE: Cataract is associated with a progressive decline in light transmission due to the clouding and yellowing of the natural crystalline lens. While the downstream effects of aging lenses include long-term disruption of circadian rhythms, cognitive function, and sleep regulation, it remains unknown whether there is an association of intraocular cataract lens (IOLs) replacement with circadian rhythms, cognition, and sleep. OBJECTIVE: To test whether IOL replacement (blue blocking [BB] or ultraviolet [UV] only blocking) in older patients with previous cataract is associated with the beneficial light effects on the circadian system, cognition, and sleep regulation. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study at the Centre for Chronobiology, University of Basel in Switzerland from February 2012 to April 2014, analyzed between June 2012 and September 2018. Sixteen healthy older controls and 13 patients with previous cataract and IOL replacement participated without medication and no medical and sleep comorbidities. EXPOSURES: Three and a half hours of prior light control (dim-dark adaptation), followed by 2 hours of evening blue-enriched (6500 K) or non-blue-enriched light exposure (3000 K and 2500 K), 30 minutes in dim post-light exposure, 8 hours of sleep opportunity, and 2 hours of morning dim light following sleep. MAIN OUTCOMES AND MEASURES: Salivary melatonin, cognitive tests, and sleep structure and electroencephalographic activity to test the association of IOLs with markers of circadian rhythmicity, cognitive performance, and sleep regulation, respectively. RESULTS: The participants included 16 healthy older controls with a mean (standard error of the mean [SEM]) of 63.6 (5.6) years; 8 women and 13 patients with previous cataract (mean [SEM] age, 69.9 [5.2] years; 10 women); 5 patients had UV IOLs and 8 had BB IOLs. Patients with previous cataract and IOLs had an attenuated increase in melatonin levels during light exposure (mean [SEM] increase in the BB group: 23.3% [2.6%] and in the UV lens group: 19.1% [2.1%]) than controls (mean [SEM] increase, 48.8% [5.2%]) (difference between means, 27.7; 95% CI, 15.4%-41.7%; P < .001). Cognitive function, indexed by sustained attention performance, was improved in patients with UV lens (mean [SEM], 276.9 [11.1] milliseconds) compared with patients with BB lens (mean [SEM], 348.3 [17.8] milliseconds) (difference between means, 71.4; 95% CI, 29.5%-113.1%; P = .002) during light exposure and in the morning after sleep. Patients with UV lens had increased slow-wave sleep (mean [SEM] increase, 13% [3.4%]) compared with controls (mean [SEM] increase, 5.2% [0.8%]) (percentage of total sleep time; difference between means, 7.9; 95% CI, 2.4%-13.4%; P = .02) and frontal non-rapid eye movement slow-wave activity (0.75-4.5 Hz) during the first sleep cycle (mean [SEM], 79.9 [13.6] µV2/Hz) compared with patients with BB lens (mean [SEM], 53.2 [10.7] µV2/Hz) (difference between means, 26.7; 95% CI, 9.2-48.9; P = .03). CONCLUSIONS AND RELEVANCE: These in-laboratory empirical findings suggest that optimizing the spectral lens transmission in patients with previous cataract may minimize the adverse age-related effects on circadian rhythms, cognition, and sleep.

Evaluation of Visual Comfort and Mental Effort Under Different Light Conditions for Ultraviolet-Absorbing and Additional Blue-Filtering Intraocular Lenses for Cataract Surgery.

