52-OR: Intrinsically Photosensitive Retinal Ganglion Cell Dysfunction in Diabetic Retinopathy Associates with Impaired Sleep and Circadian Rhythms
Sirimon ReutrakulJason C. ParkFelix Y. ChauTracy BaynardMedha PriyadarshiniStephanie J. CrowleyJ. Jason McAnany
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Background: Intrinsically photosensitive retinal ganglion cells (ipRGCs) control the pupillary light reflex (PLR) and synchronize sleep-wake cycles, melatonin secretion, and metabolic processes to the 24-h day. PLR abnormalities in diabetic retinopathy (DR) suggest ipRGC dysfunction. We explored whether ipRGC dysfunction in DR is associated with impaired sleep, circadian rhythms and metabolic functioning. Methods: Healthy controls (n=6), type 2 diabetes (T2D) without DR (n=8), or T2D with at least moderate DR (n=11) participated. PLR inferred ipRGC function, HbA1c, and nocturnal urinary 6-sulfatoxymelatonin (aMT6s/creatinine ratio) were measured. Sleep was recorded by 7-day actigraphy. Dim light melatonin onset (DLMO) was assessed by sampling saliva in the 7 hours before self-reported bedtime. Results: Mean age was 54.6±5.4 yr. The relative PLR was significantly smaller in T2D-DR (control vs. T2D-noDR vs. T2D-DR: 0.32(0.10) vs. 0.26 (0.09) vs. 0.13 (0.11), p=0.003). Nocturnal aMT6s [8.3 (3.1) vs. 14.6 (14.3) vs. 1.9 (2.1) ng/mg, p=0.001] was significantly lower in T2D-DR. Sleep was more disturbed in T2D-DR than others as reflected by higher wake time after sleep onset (p=0.024), higher fragmentation index (p=0.007) and lower sleep efficiency (p=0.030). HbA1c was similar between T2D groups. T2D-DR were more likely to have no detectable rise of salivary melatonin in the evening (normal 16% vs. DM-noDR 14% vs. DM-DR 67%, p=0.049). Smaller PLRs correlated with lower aMT6s (r=0.652, p=0.001). Among T2D, lower aMT6s and smaller PLR associated with lower sleep efficiency (p=0.029-0.046) and more fragmented sleep (p=0.028-0.066). There was no relationship between PLR or aMT6s with HbA1c in T2D. PLR was smaller in those without vs. with DMLO [0.11 (0.09) vs. 0.29 (0.09), p<0.001]. Conclusion: T2D with DR had dysregulated melatonin rhythm and disrupted sleep, which significantly correlated with the degree of ipRGC dysfunction. Disclosure S. Reutrakul: None. J.C. Park: None. F. Chau: None. T. Baynard: None. M. Priyadarshini: None. S. Crowley: None. J. McAnany: None. Funding University of Illinois at ChicagoKeywords:
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Given the impact of sleep in several domains of a child's development, the comparison between actigraphy and parental questionnaires is of great importance in preschool-aged children, an understudied group. While parental reports tend to overestimate sleep duration, actigraphy boosts the frequency of night-waking's. Our primary goal was to compare actigraphy data and parental reports (
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(1) To examine toddler sleep in a low-income sample by comparing sleep diaries and actigraphy and (2) to assess whether toddlers are meeting the National Sleep Foundation recommendations (11-14 hours of sleep/24 hours and bedtime before 9 PM).A convenience sample of mother-toddler dyads was recruited from 2 health care sites serving low-income communities. An actigraph was placed on the toddler's ankle and was worn for 3 days and nights. Mothers concurrently completed a sleep diary. Bedtime, nighttime sleep duration, nap duration, and 24-hour sleep duration were collected by both measures. Actigraphy data were analyzed using a combination of manufacturer's scoring algorithm and manual editing. Descriptive statistics and paired samples t-tests were conducted to examine the differences between sleep estimates by a sleep diary and actigraphy.Twenty toddlers (aged 13-42 months) were included in the analyses. Based on actigraphy, 1 toddler went to bed by 9 PM on all 3 nights. Six toddlers achieved 11 to 14 hours of sleep measured in a 24-hour period for 1 of the 3 days, but when sleep was averaged across the study, none achieved this goal. Compared with actigraphy, sleep diaries underestimated bedtime by 1 hour, overestimated nighttime sleep duration by 2.5 hours, and overestimated 24-hour sleep duration by 2.3 hours, on average for all 3 nights.Mothers reported significantly earlier bedtimes and longer sleep durations for their toddlers compared with actigraphy, suggesting that objective measures differ from sleep diaries in assessing sleep in toddlers from low-income families. Findings should not be generalized to populations of low-income families without replication.
