Professor Debra J. Skene

Featured Stories

Research Interests

Circadian rhythms in the blind, effect of visual loss and visual pathologies

Characterisation and treatment of circadian rhythm disorders as experienced by blind people, shift workers, transmeridian air travellers and older people

Role of endogenous and exogenous melatonin in circadian rhythm sleep disorders

Investigation of circadian photoentrainment (optimum characteristics of light and melatonin) in humans

Non visual light responses and characteristics of the circadian photoreception pathway in humans; age-related changes in the circadian timing system; effect of light on sleep, activity and the clock

Human circadian rhythms, sleep and metabolism in health, circadian disorders and metabolic diseases (shift workers, Type 2 diabetes, liver disease).

Departmental Duties

Leader of the Sleep, Chronobiology and Addiction Research Group

Leader of the Metabolomics Core Technology 

Module Organiser, BS346 Biological Rhythms

Honours

Royal Society Wolfson Research Merit Award
Linking light, circadian rhythms, sleep and metabolism in health and disease
2011 - 2016

Chair, Gordon Research Conference on Pineal Cell Biology: Links to clocks, sleep and metabolism, Hotel Galvez, Galveston, Texas, USA, 29th January -3rd February, 2012.

Professional Activities

President of the European Biological Rhythms Society (EBRS), 2015 – (previously Secretary-Treasurer, 2005-2009; Vice-President, 2012-2015).
Past Vice-President (Basic), European Sleep Research Society (ESRS), 2010 – 2014 (previously Assistant Secretary, 2006-2010).

EDITORIAL BOARDS

Editorial Board, Chronobiology International, 2007 -
Associate Editor, Journal of Sleep Research, 2008 -
Advisory Board, Sleep and Biological Rhythms, 2012 –

Co-Director, Stockgrand Ltd.
Interested in measuring melatonin/6-sulphatoxymelatonin? Visit our website.

RESEARCH GRANT FUNDING, 2005 -  (over £100K)

EU FP6 (Marie Curie Research Training Networks), The biomedical and sociological effects of sleep restriction, 2005-2009, Surrey PI, £1,009,228.

EU FP6 (Integrated Project) EUCLOCK, Entrainment of the circadian clock, 2006-2011, Surrey PI, 455,898 euros.

Cross-Council New Dynamics of Ageing (NDA) Initiative, a multidisciplinary research programme supported by AHRC, BBSRC, EPSRC, ESRC and MRC, SomnIA, Optimising quality of sleep among older people in the community and care homes: An integrated approach, 2006-2011, Co-I, £1,892,973.

BBSRC, Food entrainment of the human circadian timing system, 2011 – 2014, Co-I, £1,203,397 (fEC).

BBSRC, Effect of the circadian clock time of day and sleep on the human metabolome:
identification of metabolite rhythms, 2011-2014, PI, £948,715 (fEC).

EU FP7-HEALTH-2011, EuRhythDia, Impact of lifestyle interventions on diabetogenic and atherogenic effects of changes in diurnal rhythm, 2011 – 2016, Surrey PI, 166,277 euros.

Contact Me

E-mail:
Phone: 01483 68 9706

Find me on campus
Room: 16 AY 02

Publications

Highlights

  • Giskeodegard GF, Davies SK, Revell VL, Keun H, Skene DJ. (2015) 'Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation'. NATURE PUBLISHING GROUP SCIENTIFIC REPORTS, 5 Article number ARTN 14843
  • Moreno CRC, Vasconcelos S, Marqueze EC, Lowden A, Middleton B, Fischer M, Louzada FM, Skene DJ. (2015) 'Sleep patterns in Amazon rubber tappers with and without electric light at home'. NATURE PUBLISHING GROUP SCIENTIFIC REPORTS, 5 Article number ARTN 14074
  • Davies SK, Ang JE, Revell VL, Holmes B, Mann A, Robertson FP, Cui N, Middleton B, Ackermann K, Kayser M, Thumser AE, Raynaud FI, Skene DJ. (2014) 'Effect of sleep deprivation on the human metabolome'. NATL ACAD SCIENCES PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111 (29), pp. 10761-10766.
  • Lucas RJ, Brown TM, Peirson SN, Berson DM, Cooper HM, Czeisler CA, Lockley SW, Figueiro MG, Gamlin PD, O'Hagan JB, Price LLA, Provencio I, Skene DJ, Brainard GC. (2014) 'Measuring and using light in the melanopsin age'. Trends in Neurosciences, 37 (1), pp. 1-9.
  • Ackermann K, Plomp R, Lao O, Middleton B, Revell VL, Skene DJ, Kayser M. (2013) 'Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans.'. Informa Healthcare Chronobiol Int, England: 30 (7), pp. 901-909.

    Abstract

    This study investigated the impact of sleep deprivation on the human circadian system. Plasma melatonin and cortisol levels and leukocyte expression levels of 12 genes were examined over 48 h (sleep vs. no-sleep nights) in 12 young males (mean ± SD: 23 ± 5 yrs). During one night of total sleep deprivation, BMAL1 expression was suppressed, the heat shock gene HSPA1B expression was induced, and the amplitude of the melatonin rhythm increased, whereas other high-amplitude clock gene rhythms (e.g., PER1-3, REV-ERBα) remained unaffected. These data suggest that the core clock mechanism in peripheral oscillators is compromised during acute sleep deprivation.

  • Ang JE, Revell V, Mann A, Mäntele S, Otway DT, Johnston JD, Thumser AE, Skene DJ, Raynaud F. (2012) 'Identification of Human Plasma Metabolites Exhibiting Time-of-Day Variation Using an Untargeted Liquid Chromatography-Mass Spectrometry Metabolomic Approach.'. Informa Healthcare Chronobiol Int, England: 29 (7), pp. 868-881.

    Abstract

    Although daily rhythms regulate multiple aspects of human physiology, rhythmic control of the metabolome remains poorly understood. The primary objective of this proof-of-concept study was identification of metabolites in human plasma that exhibit significant 24-h variation. This was assessed via an untargeted metabolomic approach using liquid chromatography-mass spectrometry (LC-MS). Eight lean, healthy, and unmedicated men, mean age 53.6 (SD ± 6.0) yrs, maintained a fixed sleep/wake schedule and dietary regime for 1 wk at home prior to an adaptation night and followed by a 25-h experimental session in the laboratory where the light/dark cycle, sleep/wake, posture, and calorific intake were strictly controlled. Plasma samples from each individual at selected time points were prepared using liquid-phase extraction followed by reverse-phase LC coupled to quadrupole time-of-flight MS analysis in positive ionization mode. Time-of-day variation in the metabolites was screened for using orthogonal partial least square discrimination between selected time points of 10:00 vs. 22:00 h, 16:00 vs. 04:00 h, and 07:00 (d 1) vs. 16:00 h, as well as repeated-measures analysis of variance with time as an independent variable. Subsequently, cosinor analysis was performed on all the sampled time points across the 24-h day to assess for significant daily variation. In this study, analytical variability, assessed using known internal standards, was low with coefficients of variation <10%. A total of 1069 metabolite features were detected and 203 (19%) showed significant time-of-day variation. Of these, 34 metabolites were identified using a combination of accurate mass, tandem MS, and online database searches. These metabolites include corticosteroids, bilirubin, amino acids, acylcarnitines, and phospholipids; of note, the magnitude of the 24-h variation of these identified metabolites was large, with the mean ratio of oscillation range over MESOR (24-h time series mean) of 65% (95% confidence interval [CI]: 49-81%). Importantly, several of these human plasma metabolites, including specific acylcarnitines and phospholipids, were hitherto not known to be 24-h variant. These findings represent an important baseline and will be useful in guiding the design and interpretation of future metabolite-based studies. (Author correspondence: Jooern.Ang@icr.ac.uk or Florence.Raynaud@icr.ac.uk ).

  • Ackermann K, Revell VL, Lao O, Rombouts EJ, Skene DJ, Kayser M. (2012) 'Diurnal rhythms in blood cell populations and the effect of acute sleep deprivation in healthy young men.'. Sleep, United States: 35 (7), pp. 933-940.

    Abstract

    The sleep/wake cycle is accompanied by changes in circulating numbers of immune cells. The goal of this study was to provide an in-depth characterization of diurnal rhythms in different blood cell populations and to investigate the effect of acute sleep deprivation on the immune system, as an indicator of the body's acute stress response.

  • Wehrens SM, Hampton SM, Skene DJ. (2012) 'Heart rate variability and endothelial function after sleep deprivation and recovery sleep among male shift and non-shift workers.'. Scandinavian Journal of Work, Environmental & Health Scandinavian Journal of Work, Environmental & Health, 38 (12), pp. 171-181.

    Abstract

    OBJECTIVES: Endothelial dysfunction and alterations in heart rate variability (HRV) as well as sleep deprivation and shift work have been associated with cardiovascular disease. The aim of this study was to compare HRV and endothelial function among shift and matched non-shift workers in response to total sleep deprivation and recovery sleep under identical laboratory settings. METHODS: Eleven experienced male shift workers (shift work ≥5 years) and 14 non-shift workers were matched for age, body mass index, and cholesterol. HRV parameters [eg, HR variance and low frequency/high frequency (LF/HF) ratio] were derived from 5-minute electrocardiogram bins at 0.25, 4.25, 11.5, 12.5, and 13.5 hours after habitual wake-up time and endothelial function was assessed by flow-mediated dilatation (FMD) using ultrasound at 0.75 and 10.75 hours after habitual wake-up time, following baseline sleep, total sleep deprivation, and recovery sleep (posture- and food-controlled throughout). Circadian phase was assessed before baseline sleep by salivary dim light melatonin onset. RESULTS: There was no difference in circadian phase between shift and non-shift workers. HR variance was highest at 0.25 hours following total sleep deprivation and lowest after recovery sleep. A significantly higher LF/HF ratio, significantly lower HR variance, and a trend for a lower %FMD (P=0.08) were observed among shift compared to non-shift workers. CONCLUSION: Despite similar demographics, circadian phase, posture and food intake, differences in endothelial function and HRV were observed in the two groups, which may reflect higher sympathetic and/or lower parasympathetic activity, contributing to increased cardiovascular risk among the shift workers.

  • Otway DT, Mäntele S, Bretschneider S, Wright J, Trayhurn P, Skene DJ, Robertson MD, Johnston JD. (2011) 'Rhythmic Diurnal Gene Expression in Human Adipose Tissue From Individuals Who Are Lean, Overweight, and Have Type 2 Diabetes.'. Diabetes,
  • Sletten TL, Revell VL, Middleton B, Lederle KA, Skene DJ. (2009) 'Age-Related Changes in Acute and Phase-Advancing Responses to Monochromatic Light'. SAGE PUBLICATIONS INC JOURNAL OF BIOLOGICAL RHYTHMS, 24 (1), pp. 73-84.
  • Viola AU, Archer SN, James LM, Groeger JA, Lo JCY, Skene DJ, von Schantz M, Dijk D-J. (2007) 'PER3 polymorphism predicts sleep structure and waking performance'. CELL PRESS CURRENT BIOLOGY, 17 (7), pp. 613-618.
  • Revell VL, Arendt J, Louis FF, Skene DJ. (2006) 'Alerting effects of light are sensitive to very short wavelengths'. ELSEVIER IRELAND LTD NEUROSCIENCE LETTERS, 399 (1-2), pp. 96-100.
  • Thapan K, Arendt J, Skene DJ. (2001) 'An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans'. CAMBRIDGE UNIV PRESS J PHYSIOL-LONDON, 535 (1), pp. 261-267.
  • Lockley SW, Skene DJ, James K, Thapan K, Wright J, Arendt J. (2000) 'Melatonin administration can entrain the free-running circadian system of blind subjects'. SOC ENDOCRINOLOGY JOURNAL OF ENDOCRINOLOGY, 164 (1), pp. R1-R6.
  • Lockley SW, Skene DJ, Arendt J, Tabandeh H, Bird AC, Defrance R. (1997) 'Relationship between melatonin rhythms and visual loss in the blind'. ENDOCRINE SOC J CLIN ENDOCR METAB, 82 (11), pp. 3763-3770.

