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Background: Although insufficient sleep has been shown to contribute to obesity-related elevated blood pressure, the circadian timing of sleep has emerged as a novel risk factor. We hypothesized that deviations in sleep midpoint, a measure of circadian timing of sleep, modify the association between visceral adiposity and elevated blood pressure in adolescents. Methods: We studied 303 subjects from the Penn State Child Cohort (16.2±2.2 years; 47.5% female; 21.5% racial/ethnic minority). Actigraphy-measured sleep duration, midpoint, variability, and regularity were calculated across a 7-night period. Visceral adipose tissue (VAT) was measured with dual-energy X-ray absorptiometry. Systolic blood pressure (SBP) and diastolic blood pressure levels were measured in the seated position. Multivariable linear regression models tested sleep midpoint and its regularity as effect modifiers of VAT on SBP/diastolic blood pressure levels, while adjusting for demographic and sleep covariables. These associations were also examined as a function of being in-school or on-break. Results: Significant interactions were found between VAT and sleep irregularity, but not sleep midpoint, on SBP ( P interaction=0.007) and diastolic blood pressure ( P interaction=0.022). Additionally, significant interactions were found between VAT and schooldays sleep midpoint on SBP ( P interaction=0.026) and diastolic blood pressure ( P interaction=0.043), whereas significant interactions were found between VAT and on-break weekdays sleep irregularity on SBP ( P interaction=0.034). Conclusions: A delayed and an irregular sleep midpoint during school and during free-days, respectively, increase the impact of VAT on elevated blood pressure in adolescents. These data suggest that deviations in the circadian timing of sleep contribute to the increased cardiovascular sequelae associated with obesity and that its distinct metrics require measurement under different entrainment conditions in adolescents.

To assess the association of insomnia phenotypes, being insomnia with short sleep duration (ISSD) and insomnia with normal sleep duration (INSD), with suicidality in a randomly selected population-based sample.Data were analyzed from the Penn State Adult Cohort. Participants (N = 1741, 52.5 years, 57.4% female) were randomly recruited from the general population between January 1990 through March 1999 and mortality data were available through December 2018. Insomnia symptoms were defined as self-reports of moderate-to-severe difficulties initiating or maintaining sleep, early morning awakening and non-restorative sleep, or having chronic insomnia (n = 719). Short sleep duration was defined as6 hours of in-lab polysomnography-measured sleep duration (n = 879). Suicidality (SAI; n = 102) was ascertained by a lifetime history of suicidal ideation (SI; n = 84), suicide attempts (SA; n = 48) or death by suicide (DBS; n = 10).Compared to normal sleepers who slept ≥6 hours, participants with ISSD and INSD were associated with 1.72-fold and 2.22-fold increased odds of SAI, respectively; these associations were significant for SI, with 2.09-fold and 2.24-fold increased odds, respectively, but not for SA, after adjusting for physical and mental health comorbidities. ISSD and INSD differed in SAI age of onset and hospitalizations after SA.The results of this cohort study suggest that both INSD and ISSD phenotypes are associated with increased suicidal ideation, while the INSD phenotype has an earlier age of onset and is more likely to experience hospitalizations after attempting suicide. These results highlight the importance of targeting insomnia symptoms to help prevent suicide.