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Patients receiving home parenteral nutrition (HPN) frequently report disrupted sleep. However, there are often inconsistencies between objectively measured and questionnaire-derived sleep measures. We compared sleep measures estimated from wrist actigraphy and self-report in adults receiving HPN.
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Chronic sleep onset insomnia with late melatonin onset is prevalent in childhood, and has negative daytime consequences. Melatonin treatment is known to be effective in treating these sleep problems. Bright light therapy might be an alternative treatment, with potential advantages over melatonin treatment. In this study, we compare the effects of melatonin and bright light treatment with a placebo condition in children with chronic sleep onset insomnia and late melatonin onset.Eighty-four children (mean age 10.0 years, 61% boys) first entered a baseline week, after which they received melatonin (N = 26), light (N = 30), or placebo pills (N = 28) for 3 to 4 weeks. Sleep was measured daily with sleep diaries and actigraphy. Before and after treatment children completed a questionnaire on chronic sleep reduction, and Dim Light Melatonin Onset (DLMO) was measured. Results were analyzed with linear mixed model analyses.Melatonin treatment and light therapy decreased sleep latency (sleep diary) and advanced sleep onset (sleep diary and actigraphy), although for sleep onset the effects of melatonin were stronger. In addition, melatonin treatment advanced DLMO and had positive effects on sleep latency and sleep efficiency (actigraphy data), and sleep time (sleep diary and actigraphy data). However, wake after sleep onset (actigraphy) increased with melatonin treatment. No effects on chronic sleep reduction were found.We found positive effects of both melatonin and light treatment on various sleep outcomes, but more and stronger effects were found for melatonin treatment.
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Actigraphy has gained popularity as an objective method for measuring sleep in a home setting. We evaluated whether missing data affects the utility of actigraphy for the measurement of sleep parameters in normal sleepers.We evaluated actigraphy data from 60 normal sleepers who participated in a study of the effects of changes in setting on sleep. Participants were asked to wear a Mini Mitter Actiwatch actigraph for 35 days and to use event markers to record bedtime and arising time. Counts of nights on which participants failed to supply usable data were computed using the following criteria: missing nights, missing bedtime markers, missing arising time markers, and multiple markers supplied at bedtime or arising time. A night on which any of these problems occurred was counted as unscorable.We evaluated a total of 2,100 nights, of which 559 (27%) nights were deemed unscorable due to missing data. Missing markers at bedtime (206) and arising time (172) accounted for the majority of missing data. Trends over the five weeks indicated that incidence of missing data increased over the assessment period.We found that missing data was a significant problem for long-term assessment of sleep using actigraphy. We suggest that researchers consider compensatory strategies, such as extending the assessment period and using adjunctive measures, in order to obtain sufficient data for analysis. We also recommend that future improvements in actigraphy instruments should aim to address the sources of missing data.