    Abstract

    Melatonin rhythms were assessed in 49 registered blind individuals by measurement of the urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s). Subjects had different causes of visual loss and were classified as having light perception or better (LP; n 5 19) or having no perception of light (NPL; n 5 30). Subjects collected four-hourly urine samples (eight-hourly overnight) for 48 h at weekly intervals for 3–5 weeks. The majority of LP subjects (14 of 19) had normally entrained aMT6s rhythms (mean acrophase range, 2.4–6.2 h), 4 were abnormally entrained to 24 h (mean acrophase range, 8.9–1.0 h), and 1 was unclassified. Conversely, mostNPLsubjects had abnormal rhythms (23 of 30), the incidence of which was greater in uni- and bilaterally enucleated subjects. The majority of NPL subjects (17 of 30) had free-running aMT6s rhythms (period range, 24.13– 24.79 h), 5 were abnormally entrained to 24 h (acrophase range, 7.2–20.6 h), and 1 was unclassified. Output (micrograms of aMT6s per 24 h) and amplitude (micrograms per h) of aMT6s production did not vary between LP and NPL subjects (mean 24-h output 6 SD, 12.7 6 7.5 and 9.4 6 6.4 mg aMT6s/24 h, respectively; mean amplitude 6 SD, 0.660.4 and 0.560.3 mg/h, respectively). These results indicate that a higher proportion of NPL subjects have abnormal melatonin rhythms compared to those with LP. (J Clin Endocrinol Metab 82: 3763–3770, 1997)

  • SKENE DJ, BOJKOWSKI CJ, CURRIE JE, WRIGHT J, BOULTER PS, ARENDT J. (1990) '6-SULPHATOXYMELATONIN PRODUCTION IN BREAST-CANCER PATIENTS'. MUNKSGAARD INT PUBL LTD JOURNAL OF PINEAL RESEARCH, 8 (3), pp. 269-276.

Journal articles

  • de la Iglesia HO, Moreno C, Lowden A, Louzada F, Marqueze E, Levandovski R, Pilz LK, Valeggia C, Fernandez-Duque E, Golombek DA, Czeisler CA, Skene DJ, Duffy JF, Roenneberg T. (2016) 'Ancestral sleep.'. Curr Biol, England: 26 (7), pp. R271-R272.
  • Lech K, Liu F, Ackermann K, Revell VL, Lao O, Skene DJ, Kayser M. (2016) 'Evaluation of mRNA markers for estimating blood deposition time: Towards alibi testing from human forensic stains with rhythmic biomarkers'. ELSEVIER IRELAND LTD FORENSIC SCIENCE INTERNATIONAL-GENETICS, 21, pp. 119-125.
  • Lech K, Ackermann K, Revell VL, Lao O, Skene DJ, Kayser M. (2016) 'Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood'. SAGE PUBLICATIONS INC JOURNAL OF BIOLOGICAL RHYTHMS, 31 (1), pp. 68-81.
  • Gunn PJ, Middleton B, Davies SK, Revell VL, Skene DJ. (2016) 'Sex differences in the circadian profiles of melatonin and cortisol in plasma and urine matrices under constant routine conditions'. TAYLOR & FRANCIS INC CHRONOBIOLOGY INTERNATIONAL, 33 (1), pp. 39-50.

    Abstract

    Conflicting evidence exists as to whether there are differences between males and females in circadian timing. The aim of the current study was to assess whether sex differences are present in the circadian regulation of melatonin and cortisol in plasma and urine matrices during a constant routine protocol. Thirty-two healthy individuals (16 females taking the oral contraceptive pill (OCP)), aged 23.8 ± 3.7 (mean ± SD) years, participated. Blood (hourly) and urine (4-hourly) samples were collected for measurement of plasma melatonin and cortisol, and urinary 6-sulfatoxymelatonin (aMT6s) and cortisol, respectively. Data from 28 individuals (14 females) showed no significant differences in the timing of plasma and urinary circadian phase markers between sexes. Females, however, exhibited significantly greater levels of plasma melatonin and cortisol than males (AUC melatonin: 937 ± 104 (mean ± SEM) vs. 642 ± 47 pg/ml.h; AUC cortisol: 13581 ± 1313 vs. 7340 ± 368 mmol/L.h). Females also exhibited a significantly higher amplitude rhythm in both hormones (melatonin: 43.8 ± 5.8 vs. 29.9 ± 2.3 pg/ml; cortisol: 241.7 ± 23.1 vs. 161.8 ± 15.9 mmol/L). Males excreted significantly more urinary cortisol than females during the CR (519.5 ± 63.8 vs. 349.2 ± 39.3 mol) but aMT6s levels did not differ between sexes. It was not possible to distinguish whether the elevated plasma melatonin and cortisol levels observed in females resulted from innate sex differences or the OCP affecting the synthetic and metabolic pathways of these hormones. The fact that the sex differences observed in total plasma concentrations for melatonin and cortisol were not reproduced in the urinary markers challenges their use as a proxy for plasma levels in circadian research, especially in OCP users.

  • Giskeodegard GF, Davies SK, Revell VL, Keun H, Skene DJ. (2015) 'Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation'. NATURE PUBLISHING GROUP SCIENTIFIC REPORTS, 5 Article number ARTN 14843
  • Moreno CRC, Vasconcelos S, Marqueze EC, Lowden A, Middleton B, Fischer M, Louzada FM, Skene DJ. (2015) 'Sleep patterns in Amazon rubber tappers with and without electric light at home'. NATURE PUBLISHING GROUP SCIENTIFIC REPORTS, 5 Article number ARTN 14074
  • Johnston JD, Skene DJ. (2015) '60 YEARS OF NEUROENDOCRINOLOGY: Regulation of mammalian neuroendocrine physiology and rhythms by melatonin.'. J Endocrinol, England: 226 (2), pp. T187-T198.
  • Bonmati-Carrion MA, Middleton B, Revell VL, Skene DJ, Rol MA, Madrid JA. (2015) 'Validation of an innovative method, based on tilt sensing, for the assessment of activity and body position.'. Chronobiol Int, 32 (5), pp. 701-710.
  • Papantoniou K, Pozo OJ, Espinosa A, Marcos J, Castaño-Vinyals G, Basagaña X, Juanola Pagès E, Mirabent J, Martín J, Such Faro P, Gascó Aparici A, Middleton B, Skene DJ, Kogevinas M. (2015) 'Increased and mistimed sex hormone production in night shift workers.'. Cancer Epidemiol Biomarkers Prev, United States: 24 (5), pp. 854-863.

    Abstract

    BACKGROUND: Night shift work has been associated with an increased risk for breast and prostate cancer. The effect of circadian disruption on sex steroid production is a possible underlying mechanism, underinvestigated in humans. We have assessed daily rhythms of sex hormones and melatonin in night and day shift workers of both sexes. METHODS: We recruited 75 night and 42 day workers, ages 22 to 64 years, in different working settings. Participants collected urine samples from all voids over 24 hours on a working day. Urinary concentrations of 16 sex steroid hormones and metabolites (estrogens, progestagens, and androgens) and 6-sulfatoxymelatonin were measured in all samples. Mean levels and peak time of total and individual metabolite production were compared between night and day workers. RESULTS: Night workers had higher levels of total progestagens [geometric mean ratio (GMR) 1.65; 95% confidence intervals (CI), 1.17-2.32] and androgens (GMR: 1.44; 95% CI, 1.03-2.00), compared with day workers, after adjusting for potential confounders. The increased sex hormone levels among night shift workers were not related to the observed suppression of 6-sulfatoxymelatonin. Peak time of androgens was significantly later among night workers, compared with day workers (testosterone: 12:14 hours; 10:06-14:48 vs. 08:35 hours; 06:52-10:46). CONCLUSIONS: We found increased levels of progestagens and androgens as well as delayed peak androgen production in night shift workers compared with day workers. IMPACT: The increase and mistiming of sex hormone production may explain part of the increased risk for hormone-related cancers observed in night shift workers.

  • Gringras P, Middleton B, Skene DJ, Revell VL. (2015) 'Bigger, Brighter, Bluer-Better? Current Light-Emitting Devices - Adverse Sleep Properties and Preventative Strategies.'. Frontiers Media Frontiers in public health, 3, pp. 233-233.
  • Marqueze EC, Vasconcelos S, Garefelt J, Skene DJ, Moreno CR, Lowden A. (2015) 'Natural light exposure, sleep and depression among day workers and shiftworkers at arctic and equatorial latitudes.'. PLoS One, United States: 10 (4)

    Abstract

    OBJECTIVES: This study aimed to investigate the relationship between individual natural light exposure, sleep need, and depression at two latitudes, one extreme with a few hours of light per day during winter, and the other with equal hours of light and darkness throughout the year. METHODS: This cross-sectional study included a sample of Brazilian workers (Equatorial, n = 488 workers) and a Swedish sample (Arctic, n = 1,273). RESULTS: The reported mean total natural light exposure per 4-week cycle differed significantly between the Equatorial and Arctic regions. However, shiftworkers from both sites reported similar hours of natural light exposure. Short light exposure was a predictor for insufficient sleep. CONCLUSION: Reduced exposure to natural light appears to increase the perception of obtaining insufficient sleep. Arctic workers were more prone to develop depression than Equatorial workers.

  • Fischer FM, Puttonen S, Skene DJ. (2014) '21st International symposium on shiftwork and working time: the 24/7 society--from chronobiology to practical life.'. Chronobiol Int, England: 31 (10), pp. 1093-1099.
  • Montagnese S, Middleton B, Corrias M, Mani AR, Skene DJ, Morgan MY. (2014) 'Assessment of 6-sulfatoxymelatonin rhythms and melatonin response to light in disease states: lessons from cirrhosis.'. Chronobiol Int, England: 32 (2), pp. 187-194.

    Abstract

    Circadian rhythmicity and non-visual sensitivity to light can be assessed, in healthy subjects, by measuring the rhythm of the urinary melatonin metabolite 6-sulphatoxymelatonin (aMT6s) and by determining the response of plasma melatonin to nocturnal retinal light exposure, respectively. However, the validity of these techniques has not been assessed in disease states in which disruption of the circadian rhythm is known or suspected to occur. Thus, the aims of this study were as follows: (i) to assess the reliability of circadian aMT6s profile estimates derived from 36 h versus 56 h urine collections and (ii) to test different models for calculating melatonin suppression in response to light in healthy volunteers and patients with cirrhosis. Twenty patients with biopsy-proven cirrhosis and 10 matched healthy volunteers undertook: (i) separate 36 - and 56-h urine collections, under controlled conditions, for cosinor analysis of the urinary aMT6s profile; (ii) a melatonin suppression test, comprising of a baseline night, during which subjects were woken and asked to sit in front of a switched off light sphere, and an experimental night, identically executed, except that the light sphere was switched on and the subjects were exposed to white light (4.1 × 10(14) photons/cm(2)/s) for 30 min. Alternative approaches to the calculation of melatonin suppression were taken, with/without inclusion of the baseline night. Eighteen patients and eight healthy volunteers had matched analysable 36 - and 56-h urinary samples. Cosinor analysis showed a significant fit in 88% of the remaining 56 h collections, and 48% of the remaining 36-h collections. Thus, eight patients and five healthy volunteers had matched analysable samples for cosinor analysis. In the healthy volunteers, aMT6s profile indices obtained using the 36 - and the 56-h collections did not differ significantly. In contrast, considerably more variability was observed in patients [i.e. the difference in the aMT6s peak time was 0.5 ± 1.7 h (limits of agreement: -3.9; +2.9 h)]. No difficulties were encountered in obtaining suppression estimates by use of the experimental night only. In contrast, suppression estimates obtained by use of both nights were considered inaccurate in one (11%) healthy volunteer and in 5 (28%) patients, primarily because: (i) melatonin concentrations at the beginning of light administration were significantly different on baseline and experimental night; (ii) the rise in melatonin was in

  • Kantermann T, Duboutay F, Haubruge D, Hampton S, Darling AL, Berry JL, Kerkhofs M, Boudjeltia KZ, Skene DJ. (2014) 'The direction of shift-work rotation impacts metabolic risk independent of chronotype and social jetlag--an exploratory pilot study.'. Chronobiol Int, England: 31 (10), pp. 1139-1145.
  • De Rui M, Middleton B, Sticca A, Gatta A, Amodio P, Skene DJ, Montagnese S. (2014) 'Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy.'. Neurochem Res, United States: 40 (2), pp. 284-292.

    Abstract

    Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non-pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 ± 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 ± 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 ± 138 min) and a reduced sleep efficiency (69 ± 21%). These features were confirmed by actigraphy (sleep efficiency: 71 ± 13%; fragmentation index: 55 ± 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 ± 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline.

  • Davies SK, Ang JE, Revell VL, Holmes B, Mann A, Robertson FP, Cui N, Middleton B, Ackermann K, Kayser M, Thumser AE, Raynaud FI, Skene DJ. (2014) 'Effect of sleep deprivation on the human metabolome'. NATL ACAD SCIENCES PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111 (29), pp. 10761-10766.
  • Lech K, Ackermann K, Wollstein A, Revell VL, Skene DJ, Kayser M. (2014) 'Assessing the suitability of miRNA-142-5p and miRNA-541 for bloodstain deposition timing.'. Forensic Sci Int Genet, Netherlands: 12, pp. 181-184.