Abstact Study Objectives The long-term effects of sleep health and shift work on cognitive performance are unclear. In addition, research has been limited by small sample sizes and short follow-up periods. We conducted one of the largest examinations of the longitudinal influence of sleep health dimensions and shift work on cognitive performance in people of middle and old age using data from the UK Biobank. The hypothesis was that poor sleep health and shift work would predict lower cognitive performance. Methods Self-reported sleep duration, daytime sleepiness, insomnia symptoms, chronotype, and shift work status were assessed as predictors at baseline. Cognitive performance was operationalized by a touchscreen test battery at follow-up between 7.4 ± 2.2 and 9.0 ± 0.9 years after baseline assessment, depending on the specific task. Models were performed for each cognitive domain including relevant confounders (e.g. depression). The alpha level was set at p Results The study sample comprised 9394 participants for the reasoning task, 30 072 for the reaction time task, 30 236 for the visual memory task, 2019 for the numeric memory task, and 9476 for the prospective memory task. Shift work without night shifts (β = −2.0 × 10−1 ± 6.5 × 10−2, p = 0.002) and with night shifts (β = −1.9 × 10−1 ± 7.2 × 10−2, p = 0.010) predicted a significantly reduced performance in the reasoning task. Short sleep duration (β = −2.4 × 10−1 ± 7.9 × 10−2, p = 0.003) and shift work without night shifts (β = −3.9 × 10−1 ± 1.2 × 10−1, p = 0.002) predicted a significantly lower performance in the task probing prospective memory. Conclusions Our results suggest that, after controlling for confounding variables, shift work, and short sleep duration are important predictors for cognitive performance in people of middle and old age. Further work is required to examine causal mechanisms of the observed associations.

OBJECTIVES/BACKGROUND: Temporomandibular joint disorder (TMD) is a disabling facial pain syndrome with a high prevalence of insomnia that primarily affects women. Insomnia with objective short sleep duration (ISSD) is an emerging phenotype linked to cardiometabolic morbidity and increased mortality. The present report examines the association of ISSD on clinical and laboratory pain and systemic inflammation in TMD. METHODS: We collected baseline data from 128 women with TMD and insomnia as part of a clinical trial evaluating psychological interventions for sleep and pain. Participants completed self-report questionnaires, one-night polysomnography, a 2-week actigraphy assessment, quantitative sensory testing (QST) to assess cold pain tolerance, pain sensitivity and central sensitization and circulating Interleukin-6 levels were measured to assess systemic inflammation. RESULTS: 24.2% (n=31) of the sample met criteria for ISSD [polysomnography (sleep duration

BACKGROUND: Sleep slow wave activity (SWA) peaks during childhood and declines in the transition to adolescence during typical development (TD). It remains unknown whether this trajectory differs in youth with neuropsychiatric disorders. METHODS: We analyzed sleep EEGs of 664 subjects 6 to 21y (449 TD, 123 unmedicated, 92 medicated) and 114 subjects 7–12y (median 10.5y) followed-up at 18–22y (median 19y). SWA (0.4–4 Hz) power was calculated during non-rapid eye movement sleep. RESULTS: TD and unmedicated youth showed cubic central and frontal SWA trajectories from 6 to 21y (p-cubic

Introduction: Adequate sleep has been recognized by AHA as part of Life’s Essential 8 in the prevention of cardiovascular disease (CVD). The circadian system, which governs the sleep-cycle, is also involved in cardiac, metabolic and autonomic regulation. Heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict CVD. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may impact CAM and be a potential risk factor for adverse CVD outcomes in early life. Hypothesis: We hypothesize that deviations in the circadian timing of sleep are associated with blunted HRV in adolescents. Methods: We analyzed data from 337 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-sleep duration and sleep midpoint (SM) were calculated as the intra-individual mean total sleep time and midpoint of the sleep period, respectively. ACT-sleep variability and sleep regularity (SR) were calculated as the intra-individual standard deviation of sleep duration and sleep midpoint across nights, respectively. Frequency and time-domain HRV indices, including HR oscillations at high frequencies (HF), standard deviation between normal heart beats or R-R intervals (SDNN), and root mean square of successive differences between normal heartbeats (RMSSD), were primary outcomes. Linear regression models tested SM and SR as predictors of HRV indices, while accounting for sex, race/ethnicity, age, body mass index, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results: While there were no meaningful associations between SM or SR with daytime HRV, there were significant associations between SM with nighttime HRV. A later SM was associated with lower nighttime Log-HF, SDNN and RMSSD, yet higher nighttime LF/HF (all p Conclusions: A delayed sleep phase is associated with impaired CAM in adolescents. These data support that circadian misalignment of the sleep-wake cycle may independently contribute to CVD risk.