PATIENTS AND METHODS: Patients with an ultraviolet blocking lens (UV) (n = 5) or blue filter lens (BB) (n = 8) after intraocular lens (IOL) replacement for cataract and age-adjusted controls (AACs) (n = 16) underwent a balanced crossover within-subject design. After 1.5 h of dark adaptation, they were exposed to polychromatic light at 6500 K (blue-enriched) and 2500 K and 3000 K (non-blue-enriched) for 2 hours in the evening. Visual comfort and mental effort were repeatedly assessed by the Visual Analogue Scale (0 - 100) and the Visual Comfort and Mental Effort Rating Scale (0 - 100) for each light condition. The results were compared using mixed model analysis. RESULTS: The mean (± SD) age for AAC and patients with UV or BB was 69.8 ± 6.2 y, 70.8 ± 4 y, and 63.6 ± 5.6 y, respectively. Irrespective of the light condition, patients with UV and BB felt mentally more tired during the experiments compared to AACs (F = 6.15, p = 0.003). However, patients with BB were mentally more motivated to perform the exercises compared to patients with UV and AACs (F = 8.1, p < 0.001). Patients with BB perceived ambient light as less glary (F = 4.71, p = 0.01) than patients with UV. Blue ambient light was felt less intensely in patients with BB (F = 2.51, p = 0.042) compared to those with UV and the AACs. CONCLUSION: Lens replacement in older cataract patients may increase visual comfort and minimize mental effort. While subtle, the magnitude of these effects may depend on the type of intraocular lens. BB intraocular lenses may have potential benefits, as ambient light is perceived as having less glare and less visual tension.

Non-24-Hour Sleep-Wake Disorder Revisited - A Case Study.

The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S), which rises linearly during the day, and a circadian process C, which determines the timing of sleep in a ~24-h rhythm in accordance to the external light-dark (LD) cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the suprachiasmatic nucleus ("master clock") of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation. While the phase length (tau) of the cycle is relatively stable and genetically determined, the phase of the clock is reset by external stimuli ("zeitgebers"), the most important being the LD cycle. Misalignments of the internal rhythm with the LD cycle can lead to various somatic complaints and to the development of circadian rhythm sleep disorders (CRSD). Non-24-hour sleep-wake disorders (N24HSWD) is a CRSD affecting up to 50% of totally blind patients and characterized by the inability to maintain a stable entrainment of the typically long circadian rhythm (tau > 24.5 h) to the LD cycle. The disease is rare in sighted individuals and the pathophysiology less well understood. Here, we present the case of a 40-year-old sighted male, who developed a misalignment of the internal clock with the external LD cycle following the treatment for Hodgkin's lymphoma (ABVD regimen, four cycles and AVD regimen, four cycles). A thorough clinical assessment, including actigraphy, melatonin profiles and polysomnography led to the diagnosis of non-24-hour sleep-wake disorders (N24HSWD) with a free-running rhythm of tau = 25.27 h. A therapeutic intervention with bright light therapy (30 min, 10,000 lux) in the morning and melatonin administration (0.5-0.75 mg) in the evening failed to entrain the free-running rhythm, although a longer treatment duration and more intense therapy might have been successful. The sudden onset and close timely connection led us to hypothesize that the chemotherapy might have caused a mutation of the molecular clock components leading to the observed elongation of the circadian period.

Blue blocker glasses as a countermeasure for alerting effects of evening light-emitting diode screen exposure in male teenagers.

PURPOSE: Adolescents prefer sleep and wake times that are considerably delayed compared with younger children or adults. Concomitantly, multimedia use in the evening is prevalent among teenagers and involves light exposure, particularly in the blue-wavelength range to which the biological clock and its associated arousal promotion system is the most sensitive. We investigated whether the use of blue light-blocking glasses (BB) during the evening, while sitting in front of a light-emitting diode (LED) computer screen, favors sleep initiating mechanisms at the subjective, cognitive, and physiological level. METHODS: The ambulatory part of the study comprised 2 weeks during which the sleep-wake cycle, evening light exposure, and multimedia screen use were monitored in thirteen 15- to 17-year-old healthy male volunteers. BB or clear lenses as control glasses were worn in a counterbalanced crossover design for 1 week each, during the evening hours while using LED screens. Afterward, participants entered the laboratory and underwent an evening blue light-enriched LED screen exposure during which they wore the same glasses as during the preceding week. Salivary melatonin, subjective sleepiness, and vigilant attention were regularly assayed, and subsequent sleep was recorded by polysomnography. RESULTS: Compared with clear lenses, BB significantly attenuated LED-induced melatonin suppression in the evening and decreased vigilant attention and subjective alertness before bedtime. Visually scored sleep stages and behavioral measures collected the morning after were not modified. CONCLUSIONS: BB glasses may be useful in adolescents as a countermeasure for alerting effects induced by light exposure through LED screens and therefore potentially impede the negative effects modern lighting imposes on circadian physiology in the evening.