    Abstract

    A recent proof-of-concept pilot study proposed using microRNA (miRNA) markers for time of death determination. The markers - miRNA-142-5p and miRNA-541, were reported to show considerable expression differences in vitreous humor between individuals who died during the day or night. Here, we investigated whether these miRNA markers show the same diurnal expression pattern in blood, which would make them useful for estimating bloodstain deposition time to allow molecular alibi testing for forensic casework. We analyzed venous blood samples collected from 12 healthy individuals every 4h during the 24hday/night period under controlled sleep-laboratory conditions. MiRNA-142-5p normalized against miRNA-222 showed no statistically significant expression differences between blood samples collected during daytime and nighttime (one-way ANOVA p=0.81), and also no statistically significant rhythmicity during the 24hday/night period (cosine fit for all individuals p>0.05, averaged data p=0.932). MicroRNA-541 amplification in blood was above the 34-cycle threshold applied in the study, indicating too low quantities for obtaining reliable data. Overall, we conclude that the two miRNA markers previously suggested for time of death determination in vitreous humor are not suitable for estimating the deposition time of forensic bloodstains. Future studies may find out if miRNA markers with significant diurnal expression patterns can be identified and how useful they would be for forensic trace deposition timing.

  • Flynn-Evans EE, Tabandeh H, Skene DJ, Lockley SW. (2014) 'Circadian Rhythm Disorders and Melatonin Production in 127 Blind Women with and without Light Perception.'. J Biol Rhythms, 29 (3), pp. 215-224.
  • Papantoniou K, Pozo OJ, Espinosa A, Marcos J, Castaño-Vinyals G, Basagaña X, Ribas FC, Mirabent J, Martín J, Carenys G, Martín CR, Middleton B, Skene DJ, Kogevinas M. (2014) 'Circadian variation of melatonin, light exposure, and diurnal preference in day and night shift workers of both sexes.'. Cancer Epidemiol Biomarkers Prev, United States: 23 (7), pp. 1176-1186.

    Abstract

    BACKGROUND: Light-at-night has been shown in experimental studies to disrupt melatonin production but this has only partly been confirmed in studies of night shift workers. In this cross-sectional study, we examined the circadian variation of melatonin in relation to shift status, individual levels of light-at-night exposure, and diurnal preference, an attribute reflecting personal preference for activity in the morning or evening. METHODS: One hundred and seventeen workers (75 night and 42 day) of both sexes, ages 22 to 64 years, were recruited from four companies. Participants collected urine samples from all voids over 24 hours and wore a data logger continuously recording their light exposure. Sociodemographic, occupational, lifestyle, and diurnal preference information were collected by interview. Concentrations of urinary 6-sulfatoxymelatonin (aMT6s), the main melatonin metabolite, were measured. RESULTS: Mean aMT6s levels were lower in night [10.9 ng/mg creatinine/hour; 95% confidence interval (CI), 9.5-12.6] compared with day workers (15.4; 95% CI, 12.3-19.3). The lowest aMT6s levels were observed in night workers with morning preference (6.4; 95% CI, 3.0-13.6). Peak time of aMT6s production occurred 3 hours later in night (08:42 hour, 95% CI, 07:48-09:42) compared with day workers (05:36 hour, 95% CI, 05:06-06:12). Phase delay was stronger among subjects with higher light-at-night exposure and number of nights worked. CONCLUSIONS: Night shift workers had lower levels and a delay in peak time of aMT6s production over a 24-hour period. Differences were modified by diurnal preference and intensity of light-at-night exposure. IMPACT: Night shift work affects levels and timing of melatonin production and both parameters may relate to future cancer risk.

  • Papagiannidou E, Skene DJ, Ioannides C. (2014) 'Potential drug interactions with melatonin.'. Physiol Behav, United States: 131, pp. 17-24.

    Abstract

    Possible interactions of melatonin with concurrently administered drugs were investigated in in vitro studies utilising human hepatic post-mitochondrial preparations; similar studies were conducted with rat preparations to ascertain whether rat is a suitable surrogate for human. Drugs were selected based not only on the knowledge that the 6-hydroxylation of exogenous melatonin, its principal pathway of metabolism, is mainly mediated by hepatic CYP1A2, but also on the likelihood of the drug being concurrently administered with melatonin. Hepatic preparations were incubated with either melatonin or 6-hydroxymelatonin in the presence and absence of a range of concentrations of interacting drug, and the production of 6-sulphatoxymelatonin monitored using a radioimmunoassay procedure. Of the drugs screened, only the potent CYP1A2 inhibitor 5-methoxypsoralen impaired the 6-melatonin hydroxylation at pharmacologically relevant concentrations, and is likely to lead to clinical interactions; diazepam, tamoxifen and acetaminophen (paracetamol) did not impair the metabolic conversion of melatonin to 6-sulphatoxymelatonin at concentrations attained following therapeutic administration. 17-Ethinhyloestradiol appeared not to suppress the 6-hydroxylation of melatonin but inhibited the sulphation of 6-hydroxymelatonin, but this is unlikely to result in an interaction following therapeutic intake of the steroid. Species differences in the inhibition of melatonin metabolism in human and rat hepatic post-mitochondrial preparations were evident implying that the rat may not be an appropriate surrogate of human in such studies.

  • Darling AL, Hart KH, Gibbs MA, Lanham-New SA, Gossiel F, Eastell R, Kantermann T, Horton K, Johnsen S, Berry JL, Skene DJ, Vieth R. (2014) 'Greater seasonal cycling of 25-hydroxyvitamin D is associated with increased parathyroid hormone and bone resorption'. Osteoporosis International, 25 (3), pp. 933-941.

    Abstract

    This analysis assessed whether seasonal change in 25-hydroxyvitamin D concentration was associated with bone resorption, as evidenced by serum parathyroid hormone and C-terminal telopeptide concentrations. The main finding was that increased seasonal fluctuation in 25-hydroxyvitamin D was associated with increased levels of parathyroid hormone and C-terminal telopeptide. Introduction: It is established that adequate 25-hydroxyvitamin D (25(OH)D, vitamin D) concentration is required for healthy bone mineralisation. It is unknown whether seasonal fluctuations in 25(OH)D also impact on bone health. If large seasonal fluctuations in 25(OH)D were associated with increased bone resorption, this would suggest a detriment to bone health. Therefore, this analysis assessed whether there is an association between seasonal variation in 25(OH)D and bone resorption. Methods: The participants were (n = 279) Caucasian and (n = 88) South Asian women (mean (±SD); age 48.2 years (14.4)) who participated in the longitudinal Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England study (2006-2007). The main outcomes were serum 25(OH)D, serum parathyroid hormone (sPTH) and serum C-terminal telopeptide of collagen (sCTX), sampled once per season for each participant. Results: Non-linear mixed modelling showed the (amplitude/mesor) ratio for seasonal change in log 25(OH)D to be predictive of log sPTH (estimate = 0.057, 95 % CI (0.051, 0.063), p < 0.0001). Therefore, individuals with a higher seasonal change in log 25(OH)D, adjusted for overall log 25(OH)D concentration, showed increased levels of log sPTH. There was a corresponding significant ability to predict the range of seasonal change in log 25(OH)D through the level of sCTX. Here, the corresponding parameter statistics were estimate = 0.528, 95 % CI (0.418, 0.638) and p ≤ 0.0001. Conclusions: These findings suggest a possible detriment to bone health via increased levels of sPTH and sCTX in individuals with a larger seasonal change in 25(OH)D concentration. Further larger cohort studies are required to further investigate these preliminary findings. © 2013 International Osteoporosis Foundation and National Osteoporosis Foundation.

  • Montagnese S, De Rui M, Corrias M, Turco M, Merkel C, Amodio P, Gatta A, De Pittà C, Costa R, Skene DJ. (2014) 'Sleep-wake abnormalities in patients with cirrhosis'. Hepatology, 59 (2), pp. 705-712.

    Abstract

    A considerable proportion of patients with cirrhosis exhibit insomnia, delayed sleep habits, and excessive daytime sleepiness. These have been variously attributed to hepatic encephalopathy and impaired hepatic melatonin metabolism, but the understanding of their pathophysiology remains limited and their treatment problematic. Sleep is regulated by the interaction of a homeostatic and a circadian process. The homeostatic process determines sleep propensity in relation to sleep-wake history, thus the need to sleep increases with the duration of the waking period. The circadian process, which is marked by the 24-hour rhythm of the hormone melatonin, is responsible for the alternation of high/low sleep propensity in relation to dark/light cues. Circadian sleep regulation has been studied in some depth in patients with cirrhosis, who show delays in the 24-hour melatonin rhythm, most likely in relation to reduced sensitivity to light cues. However, while melatonin abnormalities are associated with delayed sleep habits, they do not seem to offer a comprehensive explanation to the insomnia exhibited by these patients. Fewer data are available on homeostatic sleep control: it has been recently hypothesized that patients with cirrhosis and hepatic encephalopathy might be unable, due to excessive daytime sleepiness, to accumulate the need/ability to produce restorative sleep. This review will describe in some detail the features of sleep-wake disturbances in patients with cirrhosis, their mutual relationships, and those, if any, with hepatic failure/hepatic encephalopathy. A separate section will cover the available information on their pathophysiology. Finally, etiological treatment will be briefly discussed. © 2013 by the American Association for the Study of Liver Diseases.

  • De Rui M, Middleton B, Sticca A, Gatta A, Amodio P, Skene DJ, Montagnese S. (2014) 'Sleep and Circadian Rhythms in Hospitalized Patients with Decompensated Cirrhosis: Effect of Light Therapy'. Neurochemical Research, 40 (2), pp. 284-292.
  • Lucas RJ, Brown TM, Peirson SN, Berson DM, Cooper HM, Czeisler CA, Lockley SW, Figueiro MG, Gamlin PD, O'Hagan JB, Price LLA, Provencio I, Skene DJ, Brainard GC. (2014) 'Measuring and using light in the melanopsin age'. Trends in Neurosciences, 37 (1), pp. 1-9.
  • Bonmati-Carrion MA, Middleton B, Revell V, Skene DJ, Rol MA, Madrid JA. (2013) 'Circadian phase asessment by ambulatory monitoring in humans: Correlation with dim light melatonin onset.'. Informa Healthcare Chronobiol Int,

    Abstract

    The increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and "WT increase onset" (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.

  • Ackermann K, Plomp R, Lao O, Middleton B, Revell VL, Skene DJ, Kayser M. (2013) 'Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans.'. Informa Healthcare Chronobiol Int, England: 30 (7), pp. 901-909.

    Abstract

    This study investigated the impact of sleep deprivation on the human circadian system. Plasma melatonin and cortisol levels and leukocyte expression levels of 12 genes were examined over 48 h (sleep vs. no-sleep nights) in 12 young males (mean ± SD: 23 ± 5 yrs). During one night of total sleep deprivation, BMAL1 expression was suppressed, the heat shock gene HSPA1B expression was induced, and the amplitude of the melatonin rhythm increased, whereas other high-amplitude clock gene rhythms (e.g., PER1-3, REV-ERBα) remained unaffected. These data suggest that the core clock mechanism in peripheral oscillators is compromised during acute sleep deprivation.

  • Kantermann T, Skene DJ, Haubruge D. (2013) 'The Shift-Work Accident Rate is More Related to the Shift Type than to Shift Rotation'. Taylor and Francis Human and Ecological Risk Assessment, 19 (6), pp. 1586-1594.

    Abstract

    The current study investigated the accident rates across morning, late, and night shifts in rotating shift-workers employed in two different shift rotations at the same steel work factory. A retrospective analysis has been performed of accident data (N = 578) over a 5-year period (2003 through 2007) of 730 male shift-workers employed in either a clockwise (mean age of the workers 38.1 ± SD 9.8 years) or counterclockwise rotation (mean age 38.0 ± SD 10.1 years) with comparable work conditions. The overall accident rate across the 24-h day was not significantly different between clockwise and counterclockwise shift rotation. In both shift-work rotations, morning shifts as opposed to night shifts exhibited a significantly higher accident rate. There was no significant difference between late shifts and morning or night shifts in either shift rotation. The increased accident rate in the morning shift at this steel factory could be related to the early starting time of the shift and to this shift being more labor intensive in both shift rotations. These findings suggest that work-related factors must be considered in addition to shift-work schedules when investigating accident rates in rotating shift-workers. © 2013 Copyright Taylor and Francis Group, LLC.