Introduction Nightmares are common in childhood and typically become less prevalent in adulthood. However, little is known about the natural course of nightmares as children grow into adulthood. The purpose of this study was to examine the longitudinal trajectory of nightmares from childhood to adulthood to determine population-based remission, incidence, and persistence rates. Methods The Penn State Child Cohort is a random, population-based sample of 700 children (5-12 years at baseline) who returned for follow-up visits during adolescence and young adulthood. For the current study, 258 young adults (25.1±2.7 years old, 53.9% female, 24.8% minority population) completed their follow-up visit (15.9±2.0 years later). Nightmares were defined by parent-report in childhood and self-report in adulthood, based on severity. Rates of persistence, remission, and incidence for nightmares were computed. Results The persistence rate was 28% for mild childhood nightmares and 23% for moderate-to-severe childhood nightmares. About 13% of children with mild nightmares experienced a worsening into moderate-to-severe adult nightmares. The full remission rates was 58% and 32% for mild and moderate-to-severe severe childhood nightmares, respectively. About 45% of children with moderate-to-severe severe nightmares experienced partial remission into mild adult nightmares. Among children without nightmares, 32% and 8% developed mild and moderate-to-severe nightmares, respectively, in adulthood. Conclusion Moderate-to-severe nightmares only fully remit in about a third of children in by young adulthood. In addition, about one out of ten children with mild nightmares will worsen in severity by young adulthood. Furthermore, a significant number of children will newly-develop significant nightmares in young adulthood. Given the association of nightmares with adverse mental health outcomes, nightmares should become a focus of independent research and prevention practices. Support (if any) National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)

Introduction Nightmares are highly comorbid with insomnia and have been associated, yet not consistently, with distinct polysomnographic (PSG) disturbances, such as reduced total sleep time (TST), sleep efficiency and slow wave sleep as well as increased nocturnal awakenings and wake after sleep onset (WASO) or abnormal REM sleep. However, most prior studies have relied on a single night of PSG and the degree of stability of sleep parameters or overall differences between individuals with nightmares comorbid with insomnia disorder (NCI), individuals with chronic insomnia disorder (CID) and otherwise good sleeping controls (GSC), remain unknown. Therefore, the aim of this study was to determine if there were significant differences amongst these aforementioned groups in the way their sleep changes across time while being studied in the lab. Methods A total of 142 GSC, 126 CID and 24 NCI participants underwent 8-hour PSG recordings for 4 consecutive nights. Outcomes included sleep continuity, architecture, and REM-related parameters across nights 1 through 4. Intraclass correlation coefficients (ICC) with mixed-effect variances and repeated-measure analysis of variance (ANOVA) were used to determine short-term stability as well as between-subjects and time-by-group interaction effects, respectively. Results ICC were similar across groups on all outcomes (ICCs>0.6) except that the NCI group did not display stability for WASO, stage 1 sleep, REM latency or REM interval. There were no significant time-by-group interaction effects on PSG parameters (ps>0.05). There were significant between-group effects for SOL, number of awakenings, WASO, TST, REM latency, and number of REM episodes (all ps< 0.05), where the NCI group showed significantly longer SOL (58.10±11.08), shorter TST (6.64 hours±1.02), and less REM episodes (3.81±0.76). Conclusion This study suggests greater night-to-night variability and overall disturbance in nighttime sleep continuity and REM sleep in individuals with NCI. These disturbances may be attributed to the occurrence of nightmares, causing wakefulness out of REM sleep, as well as a greater level of hyperarousal as evidenced by the greater SOL and reduced TST, relative to the other groups. These data also suggest the utility of objective sleep measures in nightmare research and clinical practice alike. Support (if any) National Institutes of Health (UL1TR000127)