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Introduction: Children with Autism Spectrum Disorder (ASD) suffer from insomnia at much higher rates than typically developing (TD) peers. Research indicates that sleep problems in ASD may be due to hypersensitivities to stimuli and melatonin deficiencies. Behavioral treatments for insomnia in ASD often include sleep hygiene recommendations to avoid physical activity and light intensity within two hours of bedtime. However, despite these recommendations, research examining the relationship between physical activity and light intensity close to bedtime and sleep outcomes in TD and ASD is sparse. The current study examines associations between pre-bedtime light intensity exposure, physical activity, and sleep in children with ASD and in TD children. Methods: Children with ASD (n=28, Mage=8.4, SD=1.7) and 27 TD children (n=27, Mage=8.9, SD=1.8) who met DSM-5 criteria for insomnia disorder completed 14 concurrent days of sleep diaries with parental assistance and 14 days of wrist worn actigraphy. Sleep diaries and actigraphy obtained estimates of sleep onset latency (SOL), wake time after sleep onset (WASO), and total sleep time (TST) for each night, and actigraphy also obtained light intensity exposure and average physical activity in five timeframes prior to bedtime (0-30 minutes, 0-60 minutes, 0-120 minutes, 120-240 minutes, and 240-360 minutes). Multi-level models examined intra-individual and inter-individual associations between pre-bedtime physical activity, light intensity, and subjective/actigraphic sleep outcomes, as well as whether these associations differed between children with ASD and TD. Results: Greater light intensity was associated with longer subjective SOL (B=0.18, p=0.04, 120-240 mins, inter-individual), longer subjective WASO (B=0.05, p<0.001, 120-240 mins, intra-individual), and shorter subjective TST (B=-0.42, p=0.02, 120-240 mins, inter-individual) in TD but not ASD. Greater light intensity was associated with longer subjective SOL (B=0.08, p=0.05, 0-60 mins, intra-individual), and longer subjective TST (B=1.25, p=0.04, 0-120 mins, inter-individual) for ASD, but not TD. Greater light intensity was associated with longer actigraphic SOL (B=0.07, p=0.05, 0-60 mins, inter-individual) in ASD, but not TD, and longer actigraphic WASO (B=0.02, p<0.01, 120-240 mins, intra-individual) in TD, but not ASD. Greater physical activity was associated with longer subjective TST (B=0.30, p=0.01, 0-30 mins, inter-individual; B=0.36, p<0.01, 0-60 mins, inter-individual; B=0.26, p=0.02, 0-120 mins, inter-individual) and shorter actigraphic SOL (B=-0.05, p=0.01, 240-360 mins, intra-individual) in both ASD and TD. Conclusion: Results do not support sleep hygiene recommendations for avoidance of pre-bedtime physical activity, but they generally support avoidance of pre-bedtime light intensity. We speculate that pre-bedtime light intensity exposure may interfere with sleep outcomes through impeding melatonin secretion. Further, our results do not support the mechanism that hypersensitivities to light or physical activity are primarily responsible for insomnia in ASD relative to TD, since both ASD and TD showed similar associations between light, physical activity, and sleep outcomes (i.e., greater pre-bedtime light associated with worse sleep and greater pre-bedtime activity associated with better sleep). Future research should examine the relationship between pre-bedtime light exposure and melatonin production in ASD and explore whether sleep hygiene recommendations to avoid pre-bedtime physical activity are warranted in ASD and TD.