  • Lowson E, Middleton B, Arber S, Skene DJ. (2013) 'Effects of night work on sleep, cortisol and mood of female nurses, their husbands and children'. Wiley-Blackwell Sleep and Biological Rhythms, 11 (1), pp. 7-13.
  • Kantermann T, Duboutay F, Haubruge D, Kerkhofs M, Schmidt-Trucksäss A, Skene DJ. (2013) 'Atherosclerotic risk and social jetlag in rotating shift-workers: First evidence from a pilot study.'. IOS Press Work,

    Abstract

    OBJECTIVE: The aim of this study was to identify atherosclerotic risk using pulse wave velocity (PWV) in steel workers employed in different shift-work rotations, and to elucidate its relationship to social jetlag and shift schedule details. PARTICIPANTS: Male workers in a steel factory (n=77, 32 fast clockwise (CW), 30 slow counterclockwise (CC), 15 day workers (DW); mean age 42 ± SD 7.6 yrs) with at least 5 years of experience in their current work schedule participated. METHODS: All workers completed questionnaires on demographics, health, psychotropic agents, sleep, social and work life, social jetlag (difference between mid-sleep time on workdays and days off used as a marker of circadian disruption) and chronotype (mid-sleep time on free days corrected for sleep deficit on workdays). In 63 workers we measured PWV, blood pressure (BP), heart rate (HR) between 08:00 and 12:30 h in controlled posture conditions (no caffeine/smoking/exercise). RESULTS: There was no significant difference in PWV (covariates: age, BP) between the different shift-rotations (CW, CC and DW). In all workers combined, HR and social jetlag were significantly positively correlated. Demographic variables did not differ between shift-workers and day workers; shift-workers (CW, CC) reported significantly more stomach upsets, digestion problems, weight fluctuations, and social jetlag. The CW and CC workers did not differ in ratings of how shift-work affected sleep, social and work life. CONCLUSIONS: PWV was not different between the two shift-rotations. This pilot study shows first evidence that HR is related to social jetlag, and therefore warrants more studies in different shift schedules.

  • Penzel T, Pevernagie D, Dogas Z, Grote L, de Lacy S, Rodenbeck A, Bassetti C, Berg S, Cirignotta F, d'Ortho M-P, Garcia-Borreguero D, Levy P, Nobili L, Paiva T, Peigneux P, Pollmächer T, Riemann D, Skene DJ, Zucconi M, Espie C. (2013) 'Catalogue of knowledge and skills for sleep medicine'. Wiley Journal of Sleep Research,
  • Ang JE, Revell V, Mann A, Mäntele S, Otway DT, Johnston JD, Thumser AE, Skene DJ, Raynaud F. (2012) 'Identification of Human Plasma Metabolites Exhibiting Time-of-Day Variation Using an Untargeted Liquid Chromatography-Mass Spectrometry Metabolomic Approach.'. Informa Healthcare Chronobiol Int, England: 29 (7), pp. 868-881.

    Abstract

    Although daily rhythms regulate multiple aspects of human physiology, rhythmic control of the metabolome remains poorly understood. The primary objective of this proof-of-concept study was identification of metabolites in human plasma that exhibit significant 24-h variation. This was assessed via an untargeted metabolomic approach using liquid chromatography-mass spectrometry (LC-MS). Eight lean, healthy, and unmedicated men, mean age 53.6 (SD ± 6.0) yrs, maintained a fixed sleep/wake schedule and dietary regime for 1 wk at home prior to an adaptation night and followed by a 25-h experimental session in the laboratory where the light/dark cycle, sleep/wake, posture, and calorific intake were strictly controlled. Plasma samples from each individual at selected time points were prepared using liquid-phase extraction followed by reverse-phase LC coupled to quadrupole time-of-flight MS analysis in positive ionization mode. Time-of-day variation in the metabolites was screened for using orthogonal partial least square discrimination between selected time points of 10:00 vs. 22:00 h, 16:00 vs. 04:00 h, and 07:00 (d 1) vs. 16:00 h, as well as repeated-measures analysis of variance with time as an independent variable. Subsequently, cosinor analysis was performed on all the sampled time points across the 24-h day to assess for significant daily variation. In this study, analytical variability, assessed using known internal standards, was low with coefficients of variation <10%. A total of 1069 metabolite features were detected and 203 (19%) showed significant time-of-day variation. Of these, 34 metabolites were identified using a combination of accurate mass, tandem MS, and online database searches. These metabolites include corticosteroids, bilirubin, amino acids, acylcarnitines, and phospholipids; of note, the magnitude of the 24-h variation of these identified metabolites was large, with the mean ratio of oscillation range over MESOR (24-h time series mean) of 65% (95% confidence interval [CI]: 49-81%). Importantly, several of these human plasma metabolites, including specific acylcarnitines and phospholipids, were hitherto not known to be 24-h variant. These findings represent an important baseline and will be useful in guiding the design and interpretation of future metabolite-based studies. (Author correspondence: Jooern.Ang@icr.ac.uk or Florence.Raynaud@icr.ac.uk ).

  • Fischer J, Dogas Z, Bassetti CL, Berg S, Grote L, Jennum P, Levy P, Mihaicuta S, Nobili L, Riemann D, Puertas Cuesta FJ, Skene DJ, Stanley N, Pevernagie D, Raschke F. (2012) 'Standard procedures for adults in accredited sleep medicine centres in Europe'. Journal of Sleep Research, 21 (4), pp. 357-368.
  • Ackermann K, Revell VL, Lao O, Rombouts EJ, Skene DJ, Kayser M. (2012) 'Diurnal rhythms in blood cell populations and the effect of acute sleep deprivation in healthy young men.'. Sleep, United States: 35 (7), pp. 933-940.

    Abstract

    The sleep/wake cycle is accompanied by changes in circulating numbers of immune cells. The goal of this study was to provide an in-depth characterization of diurnal rhythms in different blood cell populations and to investigate the effect of acute sleep deprivation on the immune system, as an indicator of the body's acute stress response.

  • Wehrens SMT, Hampton SM, Kerkhofs M, Skene DJ. (2012) 'Mood, Alertness, and Performance in Response to Sleep Deprivation and Recovery Sleep in Experienced Shiftworkers Versus Non-Shiftworkers'. Informa Clin Med Chronobiology International, 29 (5), pp. 537-548.
  • Wehrens SM, Hampton SM, Skene DJ. (2012) 'Heart rate variability and endothelial function after sleep deprivation and recovery sleep among male shift and non-shift workers.'. Scandinavian Journal of Work, Environmental & Health Scandinavian Journal of Work, Environmental & Health, 38 (12), pp. 171-181.

    Abstract

    OBJECTIVES: Endothelial dysfunction and alterations in heart rate variability (HRV) as well as sleep deprivation and shift work have been associated with cardiovascular disease. The aim of this study was to compare HRV and endothelial function among shift and matched non-shift workers in response to total sleep deprivation and recovery sleep under identical laboratory settings. METHODS: Eleven experienced male shift workers (shift work ≥5 years) and 14 non-shift workers were matched for age, body mass index, and cholesterol. HRV parameters [eg, HR variance and low frequency/high frequency (LF/HF) ratio] were derived from 5-minute electrocardiogram bins at 0.25, 4.25, 11.5, 12.5, and 13.5 hours after habitual wake-up time and endothelial function was assessed by flow-mediated dilatation (FMD) using ultrasound at 0.75 and 10.75 hours after habitual wake-up time, following baseline sleep, total sleep deprivation, and recovery sleep (posture- and food-controlled throughout). Circadian phase was assessed before baseline sleep by salivary dim light melatonin onset. RESULTS: There was no difference in circadian phase between shift and non-shift workers. HR variance was highest at 0.25 hours following total sleep deprivation and lowest after recovery sleep. A significantly higher LF/HF ratio, significantly lower HR variance, and a trend for a lower %FMD (P=0.08) were observed among shift compared to non-shift workers. CONCLUSION: Despite similar demographics, circadian phase, posture and food intake, differences in endothelial function and HRV were observed in the two groups, which may reflect higher sympathetic and/or lower parasympathetic activity, contributing to increased cardiovascular risk among the shift workers.

  • Papamichael C, Skene DJ, Revell VL. (2012) 'Human non-visual responses to simultaneous presentation of blue and red monochromatic light.'. Sage Journal of Biological Rhythms, 27 (1), pp. 70-78.

    Abstract

    Blue light sensitivity of melatonin suppression and subjective mood and alertness responses in humans is recognised as being melanopsin based. Observations that long wavelength (red) light can potentiate responses to subsequent short wavelength (blue) light have been attributed to the bistable nature of melanopsin whereby it forms stable associations with both 11-cis and alltrans isoforms of retinaldehyde and uses light to transition between these states. The current study examined the effect of concurrent administration of blue and red monochromatic light, as would occur in real-world white light, on acute melatonin suppression and subjective mood and alertness responses in humans. Young healthy males (18-35 years; n = 21) were studied in highly controlled laboratory sessions that included an individually timed 30 min light stimulus of blue (λmax 479 nm) or red (λmax 627 nm) monochromatic light at varying intensities (1013 - 1014 photons/cm2/s) presented, either alone or in combination, in a within-subject randomised design. Plasma melatonin levels and subjective mood and alertness were assessed at regular intervals relative to the light stimulus. Subjective alertness levels were elevated after light onset irrespective of light wavelength or irradiance. For melatonin suppression, a significant irradiance response was observed with blue light. Co-administration of red light, at any of the irradiances tested, did not significantly alter the response to blue light alone. Under the current experimental conditions the primary determinant of the melatonin suppression response was the irradiance of blue 479 nm light and this was unaffected by simultaneous red light administration.

  • Kantermann T, Wehrens SM, Ulhôa MA, Moreno C, Skene DJ. (2012) 'Noisy and individual, but doable: shift-work research in humans.'. Elsevier Prog Brain Res, Netherlands: 199, pp. 399-411.

    Abstract

    Working around the clock is common for many occupations, as diverse as nurses, truck drivers, physicians, steel workers, and pilots. Each shift-work profession is individual in more aspects than just work hours and individual work scenarios, each posing a different impact on the health of workers. Related health problems in shift workers, therefore, are also diverse and encompass sleep problems, metabolic and cardiovascular system disturbances, as well as cancer. Little is known about how all these individual factors influence a shift worker's health status, partly because many shift-work studies show inconsistent results. In addition, these individual factors create many methodological difficulties for researchers who investigate such work scenarios. This chapter presents examples from our laboratory and field studies of shift workers, which emphasize the importance of taking individual circumstances into account. Both study approaches, laboratory and field based, are needed to fully account for the difficulties that shift-work studies pose on both workers and researchers. Finally, understanding the mechanisms that underpin interindividual differences in response to shift work will advance our understanding of how to design better and healthier shift-work schedules in the future.

  • Mäntele S, Otway DT, Middleton B, Bretschneider S, Wright J, Robertson MD, Skene DJ, Johnston JD. (2012) 'Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men.'. Public Library of Science PLoS One, United States: 7 (5)

    Abstract

    Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45-65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001) effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual's 24-hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05) of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin relative to cycle mean, or expression of subcutaneous adipose leptin gene expression, compared with lean subjects.

  • Ackermann K, Revell VL, Lao O, Rombouts EJ, Skene DJ, Kayser M. (2012) 'Diurnal Rhythms in Blood Cell Populations and the Effect of Acute Sleep Deprivation in Healthy Young Men'. SLEEP, 35 (7), pp. 933-940.
  • De Rui M, Gaiani S, Middleton B, Skene DJ, Schiff S, Gatta A, Merkel C, Amodio P, Montagnese S. (2011) 'Bright times for patients with cirrhosis and delayed sleep habits: a case report on the beneficial effect of light therapy.'. Am J Gastroenterol, United States: 106 (11), pp. 2048-2049.
  • Ulhôa MA, Marqueze EC, Kantermann T, Skene D, Moreno C. (2011) 'When does stress end? Evidence of a prolonged stress reaction in shiftworking truck drivers.'. Informa Healthcare Chronobiology International, England: 28 (9), pp. 810-818.

    Abstract

    This study aimed to analyze individual cortisol levels in relation to work conditions, sleep, and health parameters among truck drivers working day shifts (n?=?21) compared to those working irregular shifts (n?=?21). A total of 42 male truck drivers (39.8???6.2 yrs) completed questionnaires about sociodemographics, job content, work environment, health, and lifestyle. Rest-activity profiles were measured using actigraphy, and cardiovascular blood parameters were collected. Salivary cortisol samples were obtained: (i) at waking time, (ii) 30?min after waking, and (iii) at bedtime, during both one workday and one day off from work. Irregular-shift workers, compared to day-shift workers, showed significantly higher waist-hip ratio, very-low-density lipoprotein (VLDL) cholesterol, tiredness after work, years working as a driver, truck vibration, and less job demand (p?