Introduction The odds ratio product (ORP), a continuous spectral EEG measure of sleep depth, increases in the transition to adolescence and with psychiatric/behavioral disorders; however, its association with cardiac physiology has been largely unexplored. Heart rate variability (HRV), a continuous spectral EKG measure of cardiac autonomic balance, includes HR oscillations at low frequencies (LF), the standard deviation between normal heart beats or R-R intervals (SDNN) and root mean square of successive differences between normal heartbeats (RMSSD), reflecting sympathetic vs. parasympathetic tone. We aimed to examine the longitudinal association of non-rapid eye movement (NREM) sleep ORP with 24-hour HRV in adolescents. Methods We studied 606 children (Md=9y), of whom 418 were followed-up as adolescents (Md=16y) from the Penn State Child Cohort. We extracted ORP in NREM sleep and in the 9s following cortical arousals (ORP-9) from 9-hour, in-lab polysomnography (PSG), and frequency and time-domain HRV indices from 24-h Holter EKG monitoring immediately following PSG. We stratified 24-h HRV data into daytime and nighttime periods. Linear regression analyses examined the associations between change in ORP and ORP-9 with adolescent 24-h HRV indices, adjusting for age, race, sex, BMI, metabolic syndrome score, AHI, insomnia symptoms, actigraphy-TST, and childhood nighttime HRV indices. Results While there were no significant associations between ORP and HRV indices in childhood, there were significant longitudinal and cross-sectional associations in adolescence. Longitudinally, a greater increase in ORP since childhood was associated with lower nighttime Log-LF and SDNN in adolescence (both P< 0.05). Similar longitudinal associations were found for ORP-9, with the addition of higher daytime HR and lower daytime SDNN and RMSSD (all P< 0.05). Cross-sectionally, higher ORP and ORP-9 were associated with higher 24-h HR, yet lower Log-LF, SDNN or RMSSD, for both daytime and nighttime periods in adolescence (all P< 0.05). Conclusion Greater developmental declines in sleep depth and increases in arousability during NREM sleep are associated with impaired cardiac autonomic balance in adolescence, independent of sleep apnea, insomnia or insufficient sleep. These data also suggest a coupling between fine-grain spectral measures of the sleeping brain and those of sympathetic/parasympathetic cardiac modulation, which may inform cardiovascular risk early in life. Support (if any) NIH (R01HL136587, R01MH118308, UL1TR000127)

Introduction Several studies have shown that the insomnia with objective short sleep duration (ISSD) phenotype is associated with stage 2 hypertension and type 2 diabetes. We aimed to determine if there is an association between ISSD and metabolic syndrome (MetS). Methods We studied 1,741 adults from the Penn State Adult Cohort (age 20-88 years, 52.3% female, 12.4% racial/ethnic minority) who underwent a 1-night polysomnographic (PSG) evaluation, clinical history, and physical examination. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year, while poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep or early morning awakening. Objective short sleep duration was defined as < 6-hours. MetS was defined by the presence of 3 or more of: BMI≥30 kg/m2, elevated total cholesterol (≥200 mg/dL), triglycerides (≥150 mg/dL), fasting glucose (≥100 mg/dL), or treatment, and blood pressure (≥130/85 mm Hg) or treatment. Logistic regression models examined the odds of developing MetS, while simultaneously adjusting for sex, race, age, alcohol, smoking, sleep-disordered breathing, mental and physical problems, and sampling weight. Results Compared to normal sleepers with normal sleep duration, ISSD was associated with a significantly increased risk of MetS (OR=2.04, 95%CI=1.13-3.70), while insomnia with normal sleep duration (INSD) was not (OR=1.03, 95%CI=0.53-1.99). Neither normal sleepers with short sleep duration nor poor sleeper with normal or short sleep duration were associated with increased risk of MetS. Further analysis of the clustering of the cardiometabolic risk factors revealed that in the ISSD group who had MetS, 94% had elevated blood pressure, 78% had elevated cholesterol, 72% had insulin resistance, 53% had elevated triglycerides, and 53% had BMI≥30 kg/m2. Conclusion These data indicate that hypercholesterolemia, but not hypertriglyceridemia or obesity, contributes to the association of ISSD with MetS. These data suggest that in addition to the previously-identified elevated blood pressure and insulin resistance, treatment of hypercholesterolemia in patients with ISSD may prevent the development of cardiovascular and cerebrovascular disease. Support (if any)