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Abstract Study Objectives Sleep quantity and continuity vary across the lifespan. Actigraphy is a reliable and widely used behavioral measure of sleep in research and personal health monitoring. This meta-analysis provides a novel examination of whether age (in years) is associated with actigraphy-assessed sleep across the lifespan. Methods A systematic search of PubMed, Embase.com, Cochrane CENTRAL, and PsycINFO using “actigraphy” and “sleep” terms provided 7079 titles/abstracts; studies of individuals with known psychiatric or medical comorbidities were excluded. Ninety-one articles (N = 23 365) provided data for six meta-analyses examining sleep duration (k = 89), sleep efficiency (k = 58), bedtime (k = 19) and waketime (k = 9) for individuals ages 6–21, and bedtime (k = 7) and waketime (k = 7) for individuals ages 22 and older. Results At older ages, sleep duration was shorter (r = −0.12) and sleep efficiency was lower (r = −0.05). Older age was associated with later bedtime (r = 0.37) and wake-up time (r = 0.24) from ages 6–21, whereas older age was associated with earlier bedtime (r = −0.66) and wake-up time (r = −0.59) for ages 22 and above. The strength of these associations was modified by study continent, but not by any other moderator. Conclusions Age was negatively associated with actigraphy-assessed sleep duration and efficiency, but the effects were small in magnitude. On the other hand, large associations were observed between age and sleep timing, despite a smaller literature and the absence of analyzable data for ages 30–60. Changes in sleep timing, rather than changes in sleep duration or continuity, may better characterize the effects of age on human sleep.
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Sleep is often quantified using self-report or actigraphy. Self-report is practical and less technically challenging, but prone to bias. We sought to determine whether these methods have comparable sensitivity to measure longitudinal changes in adolescent bedtimes.We measured one week of free-living sleep with wrist actigraphy and usual bedtime on school nights and non-school nights with self-report questionnaire in 144 students at 15 y and 17 y.Self-reported and actigraphy-measured bedtimes were correlated with one another at 15 y and 17 y (p < .001), but reported bedtime was consistently earlier (>30 minutes, p < .001) and with wide inter-method confidence intervals (> ±106 minutes). Mean inter-method discrepancy did not differ on school nights at 15 y and 17 y but was greater at 17 y on non-school nights (p = .002). Inter-method discrepancy at 15 y was not correlated to that at 17 y. Mean change in self-reported school night bedtime from 15 y to 17 y did not differ from that by actigraphy, but self-reported bedtime changed less on non-school nights (p = .002). Two-year changes in self-reported bedtime did not correlate with changes measured by actigraphy.Although methods were correlated, consistently earlier self-reported bedtime suggests report-bias. More varied non-school night bedtimes challenge the accuracy of self-report and actigraphy, reducing sensitivity to change. On school nights, the methods did not differ in group-level sensitivity to changes in bedtime. However, lack of correlation between bedtime changes by each method suggests sensitivity to individual-level change was different. Methodological differences in sensitivity to individual- and group-level change should be considered in longitudinal studies of adolescent sleep patterns.
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The present study compared the course of parent-report and actigraphy-derived sleep profiles over a 1-year period, in school-age children with autism spectrum disorder and typically developing children. The Children’s Sleep Habits Questionnaire and 14 nights of actigraphy were used to assess sleep profiles. Parents also completed the Spence Children’s Anxiety Scale, the Social Worries Questionnaire and the Bedtime Routines Questionnaire. Between-group differences in parent-reported sleep problems were less pronounced at follow-up compared to baseline. The course of objective sleep was comparable between groups, with a significant reduction in sleep duration over time in both groups. Children with autism spectrum disorder were further characterised by significantly more night-to-night variability in sleep quality, across both time points. Reductions over time in parent-reported sleep problems were significantly associated with reduced anxiety. Reductions in actigraphy-derived sleep efficiency were associated with an increased frequency of maladaptive activities in the hour before bedtime, in both children with and without autism spectrum disorder.
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Results: Based on the findings from the questionnaire, parents of children with ADHD reported significantly more sleep problems than parents of normally developing children. However, the majority of these sleep differences were not verified through actigraphy or sleep diary data, with the exception of longer sleep duration for children with ADHD and parent reports that describe increased bedtime resistence. It was also found that child-parent interactions during bedtime routines were more challenging in the ADHD group. Conclusions: Despite the possibility of intrinsic sleep problems such as longer sleep duration, results indicate that many of the sleep problems of children with ADHD may be due to challenging behaviours during bedtime routines. The reason for discrepancies among sleep studies employing objective measures as well as between retrospective and prospective measures are discussed.
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