  • Schmoll C, Lascaratos G, Dhillon B, Skene D, Riha RL. (2011) 'The role of retinal regulation of sleep in health and disease'. W B SAUNDERS CO LTD SLEEP MEDICINE REVIEWS, 15 (2), pp. 107-113.
  • Otway DT, Mäntele S, Bretschneider S, Wright J, Trayhurn P, Skene DJ, Robertson MD, Johnston JD. (2011) 'Rhythmic Diurnal Gene Expression in Human Adipose Tissue From Individuals Who Are Lean, Overweight, and Have Type 2 Diabetes.'. Diabetes,
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2011) 'Changes in the 24-h plasma cortisol rhythm in patients with cirrhosis'. ELSEVIER SCIENCE BV JOURNAL OF HEPATOLOGY, 54 (3), pp. 588-590.
  • Revell VL, Barrett DCG, Schlangen LJM, Skene DJ. (2010) 'PREDICTING HUMAN NOCTURNAL NONVISUAL RESPONSES TO MONOCHROMATIC AND POLYCHROMATIC LIGHT WITH A MELANOPSIN PHOTOSENSITIVITY FUNCTION'. INFORMA HEALTHCARE CHRONOBIOLOGY INTERNATIONAL, 27 (9-10), pp. 1762-1777.
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2010) 'On the Origin and the Consequences of Circadian Abnormalities in Patients With Cirrhosis'. NATURE PUBLISHING GROUP AMERICAN JOURNAL OF GASTROENTEROLOGY, 105 (8), pp. 1773-1781.
  • Wehrens SMT, Hampton SM, Finn RE, Skene DJ. (2010) 'Effect of total sleep deprivation on postprandial metabolic and insulin responses in shift workers and non-shift workers'. BIOSCIENTIFICA LTD JOURNAL OF ENDOCRINOLOGY, 206 (2), pp. 205-215.
  • Thorne HC, Hampton SM, Morgan LM, Skene DJ, Arendt J. (2010) 'Returning from night shift to day life: Beneficial effects of light on sleep'. WILEY-BLACKWELL SLEEP AND BIOLOGICAL RHYTHMS, 8 (3), pp. 212-221.
  • Archer SN, Carpen JD, Gibson M, Lim GH, Johnston JD, Skene DJ, von Schantz M. (2010) 'Polymorphism in the PER3 Promoter Associates with Diurnal Preference and Delayed Sleep Phase Disorder'. AMER ACAD SLEEP MEDICINE SLEEP, 33 (5), pp. 695-701.

    Abstract

    Study Objectives: To screen the PER3 promoter for polymorphisms and investigate the phenotypic associations of these polymorphisms with diurnal preference, delayed sleep phase disorder/syndrome (DSPD/DSPS), and their effects on reporter gene expression. Design: Interspecific comparison was used to define the approximate extent of the PER3 promoter as the region between the transcriptional start site and nucleotide position −874. This region was screened in DNA pools using PCR and direct sequencing, which was also used to screen DNA from individual participants. The different promoter alleles were cloned into a luciferase expression vector and a deletion library created. Promoter activation was measured by chemiluminescence. Setting: N/A Patients or Participants: DNA samples were obtained from volunteers with defined diurnal preference (3 x 80, selected from a pool of 1,590), and DSPD patients (n = 23). Interventions: N/A Measurements and Results: We verified three single nucleotide polymorphisms (G −320T, C −319A, G −294A), and found a novel variable number tandem repeat (VNTR) polymorphism (−318 1/2 VNTR). The −320T and −319A alleles occurred more frequently in DSPD compared to morning (P = 0.042 for each) or evening types (P = 0.006 and 0.033). The allele combination TA2G was more prevalent in DSPD compared to morning (P = 0.033) or evening types (P = 0.002). Luciferase expression driven by the TA2G combination was greater than for the more common GC2A (P < 0.05) and the rarer TA1G (P < 0.001) combinations. Deletion reporter constructs identified two enhancer regions (−703 to −605, and −283 to −80). Conclusions: Polymorphisms in the PER3 promoter could affect its expression, leading to potential differences in the observed functions of PER3.

  • Revell VL, Skene DJ. (2010) 'Impact of age on human non-visual responses to light'. WILEY-BLACKWELL SLEEP AND BIOLOGICAL RHYTHMS, 8 (2), pp. 84-94.
  • Pagani L, Semenova EA, Moriggi E, Revell VL, Hack LM, Lockley SW, Arendt J, Skene DJ, Meier F, Izakovic J. (2010) 'The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.'. Public Library of Science PLoS One, United States: 5 (10)

    Abstract

    Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior.

  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2010) 'Melatonin Rhythms in Patients With Cirrhosis'. NATURE PUBLISHING GROUP AMERICAN JOURNAL OF GASTROENTEROLOGY, 105 (1), pp. 220-222.
  • Jud C, Chappuis S, Revell VL, Sletten TL, Saaltink D-J, Cajochen C, Skene DJ, Albrecht U. (2009) 'AGE-DEPENDENT ALTERATIONS IN HUMAN PER2 LEVELS AFTER EARLY MORNING BLUE LIGHT EXPOSURE'. INFORMA HEALTHCARE CHRONOBIOLOGY INTERNATIONAL, 26 (7), pp. 1462-1469.
  • Montagnese S, Middleton B, Skene DJ, Morgan MY. (2009) 'Sleep-wake patterns in patients with cirrhosis: All you need to know on a single sheet A simple sleep questionnaire for clinical use'. ELSEVIER SCIENCE BV JOURNAL OF HEPATOLOGY, 51 (4), pp. 690-695.
  • Montagnese S, Middleton B, Skene DJ, Morgan MY. (2009) 'Night-time sleep disturbance does not correlate with neuropsychiatric impairment in patients with cirrhosis'. WILEY-BLACKWELL PUBLISHING, INC LIVER INTERNATIONAL, 29 (9), pp. 1372-1382.
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2009) 'Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome?'. SPRINGER/PLENUM PUBLISHERS METABOLIC BRAIN DISEASE, 24 (3), pp. 427-439.
  • Staples VSL, Archer SN, Arber S, Skene DJ. (2009) 'Daily light exposure profiles in older non-resident extreme morning and evening types'. WILEY-BLACKWELL PUBLISHING, INC JOURNAL OF SLEEP RESEARCH, 18 (4), pp. 466-471.
  • Zawilska JB, Skene DJ, Arendt J. (2009) 'Physiology and pharmacology of melatonin in relation to biological rhythms'. POLISH ACAD SCIENCES INST PHARMACOLOGY PHARMACOLOGICAL REPORTS, 61 (3), pp. 383-410.
  • Gogenur I, Kucukakin B, Bisgaard T, Kristiansen V, Hjorto N-C, Skene DJ, Rosenberg J. (2009) 'The Effect of Melatonin on Sleep Quality After Laparoscopic Cholecystectomy: A Randomized, Placebo-Controlled Trial'. LIPPINCOTT WILLIAMS & WILKINS ANESTHESIA AND ANALGESIA, 108 (4), pp. 1152-1156.
  • Sletten TL, Revell VL, Middleton B, Lederle KA, Skene DJ. (2009) 'Age-Related Changes in Acute and Phase-Advancing Responses to Monochromatic Light'. SAGE PUBLICATIONS INC JOURNAL OF BIOLOGICAL RHYTHMS, 24 (1), pp. 73-84.
  • Ackermann K, Sletten TL, Revell VL, Archer SN, Skene DJ. (2009) 'Blue-Light Phase Shifts PER3 Gene Expression in Human Leukocytes'. TAYLOR & FRANCIS INC CHRONOBIOLOGY INTERNATIONAL, 26 (4) Article number PII 911212256 , pp. 769-779.
  • Dawson J, Boyle J, Stanley N, Johnsen S, Hindrnarch I, Skene DJ. (2008) 'Benzodiazepine-induced reduction in activity mirrors decrements in cognitive and psychomotor performance'. JOHN WILEY & SONS LTD HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL, 23 (7), pp. 605-613.
  • Arendt J, Van Someren EJW, Appleton R, Skene DJ, Akerstedt T. (2008) 'Clinical update: melatonin and sleep disorders'. ROY COLL PHYS LONDON EDITORIAL OFFICE CLINICAL MEDICINE, 8 (4), pp. 381-383.
  • Lockley SW, Dijk D-J, Kosti O, Skene DJ, Arendt J. (2008) 'Alertness, mood and performance rhythm disturbances associated with circadian sleep disorders in the blind'. WILEY-BLACKWELL JOURNAL OF SLEEP RESEARCH, 17 (2), pp. 207-216.
  • Thorne H, Hampton S, Morgan L, Skene DJ, Arendt J. (2008) 'Differences in sleep, light, and circadian phase in offshore 18.00-06.00 h and 19.00-07.00 h shift workers'. INFORMA HEALTHCARE CHRONOBIOLOGY INTERNATIONAL, Yeppoon, AUSTRALIA: 25 (2-3), pp. 225-235.
  • Skene DJ, Arendt J. (2007) 'Circadian rhythm sleep disorders in the blind and their treatment with melatonin'. ELSEVIER SCIENCE BV SLEEP MEDICINE, 8 (6), pp. 651-655.
  • Gogenur I, Middleton B, Kristiansen VB, Skene DJ, Rosenberg J. (2007) 'Disturbances in melatonin and core body temperature circadian rhythms after minimal invasive surgery'. BLACKWELL PUBLISHING ACTA ANAESTHESIOLOGICA SCANDINAVICA, 51 (8), pp. 1099-1106.
  • Gogenur I, Middleton B, Burgdorf S, Rasmussen LS, Skene DJ, Rosenberg J. (2007) 'Impact of sleep and circadian disturbances in urinary 6-sulphatoxymelatonin levels, on cognitive function after major surgery'. BLACKWELL PUBLISHING JOURNAL OF PINEAL RESEARCH, 43 (2), pp. 179-184.
  • Zawilska JB, Lorenc A, Berezinska M, Vivien-Roels B, Pevet P, Skene DJ. (2007) 'Photoperiod-dependent changes in melatonin synthesis in the turkey pineal gland and retina'. POULTRY SCIENCE ASSOC INC POULTRY SCIENCE, 86 (7), pp. 1397-1405.
  • Viola AU, Archer SN, James LM, Groeger JA, Lo JCY, Skene DJ, von Schantz M, Dijk D-J. (2007) 'PER3 polymorphism predicts sleep structure and waking performance'. CELL PRESS CURRENT BIOLOGY, 17 (7), pp. 613-618.
  • Jones KHS, Ellis J, Von Schantz M, Skene DJ, Dijk D-J, Archer SN. (2007) 'Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities'. BLACKWELL PUBLISHING JOURNAL OF SLEEP RESEARCH, 16 (1), pp. 12-16.
  • Gogenur I, Ocak U, Altunpinar O, Middleton B, Skene DJ, Rosenberg J. (2007) 'Disturbances in melatonin, cortisol and core body temperature rhythms after major surgery'. SPRINGER WORLD JOURNAL OF SURGERY, 31 (2), pp. 290-298.
  • Lockley SW, Arendt J, Skene DJ. (2007) 'Visual impairment and circadian rhythm disorders.'. Dialogues Clin Neurosci, France: 9 (3), pp. 301-314.

    Abstract

    Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal "pacemaker" in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment. Sighted individuals take this daily synchronization process for granted, although they experience some of the consequences of circadian desynchrony when "jetlagged" or working night shifts. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the hypothalamic circadian clock, resulting in cyclical episodes of poor sleep and daytime dysfunction. Daily melatonin administration, which provides a replacement synchronizing daily "time cue, " is a promising therapeutic strategy, although optimal treatment dose and timing remain to be determined.