Introduction The RU-SATED model – regularity, satisfaction, alertness, timing, efficiency, and duration – captures the 24-hour experience of sleep to asses multidimensional sleep health (MSH). However, most prior evidence comes from middle-aged adults. We provide updated MSH data in adolescents by leveraging objective and self-reported sleep measures. Methods We studied 377 adolescents (16.4±2.3 yr; 46.4% female; 21.5% racial/ethnic minority) from the Penn State Child Cohort, a randomly-selected population-based sample. Each MSH domain was categorized as “good” or “poor” using cut-offs informed by prior studies and expert consensus. Good cut-offs, assigned a score of 1, that were derived from actigraphy-measured data included: the standard deviation of sleep midpoint ≤1-h (RU), mean of sleep midpoint 2:00-4:00 (T), mean value of sleep efficiency ≥85% (E), and mean total sleep time ≥7.5-h (D). Good cut-offs derived from self-reported rating scales included the absence of insomnia symptoms (S) or excessive daytime sleepiness (A). Values considered poor based on these cut-offs were assigned a score of 0. Scores were summed across all domains to obtain a composite score ranging from 0 to 6, with higher scores indicating better MSH. Morningness and Tanner staging were self-reported, while Sleep and Arousal clusters scores on the Pediatric Behavior Scale were parent-reported. Results The mean composite score was 3.03 ± 1.30 and domains A and D were most commonly rated as poor (64.5% and 65.3%, respectively). Younger age (r=-0.13, p< 0.05) and identifying as non-Hispanic white (r=-0.14, p< 0.01) were significantly associated with higher MSH scores, while sex (r=-0.04, p=0.40), Tanner staging (r=-0.06, p=0.29) or BMI percentile (r=-0.07, p=0.15) were not. Greater morningness (r=-0.29, p< 0.01), less disturbed sleep (r=-0.28, p< 0.01) and higher arousal (r=-0.21, p< 0.01) scores were associated with higher MSH scores. Conclusion Our data-driven approach can be used to assess MSH in the adolescent population. Our definition captures previously identified health disparities in MSH in adults and shows optimal construct validity against self-reports of circadian preference and parent observations of adolescents’ degree of sleep disturbance and arousal. Improving sleep duration and daytime alertness appear to continue to be the most relevant domains impacting overall MSH in adolescents. Support (if any) NIH (R01HL136587,UL1TR000127)

STUDY OBJECTIVES: The Hypersomnia Severity Index (HSI) was designed to assess the severity and impairment of hypersomnolence and has been validated in persons with psychiatric disorders. Little is known about its psychometric properties in clinical samples of patients with sleep disorders. METHODS: One hundred fifty-eight patients (aged 44.1 ± 16.4 years, 29.1% male, 19.6% racial/ethnic minority) evaluated at the Behavioral Sleep Medicine program of the Penn State Health Sleep Research and Treatment Center completed the HSI and other patient-reported outcomes. We examined the HSI’s reliability and factorial, construct, and criterion validity. RESULTS: The HSI showed satisfactory internal consistency (α = 0.79). A 2-factor structure, reflecting symptoms (HSI-S) and impairment, explained 56.2% of the variance. Convergent validity with the Epworth Sleepiness Scale was optimal (r = .65) but greater for HSI-S (r = .69) than for impairment (r = .39). Divergent validity was optimal for HSI-S against unrelated measures of sleep effort, reactivity, and incompatible behaviors (r ≤ .02). Construct validity showed higher scores in patients with central disorders of hypersomnolence and lower scores in patients with chronic insomnia disorder compared to those with other sleep disorders; however, these divergent scores were primarily driven by HSI-S rather than impairment. Criterion validity showed that an HSI-S cutoff score ≥ 8 provided the best balance in sensitivity/specificity (0.82/0.78) to identify central disorders of hypersomnolence (area under the curve, 0.85). CONCLUSIONS: The HSI shows satisfactory indices of reliability and validity in a clinical patient sample. Its construct and criterion validity are supported by its divergent association with other patient-reported outcomes and central disorders of hypersomnolence vs chronic insomnia disorder diagnoses and the adequate sensitivity/specificity of its HSI-S cutoff score to reliably identify central disorders of hypersomnolence. CITATION: Fernandez-Mendoza J, Puzino K, Amatrudo G, et al. The Hypersomnia Severity Index: reliability, construct, and criterion validity in a clinical sample with sleep disorders. J Clin Sleep Med. 2021;17(11):2249–2256.