[Circadian rhythm sleep disorders in psychiatric diseases]. / Störungen des Schlaf-Wach-Rhythmus bei psychiatrischen Erkrankungen.

Circadian rhythm sleep disorders are prevalent among psychiatric patients. This is most probable due to a close relationship between functional disturbances of the internal clock, sleep regulation and mental health. Mechanisms on molecular level of the circadian clock and neurotransmitter signalling are involved in the development of both disorders. Moreover, circadian disorders and psychiatric diseases favour each other by accessory symptoms such as stress or social isolation. Actimetry to objectively quantify the rest-activity cycle and salivary melatonin profiles as marker for the circadian phase help to diagnose circadian rhythm sleep disorders in psychiatric patients. Chronotherapeutics such as bright light therapy, dark therapy, melatonin administration, and wake therapy are used to synchronise and consolidate circadian rhythms and help in the treatment of depression and other psychiatric disorders, but are still neglected in medicine. More molecular to behavioural research is needed for the understanding of the development of circadian disorders and their relationship to psychiatric illnesses. This will help to boost the awareness and treatment of circadian rhythm sleep disorders in psychiatry.

Extraocular light via the ear canal does not acutely affect human circadian physiology, alertness and psychomotor vigilance performance.

We aimed at testing potential effects of extraocular bright light via the ear canals on human evening melatonin levels, sleepiness and psychomotor vigilance performance. Twenty healthy young men and women (10/10) kept a regular sleep-wake cycle during the 2-week study. The volunteers reported to the laboratory on three evenings, 2 h 15 min before usual bedtime, on average at 21:45 h. They were exposed to three different light conditions, each lasting for 12 min: extraocular bright light via the ear canal, ocular bright light as an active control condition and a control condition (extraocular light therapy device with completely blacked out LEDs). The timing of exposure was on average from 22:48 to 23:00 h. During the 2-h protocol, saliva samples were collected in 15-min intervals for melatonin assays along with subjective sleepiness ratings, and the volunteers performed a 10-min visual psychomotor vigilance task (PVT) prior to and after each light condition. The evening melatonin rise was significantly attenuated after the 12-min ocular bright light exposure while no significant changes were observed after the extraocular bright light and sham light condition. Subjective sleepiness decreased immediately over a short period only after ocular light exposure. No significant differences were observed for mean reaction times and the number of lapses for the PVT between the three light conditions. We conclude that extraocular transcranial light exposure in the late evening does not suppress melatonin, reduce subjective sleepiness or improve performance, and therefore, does not acutely influence the human circadian timing system.

Sleep and circadian rhythm dysregulation in schizophrenia.

Sleep-onset and maintenance insomnia is a common symptom in schizophrenic patients regardless of either their medication status (drug-naive or previously treated) or the phase of the clinical course (acute or chronic). Regarding sleep architecture, the majority of studies indicate that non-rapid eye movement (NREM), N3 sleep and REM sleep onset latency are reduced in schizophrenia, whereas REM sleep duration tends to remain unchanged. Many of these sleep disturbances in schizophrenia appear to be caused by abnormalities of the circadian system as indicated by misalignments of the endogenous circadian cycle and the sleep-wake cycle. Circadian disruption, sleep onset insomnia and difficulties in maintaining sleep in schizophrenic patients could be partly related to a presumed hyperactivity of the dopaminergic system and dysfunction of the GABAergic system, both associated with core features of schizophrenia and with signaling in sleep and wake promoting brain regions. Since multiple neurotransmitter systems within the CNS can be implicated in sleep disturbances in schizophrenia, the characterization of the neurotransmitter systems involved remains a challenging dilemma.

Circadian sleep-wake cycles, well-being, and light therapy in borderline personality disorder.