  • Revell VL, Skene DJ. (2007) 'Light-induced melatonin suppression in humans with polychromatic and monochromatic light'. TAYLOR & FRANCIS INC CHRONOBIOLOGY INTERNATIONAL, 24 (6), pp. 1125-1137.
  • Skene DJ, Arendt J. (2006) 'Human circadian rhythms: physiological and therapeutic relevance of light and melatonin'. ROYAL SOC MEDICINE PRESS LTD ANNALS OF CLINICAL BIOCHEMISTRY, 43, pp. 344-353.
  • Skene DJ, Timbers SE, Middleton B, English J, Kopp C, Tobler I, Ioannides C. (2006) 'Mice convert melatonin to 6-sulphatoxymelatonin'. ACADEMIC PRESS INC ELSEVIER SCIENCE GENERAL AND COMPARATIVE ENDOCRINOLOGY, 147 (3), pp. 371-376.
  • Walters JF, Hampton SM, Deanfield JE, Donald AE, Skene DJ, Ferns GAA. (2006) 'Circadian variation in endothelial function is attenuated in postmenopausal women'. ELSEVIER IRELAND LTD MATURITAS, 54 (3), pp. 294-303.
  • Revell VL, Arendt J, Louis FF, Skene DJ. (2006) 'Alerting effects of light are sensitive to very short wavelengths'. ELSEVIER IRELAND LTD NEUROSCIENCE LETTERS, 399 (1-2), pp. 96-100.
  • Zawilska JB, Lorenc A, Berezinska M, Vivien-Roels B, Pevet P, Skene DJ. (2006) 'Diurnal and circadian rhythms in melatonin synthesis in the turkey pineal gland and retina'. ACADEMIC PRESS INC ELSEVIER SCIENCE GENERAL AND COMPARATIVE ENDOCRINOLOGY, 145 (2), pp. 162-168.
  • Carpen JD, von Schantz M, Smits M, Skene DJ, Archer SN. (2006) 'A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans'. SPRINGER TOKYO JOURNAL OF HUMAN GENETICS, 51 (12), pp. 1122-1125.
  • Carpen JD, Archer SN, Skene DJ, Smits M, von Schantz M. (2005) 'A single-nucleotide polymorphism in the 5 '-untranslated region of the hPER2 gene is associated with diurnal preference'. BLACKWELL PUBLISHING JOURNAL OF SLEEP RESEARCH, 14 (3), pp. 293-297.
  • Mistlberger RE, Skene DJ. (2005) 'Nonphotic entrainment in humans?'. SAGE PUBLICATIONS LTD JOURNAL OF BIOLOGICAL RHYTHMS, 20 (4), pp. 339-352.
  • Revell VL, Arendt J, Terman M, Skene DJ. (2005) 'Short-wavelength sensitivity of the human circadian system to phase-advancing light'. SAGE PUBLICATIONS LTD JOURNAL OF BIOLOGICAL RHYTHMS, 20 (3), pp. 270-272.
  • Herljevic M, Middleton B, Thapan K, Skene DJ. (2005) 'Light-induced melatonin suppression: age-related reduction in response to short wavelength light'. PERGAMON-ELSEVIER SCIENCE LTD EXPERIMENTAL GERONTOLOGY, 40 (3), pp. 237-242.
  • Zawilska JB, Berezinska M, Stasikowska O, Lorenc A, Skene DJ, Nowak JZ. (2005) 'Posthatching developmental changes in noradrenaline content in the chicken pineal gland'. BLACKWELL MUNKSGAARD JOURNAL OF PINEAL RESEARCH, 38 (2), pp. 123-129.
  • Arendt J, Skene DJ. (2005) 'Melatonin as a chronobiotic'. W B SAUNDERS CO LTD SLEEP MEDICINE REVIEWS, 9 (1), pp. 25-39.
  • Dzaja A, Arber S, Hislop J, Kerkhofs M, Kopp C, Pollmacher T, Polo-Kantola P, Skene DJ, Stenuit P, Tobler I, Porkka-Heiskanen T. (2005) 'Women's sleep in health and disease'. PERGAMON-ELSEVIER SCIENCE LTD JOURNAL OF PSYCHIATRIC RESEARCH, 39 (1), pp. 55-76.
  • Walters JF, Hampton SM, Ferns GAA, Skene DJ. (2005) 'Effect of menopause on melatonin and alertness rhythms investigated in constant routine conditions'. TAYLOR & FRANCIS INC CHRONOBIOLOGY INTERNATIONAL, 22 (5), pp. 859-872.
  • Arendt J, Stone B, Skene DJ. (2005) 'Sleep Disruption in Jet Lag and Other Circadian Rhythm-Related Disorders'. , pp. 659-672.
  • Carpen JD, Archer SN, Skene DJ, Smits M, Von Schantz M. (2005) 'A single-nucleotide polymorphism in the 5′-untranslated region of the hPER2 gene is associated with diurnal preference'. Journal of Sleep Research, 14 (3), pp. 293-297.
  • Mistlberger RE, Skene DJ. (2004) 'Social influences on mammalian circadian rhythms: animal and human studies'. CAMBRIDGE UNIV PRESS BIOLOGICAL REVIEWS, 79 (3), pp. 533-556.
  • Zawilska JB, Berezinska M, Lorenc A, Skene DJ, Nowak JZ. (2004) 'Retinal illumination phase shifts the circadian rhythm of serotonin N-acetyltransferase activity in the chicken pineal gland'. ELSEVIER SCI IRELAND LTD NEUROSCIENCE LETTERS, 360 (3), pp. 153-156.
  • Zawilska JB, Berezinska M, Rosiak J, Skene DJ, Vivien-Roels B, Nowak JZ. (2004) 'Suppression of melatonin biosynthesis in the chicken pineal gland by retinally perceived light - involvement of D1-dopamine receptors'. BLACKWELL MUNKSGAARD JOURNAL OF PINEAL RESEARCH, 36 (2), pp. 80-86.
  • Zawilska JB, Berezinska M, Rosiak J, Vivien-Roels B, Skene DJ, Pevet P, Nowak JZ. (2003) 'Daily variation in the concentration of melatonin and 5-methoxytryptophol in the goose pineal gland, retina, and plasma'. ACADEMIC PRESS INC ELSEVIER SCIENCE GENERAL AND COMPARATIVE ENDOCRINOLOGY, 134 (3), pp. 296-302.
  • Hack LM, Lockley SW, Arendt J, Skene DJ. (2003) 'The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects'. SAGE PUBLICATIONS LTD JOURNAL OF BIOLOGICAL RHYTHMS, 18 (5), pp. 420-429.
  • Warman VL, Dijk DJ, Warman GR, Arendt J, Skene DJ. (2003) 'Phase advancing human circadian rhythms with short wavelength light'. ELSEVIER SCI IRELAND LTD NEUROSCIENCE LETTERS, 342 (1-2), pp. 37-40.
  • Walters JF, Skene DJ, Hampton SM, Ferns GAA. (2003) 'Biological rhythms, endothelial health and cardiovascular disease'. Medical Science Monitor, 9 (1)
  • Archer SN, Robilliard DL, Skene DJ, Smits M, Williams A, Arendt J, Von Schantz M. (2003) 'A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference'. Sleep, 26 (4), pp. 413-415.

    Abstract

    Study Objectives: To investigate the link between extreme diurnal preference, delayed sleep phase syndrome, and a length polymorphism in Per3. Design: Subjects were genotyped using polymerase chain reaction. Patients or Participants: Subjects with defined diurnal preference as determined by the Horne-Östberg questionnaire and patients with delayed sleep phase syndrome. Measurements and Results: The Per3 polymorphism correlated significantly with extreme diurnal preference, the longer allele associating with morningness and the shorter allele with eveningness. The shorter allele was strongly associated with the delayed sleep phase syndrome patients, 75% of whom were homozygous. Conclusion: The length of the Per3 repeat region identifies a potential genetic marker for extreme diurnal preference.

  • Skene DJ, Swaab DF. (2003) 'Melatonin rhythmicity: effect of age and Alzheimer's disease'. PERGAMON-ELSEVIER SCIENCE LTD EXPERIMENTAL GERONTOLOGY, BREGENZ, AUSTRIA: 38 (1-2) Article number PII S0531-5565(02)00198-5 , pp. 199-206.
  • Robilliard DL, Archer SN, Arendt J, Lockley SW, Hack LM, English J, Leger D, Smits MG, Williams A, Skene DJ, von Schantz M. (2002) 'The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects'. BLACKWELL PUBLISHING LTD JOURNAL OF SLEEP RESEARCH, 11 (4), pp. 305-312.
  • Zawilska JB, Rosiak J, Vivien-Roels B, Skene DJ, Pevet P, Nowak JZ. (2002) 'Daily variation in the concentration of 5-methoxytryptophol and melatonin in the duck pineal gland and plasma'. BLACKWELL MUNKSGAARD JOURNAL OF PINEAL RESEARCH, 32 (4), pp. 214-218.
  • Skene DJ, Papagiannidou E, Hashemi E, Snelling J, Lewis DFV, Fernandez M, Ioannides C. (2001) 'Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices'. MUNKSGAARD INT PUBL LTD JOURNAL OF PINEAL RESEARCH, 31 (4), pp. 333-342.
  • Thapan K, Arendt J, Skene DJ. (2001) 'An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans'. CAMBRIDGE UNIV PRESS J PHYSIOL-LONDON, 535 (1), pp. 261-267.
  • Zawilska JB, Rosiak J, Vivien-Roels B, Skene DJ, Pevet P, Nowak JZ. (2000) 'Effects of cycloheximide and aminophylline on 5-methoxytryptophol and melatonin contents in the chick pineal gland'. ACADEMIC PRESS INC GENERAL AND COMPARATIVE ENDOCRINOLOGY, 120 (2), pp. 212-219.
  • Zawilska JB, Vivien-Roels B, Skene DJ, Pevet P, Nowak JZ. (2000) 'Phase-shifting effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin in the chick pineal gland'. MUNKSGAARD INT PUBL LTD JOURNAL OF PINEAL RESEARCH, 29 (1), pp. 1-7.
  • Lockley SW, Skene DJ, James K, Thapan K, Wright J, Arendt J. (2000) 'Melatonin administration can entrain the free-running circadian system of blind subjects'. SOC ENDOCRINOLOGY JOURNAL OF ENDOCRINOLOGY, 164 (1), pp. R1-R6.
  • Lockley SW, Skene DJ, Arendt J. (1999) 'Comparison between subjective and actigraphic measurement of sleep and sleep rhythms'. BLACKWELL SCIENCE LTD JOURNAL OF SLEEP RESEARCH, 8 (3), pp. 175-183.
  • Arendt J, Middleton B, Stone B, Skene D. (1999) 'Complex effects of melatonin: Evidence for photoperiodic responses in humans?'. AMER SLEEP DISORDERS ASSOC SLEEP, 22 (5), pp. 625-635.
  • Lockley SW, Skene DJ, Butler LJ, Arendt J. (1999) 'Sleep and activity rhythms are related to circadian phase in the blind'. AMER ACAD SLEEP MEDICINE SLEEP, 22 (5), pp. 616-623.
  • Skene DJ, Lockley SW, James K, Arendt J. (1999) 'Correlation between urinary cortisol and 6-sulphatoxymelatonin rhythms in field studies of blind subjects'. BLACKWELL SCIENCE LTD CLINICAL ENDOCRINOLOGY, 50 (6), pp. 715-719.
  • Skene DJ, Lockley SW, Thapan K, Arendt J. (1999) 'Effects of light on human circadian rhythms'. EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER REPRODUCTION NUTRITION DEVELOPMENT, TOURS, FRANCE: 39 (3), pp. 295-304.
  • Skene DJ, Lockley SW, Arendt J. (1999) 'Melatonin in circadian sleep disorders in the blind'. KARGER BIOLOGICAL SIGNALS AND RECEPTORS, 8 (1-2), pp. 90-95.
  • Tabandeh H, Lockley SW, Buttery R, Skene DJ, Defrance R, Arendt J, Bird AC. (1998) 'Disturbance of sleep in blindness'. ELSEVIER SCIENCE INC AMERICAN JOURNAL OF OPHTHALMOLOGY, 126 (5), pp. 707-712.
  • Lockley SW, Skene DJ, Thapan K, English J, Ribeiro D, Haimov I, Hampton S, Middleton B, von Schantz M, Arendt J. (1998) 'Extraocular light exposure does not suppress plasma melatonin in humans'. ENDOCRINE SOC J CLIN ENDOCR METAB, 83 (9), pp. 3369-3372.

    Abstract

    Light affects the circadian axis in at least two ways. It can cause the acute suppression of pineal melatonin synthesis, and/or a phase-shift of the circadian oscillator. As recent evidence has suggested that extraocular light exposure may cause phase-shifts of the circadian clock, we have investigated whether suppression of melatonin can be induced by the same type of light exposure. In the first study subjects’ eyes were exposed to white light (2250 lux for 30 min) via a fibre optic cable. As expected, suppression of nighttime plasma melatonin levels (61 ± 6%) was observed. In the second study, light of the same quality but higher intensity (14,000 or 67,500 lux for 180 mins) was delivered in the same manner to the popliteal region behind the subjects’ knees, whilst shielding their eyes. No suppression of plasma melatonin levels (4 ± 7%) was detected in any of the subjects. Thus, extraocular photoreception, if it exists in mammals, does not affect the suprachiasmatic nuclei-pineal pathway.

  • Zawilska JB, Skene DJ, Nowak JZ. (1998) '5-Methoxytryptophol rhythms in the chick pineal gland: effect of environmental lighting conditions'. ELSEVIER SCI IRELAND LTD NEUROSCIENCE LETTERS, 251 (1), pp. 33-36.
  • Arendt J, Skene DJ, Middleton B, Lockley SW, Deacon S. (1997) 'Efficacy of melatonin treatment in jet lag, shift work, and blindness'. SAGE PUBLICATIONS INC JOURNAL OF BIOLOGICAL RHYTHMS, 12 (6), pp. 604-617.
  • Lockley SW, Skene DJ, Arendt J, Tabandeh H, Bird AC, Defrance R. (1997) 'Relationship between melatonin rhythms and visual loss in the blind'. ENDOCRINE SOC J CLIN ENDOCR METAB, 82 (11), pp. 3763-3770.

    Abstract

    Melatonin rhythms were assessed in 49 registered blind individuals by measurement of the urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s). Subjects had different causes of visual loss and were classified as having light perception or better (LP; n 5 19) or having no perception of light (NPL; n 5 30). Subjects collected four-hourly urine samples (eight-hourly overnight) for 48 h at weekly intervals for 3–5 weeks. The majority of LP subjects (14 of 19) had normally entrained aMT6s rhythms (mean acrophase range, 2.4–6.2 h), 4 were abnormally entrained to 24 h (mean acrophase range, 8.9–1.0 h), and 1 was unclassified. Conversely, mostNPLsubjects had abnormal rhythms (23 of 30), the incidence of which was greater in uni- and bilaterally enucleated subjects. The majority of NPL subjects (17 of 30) had free-running aMT6s rhythms (period range, 24.13– 24.79 h), 5 were abnormally entrained to 24 h (acrophase range, 7.2–20.6 h), and 1 was unclassified. Output (micrograms of aMT6s per 24 h) and amplitude (micrograms per h) of aMT6s production did not vary between LP and NPL subjects (mean 24-h output 6 SD, 12.7 6 7.5 and 9.4 6 6.4 mg aMT6s/24 h, respectively; mean amplitude 6 SD, 0.660.4 and 0.560.3 mg/h, respectively). These results indicate that a higher proportion of NPL subjects have abnormal melatonin rhythms compared to those with LP. (J Clin Endocrinol Metab 82: 3763–3770, 1997)

  • Nicholls J, Skene DJ, Hourani SMO. (1997) 'Use of a newly developed technique to isolate rat pinealocytes and study the effects of adenosine agonists on melatonin production'. WILEY-BLACKWELL JOURNAL OF PINEAL RESEARCH, 23 (3), pp. 164-168.
  • Lockley SW, Skene DJ, Tabandeh H, Bird AC, Defrance R, Arendt J. (1997) 'Relationship between napping and melatonin in the blind.'. J Biol Rhythms, UNITED STATES: 12 (1), pp. 16-25.
  • Skene DJ. (1996) 'The miracle of melatonin: Fact, fancy and future'. SOC CHEMICAL INDUSTRY CHEMISTRY & INDUSTRY, (17), pp. 637-640.
  • Ruberg FL, Skene DJ, Hanifin JP, Rollag MD, English J, Arendt J, Brainard GC. (1996) 'Melatonin regulation in humans with color vision deficiencies'. ENDOCRINE SOC JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 81 (8), pp. 2980-2985.
  • LOCKLEY S, TABANDEH H, SKENE D, BUTTERY R, BIRD A, DEFRANCE R, ARENDT J. (1995) 'DAYTIME NAPS AND MELATONIN IN BLIND PEOPLE'. LANCET LTD LANCET, 346 (8988), pp. 1491-1491.
  • JAMES K, SKENE DJ, LUCINI V, STANKOV B, ARENDT J. (1995) 'CHARACTERIZATION OF MELATONIN BINDING-SITES IN THE EYE OF THE JAPANESE-QUAIL (COTURNIX JAPONICA)'. ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS GENERAL AND COMPARATIVE ENDOCRINOLOGY, 100 (2), pp. 188-196.
  • HOFMAN MA, SKENE DJ, SWAAB DF. (1995) 'EFFECT OF PHOTOPERIOD ON THE DIURNAL MELATONIN AND 5-METHOXYTRYPTOPHOL RHYTHMS IN THE HUMAN PINEAL-GLAND'. ELSEVIER SCIENCE BV BRAIN RESEARCH, 671 (2), pp. 254-260.
  • Leone AM, Skene D. (1994) 'Melatonin concentrations in pineal organ culture are suppressed by sera from tumor-bearing mice.'. J Pineal Res, DENMARK: 17 (1), pp. 17-19.
  • MENGEAUD V, SKENE D, PEVET P, ORTONNE JP. (1994) 'NO HIGH-AFFINITY MELATONIN BINDING-SITES ARE DETECTED IN MURINE MELANOMA-CELLS AND IN NORMAL HUMAN MELANOCYTES CULTURED IN-VITRO'. RAPID SCIENCE PUBLISHERS MELANOMA RESEARCH, 4 (2), pp. 87-91.
  • SKENE DJ, BOJKOWSKI CJ, ARENDT J. (1994) 'COMPARISON OF THE EFFECTS OF ACUTE FLUVOXAMINE AND DESIPRAMINE ADMINISTRATION ON MELATONIN AND CORTISOL PRODUCTION IN HUMANS'. BLACKWELL SCIENCE LTD BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 37 (2), pp. 181-186.
  • SKENE DJ, MASSONPEVET M, PEVET P. (1993) 'SEASONAL-CHANGES IN MELATONIN BINDING-SITES IN THE PARS TUBERALIS OF MALE EUROPEAN HAMSTERS AND THE EFFECT OF TESTOSTERONE MANIPULATION'. ENDOCRINE SOC ENDOCRINOLOGY, 132 (4), pp. 1682-1686.
  • GAUER F, MASSONPEVET M, SKENE DJ, VIVIENROELS B, PEVET P. (1993) 'DAILY RHYTHMS OF MELATONIN BINDING-SITES IN THE RAT PARS TUBERALIS AND SUPRACHIASMATIC NUCLEI - EVIDENCE FOR A REGULATION OF MELATONIN RECEPTORS BY MELATONIN ITSELF'. KARGER NEUROENDOCRINOLOGY, 57 (1), pp. 120-126.
  • SKENE DJ, MASSONPEVET M, PEVET P. (1992) 'CHARACTERIZATION OF MELATONIN BINDING-SITES IN THE PARS TUBERALIS OF THE EUROPEAN HAMSTER'. BLACKWELL SCIENCE LTD JOURNAL OF NEUROENDOCRINOLOGY, 4 (2), pp. 189-192.
  • Palazidou E, Skene D, Arendt J, Everitt B, Checkley SA. (1992) 'The acute and chronic effects of (+) and (-) oxaprotiline upon melatonin secretion in normal subjects.'. Psychol Med, ENGLAND: 22 (1), pp. 61-67.
  • SKENE DJ, VIVIENROELS B, PEVET P. (1991) 'DAY AND NIGHTTIME CONCENTRATIONS OF 5-METHOXYTRYPTOPHOL AND MELATONIN IN THE RETINA AND PINEAL-GLAND FROM DIFFERENT CLASSES OF VERTEBRATES'. ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS GENERAL AND COMPARATIVE ENDOCRINOLOGY, 84 (3), pp. 405-411.
  • Tzischinsky O, Skene D, Epstein R, Lavie P. (1991) 'Circadian rhythms in 6-sulphatoxymelatonin and nocturnal sleep in blind children.'. Chronobiol Int, UNITED STATES: 8 (3), pp. 168-175.
  • SKENE DJ, VIVIENROELS B, SPARKS DL, HUNSAKER JC, PEVET P, RAVID D, SWAAB DF. (1990) 'DAILY VARIATION IN THE CONCENTRATION OF MELATONIN AND 5-METHOXYTRYPTOPHOL IN THE HUMAN PINEAL-GLAND - EFFECT OF AGE AND ALZHEIMERS-DISEASE'. ELSEVIER SCIENCE BV BRAIN RESEARCH, 528 (1), pp. 170-174.
  • SKENE DJ, VIVIENROELS B, PEVET P. (1990) '5-METHOXYTRYPTOPHOL INJECTIONS IN THE SYRIAN-HAMSTER - PLASMA AND PINEAL CONCENTRATIONS'. ELSEVIER SCI IRELAND LTD NEUROSCIENCE LETTERS, 108 (1-2), pp. 138-142.
  • SKENE DJ, BOJKOWSKI CJ, CURRIE JE, WRIGHT J, BOULTER PS, ARENDT J. (1990) '6-SULPHATOXYMELATONIN PRODUCTION IN BREAST-CANCER PATIENTS'. MUNKSGAARD INT PUBL LTD JOURNAL OF PINEAL RESEARCH, 8 (3), pp. 269-276.
  • SKENE DJ, CHURCHILL A, RAYNAUD F, PEVET P, ARENDT J. (1989) 'RADIOIMMUNOASSAY OF 5-METHOXYTRYPTOPHOL IN PLASMA'. AMER ASSOC CLINICAL CHEMISTRY CLINICAL CHEMISTRY, 35 (8), pp. 1749-1752.
  • SKENE DJ, VIVIENROELS B, PEVET P. (1989) 'PINEAL 5-METHOXYTRYPTOPHOL RHYTHMS IN THE BOX TURTLE - EFFECT OF PHOTOPERIOD AND ENVIRONMENTAL-TEMPERATURE'. ELSEVIER SCI IRELAND LTD NEUROSCIENCE LETTERS, 98 (1), pp. 69-73.
  • PEVET P, VIVIENROELS B, MASSONPEVET M, STEINLECHNER S, SKENE D, CANGUILHEM B. (1989) 'MELATONIN, SEROTONIN, 5-HYDROXYINDOLE-3-ACETIC ACID AND N-ACETYLTRANSFERASE IN THE PINEAL OF THE EUROPEAN HAMSTER (CRICETUS-CRICETUS) KEPT UNDER NATURAL ENVIRONMENTAL-CONDITIONS - LACK OF A DAY NIGHT RHYTHM IN MELATONIN FORMATION IN SPRING AND EARLY SUMMER'. MUNKSGAARD INT PUBL LTD JOURNAL OF PINEAL RESEARCH, 6 (3), pp. 233-242.
  • BOJKOWSKI CJ, ALDHOUS ME, ENGLISH J, FRANEY C, POULTON AL, SKENE DJ, ARENDT J. (1987) 'SUPPRESSION OF NOCTURNAL PLASMA MELATONIN AND 6-SULFATOXYMELATONIN BY BRIGHT AND DIM LIGHT IN MAN'. GEORG THIEME VERLAG HORMONE AND METABOLIC RESEARCH, 19 (9), pp. 437-440.
  • SKENE DJ, PEVET P, VIVIENROELS B, MASSONPEVET M, ARENDT J. (1987) 'EFFECT OF DIFFERENT PHOTOPERIODS ON CONCENTRATIONS OF 5-METHOXYTRYPTOPHOL AND MELATONIN IN THE PINEAL-GLAND OF THE SYRIAN-HAMSTER'. J ENDOCRINOLOGY LTD JOURNAL OF ENDOCRINOLOGY, 114 (2), pp. 301-309.
  • SKENE DJ, SMITH I, ARENDT J. (1986) 'RADIOIMMUNOASSAY OF PINEAL 5-METHOXYTRYPTOPHOL IN DIFFERENT SPECIES - COMPARISON WITH PINEAL MELATONIN CONTENT'. J ENDOCRINOLOGY LTD JOURNAL OF ENDOCRINOLOGY, 110 (1), pp. 177-184.
  • SKENE DJ, MODIPANE A, JOUBERT PH. (1985) 'INVESTIGATION OF POSSIBLE POLYMORPHIC DRUG OXIDATION IN BLACK SOUTH AFRICANS'. MED ASSOC S AFRICA SOUTH AFRICAN MEDICAL JOURNAL, 68 (9), pp. 653-654.
  • SKENE DJ, MODIPANE A, JOUBERT PH. (1984) 'SERUM DIGOXIN LEVELS - A COST-BENEFIT-ANALYSIS'. MED ASSOC S AFRICA SOUTH AFRICAN MEDICAL JOURNAL, 65 (1), pp. 15-15.
  • JOUBERT PH, SEBATA PDB, BAM WJ, SKENE DJ. (1984) 'HOME URINARY GLUCOSE TESTING - ITS IMPACT ON A THIRD-WORLD DIABETIC POPULATION'. MED ASSOC S AFRICA SOUTH AFRICAN MEDICAL JOURNAL, 65 (18), pp. 731-733.
  • SKENE DJ, LEONE RM, YOUNG IM, SILMAN RE. (1983) 'THE ASSESSMENT OF A PLASMA MELATONIN ASSAY USING GAS-CHROMATOGRAPHY NEGATIVE-ION CHEMICAL IONIZATION MASS-SPECTROMETRY'. JOHN WILEY & SONS LTD BIOMEDICAL MASS SPECTROMETRY, 10 (12), pp. 655-659.
  • SKENE DJ, DALI P, BAM WJ, JOUBERT PH. (1982) 'DIABETES IN A DEVELOPING COMMUNITY - EPIDEMIOLOGY AND MANAGEMENT PROBLEMS'. MED ASSOC S AFRICA SOUTH AFRICAN MEDICAL JOURNAL, 61 (13), pp. 463-464.
  • SKENE DJ, POTGIETER B. (1981) 'INVESTIGATION OF 2 ANIMAL-MODELS OF DEPRESSION'. BUREAU SCIENTIFIC PUBL SOUTH AFRICAN JOURNAL OF SCIENCE, 77 (4), pp. 180-182.