Individuals with borderline personality disorder (BPD) frequently suffer from sleep disturbances. The authors investigated circadian rhythms, sleep, and well-being in women with BPD in their habitual life conditions during 3 weeks with morning light therapy (LT) and 3 weeks without LT (oLT). Sleep-wake cycles were measured using wrist actimetry, proximal skin temperature as an indirect index of relaxation, as well as weekly salivary melatonin to document the internal circadian rhythm phase. Questionnaires assessed clinical state throughout the 6-week protocol. Ten matched healthy women followed the same 6-week protocol without light treatment. Women with BPD had significantly worse subjective sleep quality and reduced daytime alertness compared to controls. Sleep-wake cycles in BPD ranged from highly disturbed to extremely regular patterns. Melatonin and proximal skin temperature profiles revealed appropriate synchronization of the circadian system with the sleep-wake cycle in most BPD women and in all controls. Morning LT significantly phase-advanced activity in BPD compared to oLT, shortened sleep duration, decreased movement time, and increased skin temperature during sleep (a marker of relaxation). Although general depression scores and borderline symptoms did not change, daytime alertness improved with morning LT, and atypical depression scores were attenuated. Morning LT is a potential adjunct treatment for BPD.

Light and chronobiology: implications for health and disease.

Environmental light synchronizes the primary mammalian biological clock in the suprachiasmatic nuclei, as well as many peripheral clocks in tissues and cells, to the solar 24-hour day. Light is the strongest synchronizing agent (zeitgeber) for the circadian system, and therefore keeps most biological and psychological rhythms internally synchronized, which is important for optimum function. Circadian sleep-wake disruptions and chronic circadian misalignment, as often observed in psychiatric and neurodegenerative illness, can be treated with light therapy. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends on timing, intensity, and spectral composition of light exposure. Tailoring and optimizing indoor lighting conditions may be an approach to improve wellbeing, alertness, and cognitive performance and, in the long term, producing health benefits.

La luz ambiental sincroniza el reloj biológico primario de los mamíferos en el núcleo supraquiasmático, así como muchos relojes periféricos en tejídos y células, para el día solar de 24 horas. La luz es el agente sincronizador más potente (zeitgeber=dador de tiempo) para el sistema circadíano, y por consiguiente mantiene la mayoría de los ritmos biológicos y psicológicos que se sincronizan internamente, lo que es importante para una óptima función. Las disrupciones circadianas sueño-vigilia y los desajustes circadianos crónicos que se observan con frecuencía en enfermedades psiquiátricas y neurodegenerativas pueden ser tratados con fototerapía. Los efectos favorables sobre la sincronización circadíana, la calidad del sueño, el ánimo y el rendimiento cognitivo dependen de la duración, intensidad y composición espectral de la exposición a la luz. La adaptación y optímízacíón de las condíciones de luz interior pueden constituir una manera de mejorar el bienestar, el alerta y el rendimiento cognitivo, y a largo plazo producir beneficios para la salud.

La lumière environnementale synchronise l'horloge biologique primaire des mammifères dans le noyau suprachiasmatique, ainsi que de nombreuses horloges périphériques dans les tissus et les cellules, au jour solaire de 24 h. La lumière est l'agent synchronisant le plus fort (zeitgeber) du système circadien, conservant donc la plupart des rythmes biologiques et psychologiques synchronisés en interne, ce qui est important pour un fonctionnement optimal. Les troubles circadiens veille-sommeil et le décalage circadien chronique, souvent observés dans les maladies psychiatriques et neurodégénératives, peuvent être traités par luminothérapie. L'effet bénéfique sur la synchronisation circadienne, la qualité du sommeil, l'humeur et la performance cognitive dépend de la chronologie, de l'intensité et de la composition spectrale de l'exposition à la lumière. Personnaliser et optimiser les conditions de lumière en intérieur pourraient permettre d'améliorer le bien-être, la vigilance et la performance cognitive et, à long terme, être bénéfique pour la santé.

Sleep-wake cycles and cognitive functioning in schizophrenia.