Conference papers

  • Isherwood C, Otway DT, Maentele S, Middleton B, Wright J, Robertson MD, Skene DJ, Gibbs M, Johnston JD. (2015) 'Daily rhythms in hormonal markers of diabetes and obesity: effect of weight and Type 2 diabetes'. CAMBRIDGE UNIV PRESS PROCEEDINGS OF THE NUTRITION SOCIETY, 74 (OCE1), pp. E37-E37.
  • Ang JE, Pandher R, Asad Y, Skene DJ, Workman P, Eccles S, De Bono J, Kaye S, Banerji U, Davies S, Raynaud FI. (2014) 'Plasma metabolomic signature of novel signal transduction inhibitors from preclinical identification to clinical validation'. ELSEVIER SCI LTD EUROPEAN JOURNAL OF CANCER, European Org Res & Treatment Canc, Barcelona, SPAIN: 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics 50, pp. 148-149.
  • Turco M, Caccin L, Corrias M, Biscontin A, De Pitta C, Middleton B, Skene DJ, Costa R, Montagnese S. (2014) 'Length polymorphism in the human clock gene Period3 and diurnal preference, subjective sleepiness and the response to morning light'. WILEY-BLACKWELL JOURNAL OF SLEEP RESEARCH, Tallinn, ESTONIA: 22nd Congress of the European-Sleep-Research-Society 23, pp. 55-56.
  • Skene DJ, Davies SK, Ang JE, Revell VL, Holmes B, Mann A, Robertson R, Cui N, Middleton B, Ackermann K, Kayser M, Thumser AE, Raynaud FI. (2014) 'Effect of sleep deprivation on human plasma metabolome rhythms'. WILEY-BLACKWELL JOURNAL OF SLEEP RESEARCH, Tallinn, ESTONIA: 22nd Congress of the European-Sleep-Research-Society 23, pp. 36-37.
  • Montagnese SM, De Rui M, Corrias M, Turco M, Amodio P, De Pitta C, Costa R, Middleton B, Skene DJ. (2014) 'Sleep-wake abnormalities in patients with cirrhosis'. WILEY-BLACKWELL JOURNAL OF SLEEP RESEARCH, Tallinn, ESTONIA: 22nd Congress of the European-Sleep-Research-Society 23, pp. 146-146.
  • Darling AL, Hart KH, Skene DJ, Arber S, Lanham-New SA. (2014) 'Vitamin D status, functional ability and muscle strength in older South Asian and Caucasian women in the UK'. CAMBRIDGE UNIV PRESS PROCEEDINGS OF THE NUTRITION SOCIETY, 73 (OCE1), pp. E23-E23.
  • Darling AL, Hart KH, Skene DJ, Arber S, Lanham-New SA. (2013) 'Vitamin D, sunlight exposure, sleep disturbances and musculoskeletal health of older South Asian women in the UK: biological and social influences'. CAMBRIDGE UNIV PRESS PROCEEDINGS OF THE NUTRITION SOCIETY, 72 (OCE4), pp. E187-E187.
  • Darling AL, Gossiel F, Hannon R, Skene DJ, Hart KH, Berry JL, Eastell R, Lanham-New SA. (2011) 'An association between seasonal fluctuation 'cycling' of 25(OH)D and increased bone resorption but not BMD or BMC in UK South Asian and Caucasian women living at 51on'. ELSEVIER SCIENCE INC BONE, Athens, GREECE: 3rd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society 48, pp. S187-S187.
  • Darling A, Gossiel F, Hannon R, Skene D, Berry J, Eastell R, Lanham-New S. (2011) 'EVIDENCE FOR AN ASSOCIATION BETWEEN SEASONAL FLUCTUATION OF 25(OH)D AND SERUM C-TELOPEPTIDE (CTX): PRELIMINARY EVIDENCE FROM THE D-FINES STUDY'. SPRINGER LONDON LTD OSTEOPOROSIS INTERNATIONAL, Valencia, SPAIN: 1st IOF-ESCEO Pre-Clinical Symposium 22, pp. 326-326.
  • Darling AL, Skene DJ, Lanham-New SA. (2011) 'Preliminary evidence of an association between vitamin D status and self-assessed sleep duration but not overall sleep quality: results from the D-FINES study of South Asian and Caucasian pre- and post-menopausal women living in Southern England'. CAMBRIDGE UNIV PRESS PROCEEDINGS OF THE NUTRITION SOCIETY, 70 (OCE3), pp. E88-E88.
  • Darling A, Gossiel F, Hannon R, Skene D, Berry J, Eastell R, Lanham-New S. (2010) 'ASSOCIATION BETWEEN DEGREE OF SEASONAL FLUCTUATION ('CYCLING') OF 25(OH)D, PTH AND BONE RESORPTION IN UK SOUTH ASIAN AND CAUCASIAN WOMEN LIVING AT 51 degrees N (SURREY)'. SPRINGER LONDON LTD OSTEOPOROSIS INTERNATIONAL, Liverpool, ENGLAND: Osteoporosis Conference 21, pp. S516-S517.
  • Pagani L, Moriggi E, Revell VR, Hack LM, Izakovic J, Lockley SW, Arendt J, Wirz-Justice A, Cajochen C, Skene DJ, Brown SA, Eckert A. (2009) 'Human molecular circadian rhythms and ageing'. GEORG THIEME VERLAG KG PHARMACOPSYCHIATRY, Munich, GERMANY: 26th Symposium of the Association-of-Neuropsychopharmacology-and-Pharmacopsychiatry (AGNP) 42 (5), pp. 235-235.
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2009) 'PLASMA CORTISOL PROFILES IN PATIENTS WITH CIRRHOSIS: BEWARE THE TIME OF SAMPLING'. B M J PUBLISHING GROUP GUT, Glasgow, SCOTLAND: Annual Meeting of the British-Society-of-Gastroenterology 58, pp. A76-A76.
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2009) 'HEPATO-ADRENAL SYNDROME: DOES CORTISOL SAMPLE TIME MATTER?'. ELSEVIER SCIENCE BV JOURNAL OF HEPATOLOGY, Copenhagen, DENMARK: 44th Annual Meeting of the European-Association-for-the-Study-of-the-Liver 50, pp. S84-S84.
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2008) 'EVIDENCE OF CENTRAL CIRCADIAN DISRUPTION IN PATIENTS WITH CIRRHOSIS'. JOHN WILEY & SONS INC HEPATOLOGY, San Francisco, CA: 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases 48 (4), pp. 1063A-1063A.
  • Montagnese S, Middleton B, Skene DJ, Morgan MY. (2008) 'Sleep disturbances are not a feature of hepatic encephalopathy'. ELSEVIER SCIENCE BV JOURNAL OF HEPATOLOGY, Milan, ITALY: 43rd Annual Meeting of the European-Association-for-the-Study-of-the-Liver 48, pp. S40-S40.
  • Montagnese S, Middleton B, Skene DJ, Morgan MY. (2007) 'Sleep-wake abnormalities do not correlate with neuropsychiatric performance in patients with cirrhosis'. JOHN WILEY & SONS INC HEPATOLOGY, Boston, MA: 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases 46 (4), pp. 562A-563A.
  • Jones KH, Ellis J, Von Schantz M, Skene DJ, Dijk D, Archer SN. (2006) 'Age-related change in the association between a variable number tandem repeat polymorphism in the (PER3) gene and preferred timing of sleep and waking activities'. BLACKWELL PUBLISHING JOURNAL OF SLEEP RESEARCH, Innsbruck, AUSTRIA: 18th Congress of the European-Sleep-Research-Society 15, pp. 97-98.
  • Montagnese S, Middleton B, Mani AR, Skene DJ, Morgan MY. (2006) 'Evidence of central circadian disruption in patients with cirrhosis'. ELSEVIER SCIENCE BV JOURNAL OF HEPATOLOGY, Vienna, AUSTRIA: 41st Annual Meeting of the European-Association-for-the-Study-of-the-Liver 44, pp. S276-S276.
  • Zawilska JB, Lorenc A, Berezinska M, Vivien-Roels B, Pevet P, Skene DJ. (2006) 'Daily oscillation in melatonin synthesis in the turkey pineal gland and retina: Diurnal and circadian rhythms'. TAYLOR & FRANCIS INC CHRONOBIOLOGY INTERNATIONAL, Frankfurt, GERMANY: 10th Congress of the European-Pineal-and-Biological-Rhythms-Society 23 (1-2), pp. 341-350.
  • Montagnese S, Middleton B, Mani A, Skene D, Morgan MY. (2005) 'Plasma melatonin abnormalities in patients with cirrhosis reflect both hepatic and cerebral dysfunction'. JOHN WILEY & SONS INC HEPATOLOGY, San Francisco, CA: 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases 42 (4), pp. 755A-755A.
  • Abi-Saab WM, Skene DJ, Stiger TR, McRobie C, Middleton B, Kaplan IV, Soares HD, Saltarelli MD. (2004) 'Attenuation of the effects of light on nocturnal melatonin production in humans by the selective NK1 receptor antagonist CP-122,721'. ELSEVIER SCIENCE INC BIOLOGICAL PSYCHIATRY, NEW YORK, NY: 59th Annual Meeting of the Society-of-Biological-Psychiatry 55, pp. 40S-40S.
  • Archer SN, Robillard DL, Skene DJ, Smits M, Williams A, Arendt J, von Schantz M. (2003) 'A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference'. AMER ACADEMY SLEEP MEDICINE SLEEP, CHICAGO, ILLINOIS: 17th Annual Meeting of the Associated-Professional-Sleep-Societies 26, pp. A109-A109.

Book chapters

  • Skene DJ. (2003) 'Optimization of light and melatonin to phase-shift human circadian rhythms'. BLACKWELL PUBLISHING LTD 15, pp. 438-441.
  • Skene DJ, Lockley SW, Arendt J. (1999) 'Use of melatonin in the treatment of phase shift and sleep disorders'. KLUWER ACADEMIC/PLENUM PUBL 467, pp. 79-84.
  • Lockley SW, Skene DJ, Thapan K, English J, Ribeiro D, von Schantz M, Arendt J. (1999) 'Extraocular light exposure does not suppress plasma melatonin in humans'. SPRINGER , pp. 403-406.
  • Lockley SW, Skene DJ, Arendt J. (1998) 'Changes in sleep in relation to circadian phase in the blind'. ELSEVIER SCIENCE BV 1152, pp. 247-252.
  • Skene DJ, Lockley SW, Tabandeh H, DeFrance R, Bird AC, Arendt J. (1997) 'Visual pathology and human circadian rhythms'. P J D PUBLICATIONS LTD , pp. 349-353.
  • Deacon S, Skene D, Arendt J. (1996) 'Use of light and/or melatonin in adaptation to phase shifts'. WALTER DE GRUYTER , pp. 398-405.
  • Skene DJ, Deacon S, Arendt J. (1996) 'Use of melatonin in circadian rhythm disorders and following phase shifts'. NENCKI INST EXPERIMENTAL BIOLOGY 56, pp. 359-362.

    Abstract

    Following abrupt phase shifts (real or simulated time zone changes, night shift work) there is desynchronisation between the internal circadian rhythms (including melatonin) and the external environment with consequent disturbances in sleep, mood and performance. In humans the pineal hormone melatonin has phase-shifting and resynchronising properties with regard to a number of circadian rhythms. Suitably timed melatonin adrninstration hastened adaptation to phase shift and significantly improved self-rated jet lag in large numbers of time zone travellers. Preliminary results in night shift workers showed improved daytime sleep and night-time alertness. In simulated experiments, appropriately timed melatonin improved subjective sleep, alertness and performance and facilitated the readaptation of the melatonin rhythm following a rapid 9 h advance phase shift. Melatonin has also been assessed in circadian rhythm disorders with disturbed sleep (blindness and delayed sleep phase insomnia). Compared with placebo, melatonin significantly improved sleep and synchronised the sleep wake cycle in some blind subjects. Melatonin treatment significantly advanced the sleep onset time in delayed sleep phase insomnia. Taken together these findings suggest that melatonin is of benefit in facilitating adaptation to forced phase shifts and in conditions of circadian rhythm disturbance.

  • SKENE DJ, RAYNAUD F, PEVET P. (1993) 'MELATONIN AND 5-METHOXYTRYPTOPHOL BINDING-SITES IN THE RETINA'. ELSEVIER SCIENCE PUBL B V 1017, pp. 87-94.
  • SKENE DJ. (1992) 'N-ACETYLTRANSFERASE AND MELATONIN IN THE RETINA - REGULATION, FUNCTION AND MODE OF ACTION'. PORTLAND PRESS 20, pp. 312-315.

Reports

  • von Schantz M, Skene DJ. (2015) Telling biological time from a blood sample: current capabilities and future potential. SAGE PUBLICATIONS INC , pp. 699-701.

Other publications

  • Revell VL, Skene DJ. (2008) Authors' response. Chronobiology International, 25 (4), pp. 655-656.

Posters

  • Darling AL, Gossiel F, Hannon R, Skene DJ, Berry JL, Eastell R, Lanham-New SA. (2010) ASSOCIATION BETWEEN DEGREE OF SEASONAL FLUCTUATION (‘CYCLING’) OF 25(OH)D, PTH AND BONE RESORPTION IN UK SOUTH ASIAN AND CAUCASIAN WOMEN LIVING AT 51ON (SURREY). National Osteoporosis Society 2010 Liverpool
  • Darling AL, Gossiel F, Hannon R, Skene DJ, Berry JL, Eastell R, Lanham-New SA. (2010) Evidence for an Association Between Seasonal Fluctuation of 25(OH)D and Serum C-telopeptide (CTx): Preliminary Evidence from the D-FINES study.. ASBMR Annual Meeting San Diego September 2010

Theses and dissertations

  • Darling AL. (2014) Vitamin D, light exposure, sleep and musculoskeletal health in South Asian and Caucasian women: biological and social influences.

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