BACKGROUND: Irregular sleep-wake cycles and cognitive impairment are frequently observed in schizophrenia, however, how they interact remains unclear. AIMS: To investigate the repercussions of circadian rhythm characteristics on cognitive performance and psychopathology in individuals with schizophrenia. METHOD: Fourteen middle-aged individuals diagnosed with schizophrenia underwent continuous wrist actimetry monitoring in real-life settings for 3 weeks, and collected saliva samples to determine the onset of endogenous melatonin secretion as a circadian phase marker. Moreover, participants underwent multiple neuropsychological testing and clinical assessments throughout the study period. RESULTS: Sleep-wake cycles in individuals with schizophrenia ranged from well entrained to highly disturbed rhythms with fragmented sleep epochs, together with delayed melatonin onsets and higher levels of daytime sleepiness. Participants with a normal rest-activity cycle (objectively determined by high relative amplitude of day/night activity) performed significantly better in frontal lobe function tasks. Stepwise regression analysis revealed that relative amplitude and age represented the best predictors for cognitive performance (Stroop colour-word interference task, Trail Making Test A and B, semantic verbal fluency task), whereas psychopathology (Positive and Negative Syndrome Scale) did not significantly correlate with either cognitive performance levels or the quality of sleep-wake cycles. CONCLUSIONS: Consolidated circadian rhythms and sleep may be a prerequisite for adequate cognitive functioning in individuals with schizophrenia.

Phase relationship between skin temperature and sleep-wake rhythms in women with vascular dysregulation and controls under real-life conditions.

The aim of the study was to investigate whether women with primary vascular dysregulation (VD; main symptoms of thermal discomfort with cold extremities) and difficulties initiating sleep (DIS) exhibit a disturbed phase of entrainment (Ψ) under everyday life conditions. The authors predicted a phase delay of the distal-proximal skin temperature gradient and salivary melatonin rhythms with respect to the sleep-wake cycle in women with VD and DIS (WVD) compared to controls (CON), similar to that found in their previous constant-routine laboratory data. A total of 41 young healthy women, 20 with WVD and 21 matched CON without VD and normal sleep onset latency (SOL), were investigated under ambulatory conditions (following their habitual bedtimes) during 7 days of continuous recording of skin temperatures, sleep-wake cycles monitored by actimetry and sleep-wake diaries, and single evening saliva collections for determining the circadian marker of dim light melatonin onset (DLMO). Compared to CON, WVD showed increased distal vasoconstriction at midday and in the evening, as indicated by lower distal (DIST; hands and feet) and foot-calf skin temperatures, and distal-proximal skin temperature gradients (p< .05). WVD manifested distal vasoconstriction before lights-off that also lasted longer after lights-off than in CON. In parallel, WVD exhibited a longer SOL (p< .05). To define internal phase-relationships, cross-correlation analyses were performed using diurnal rhythms of wrist activity and foot skin temperature. WVD showed a phase delay in foot skin temperature (CON versus WVD: 3.57 ± 17.28 min versus 38.50 ± 16.65 min; p< .05) but not in wrist activity. This finding was validated by additional within-subject cross-correlation analyses using the diurnal wrist activity pattern as reference. DLMO and habitual sleep times did not differ between CON and WVD. The authors conclude that WVD exhibit a phase delay of distal vasodilatation with respect to their habitual sleep-wake cycle and other circadian phase markers, such as DLMO. A full factorial design will have to show whether the finding is specific to primary vascular dysregulation, to DIS, or to their interaction.

Enhanced yolk testosterone influences behavioral phenotype independent of sex in Japanese quail chicks Coturnix japonica.

Studies have demonstrated an effect of yolk testosterone levels on the physiology and behavior of nestling birds. In order to investigate this phenomenon experimentally in a precocial bird, we enhanced yolk testosterone, but within the physiological range, by injecting 50 ng testosterone in ethanol into Japanese quail Coturnix japonica eggs prior to incubation. The chicks hatching from these as well as from control eggs that had received the carrier-only or were left unmanipulated were subject to a number of behavioral tests from hatching to the age of 3 weeks. In addition, fecal samples were taken during a 90-min isolation period to determine a physiological response to a stressor. Experimental chicks performed a detour task faster and approached novel objects sooner than did the controls. Chicks from treated eggs took a longer time to start distress vocalizing and also produced less distress calls during open-field trials, took on average a larger number of trials for them to show tonic immobility and also excreted lower levels of corticosterone metabolites (BM) than did the controls. In response to a stressor, excreted BM was initially higher in the control chicks, as compared to the experimental birds. Induced behavioral effects were independent of sex with no sex treatment interactions found. In sum, experimentally enhanced testosterone levels in the eggs shifted individual behavioral phenotype towards "bold" or "proactive", irrespective of sex. We conclude that testosterone in the yolk influences the coping style of hatchlings and may be a potential means of maternal influence on offspring phenotype.