Sleep apnea is a sleep disorder in which breathing is briefly and repeatedly interrupted. Polysomnography (PSG) is the standard clinical test for diagnosing sleep apnea. However, it is expensive and time-consuming which requires hospital visits, specialized wearable sensors, professional installations, and long waiting lists. To address this problem, we design a smartwatch-based system called ApneaDetector, which exploits the built-in sensors in smartwatches to detect sleep apnea. Through a clinical study, we identify features of sleep apnea captured by smartwatch, which can be leveraged by machine learning techniques for sleep apnea detection. However, there are many technical challenges such as how to extract various special patterns from the noisy and multi-axis sensing data. To address these challenges, we propose signal denoising and data calibration techniques to process the noisy data while preserving the peaks and troughs which reflect the possible apnea events. We identify the characteristics of sleep apnea such as signal spikes which can be captured by smartwatch, and propose methods to extract proper features to train machine learning models for apnea detection. Through extensive experimental evaluations, we demonstrate that our system can detect apnea events with high precision (0.9674), recall (0.9625), and F1-score (0.9649).

This is the first study exploring relationships between sluggish cognitive tempo (SCT) and sleep, internalizing, externalizing, somatic, and cognitive problems in elementary school children using subjective and objective sleep measures. From a population-based sample, 665 children (6–12 years of age) were rated by their mothers on the Pediatric Behavior Scale (PBS) and underwent an overnight polysomnography (PSG) in a sleep laboratory to assess physiologic sleep and its stages. The strongest independent predictors of SCT were maternal ratings of cognitive problems, sleeping more than normal, and somatic complaints, which were more powerful predictors than ratings of reduced sleep, disturbed/fragmented sleep, inattention, impulsivity, hyperactivity, depression, anxiety, oppositional defiant disorder, and conduct disorder. PSG scores were not associated with SCT. The strong predictive power of cognitive problems supports the notion that SCT is related to cognitive deficits, although SCT was also associated with diverse noncognitive problems. The finding that sleeping more than normal was the second strongest predictor of SCT suggests that physiological hypoarousal may help explain the connection between SCT and excessive sleep. The third most powerful predictor of SCT was somatic complaints, which is a critical finding because the association between SCT and somatic problems is under-studied. Results strongly support the SCT construct, including its convergent and divergent validity, internal consistency, and consistent factor composition across diagnostic groups and research samples.

Objectives Traits related to a hyper-reactive arousal system (arousability) and weakened sleep system (sleep reactivity) are considered predisposing factors for insomnia of potential clinical utility. However, research examining the psychometric properties (ie, reliability and validity) of the Arousal Predisposition Scale (APS) and its clinical utility (ie, cut-off scores) among population-based and clinical samples is very limited. Methods A total of 500 adults (41.8% female, 39.1 ± 15.9 years) from the general population in Spain and 217 adults (64.5% female, 46.0 ± 16.1 years) from a clinical sample in the United States completed the APS, as well as measures of sleep reactivity, insomnia severity, anxiety, depression, and stress. Structural equation modeling was used to conduct confirmatory factor analysis (CFA) of the APS. Correlation and receiver operating characteristic (ROC) analyses were used to determine convergent and predictive validity of the APS and its factors. Results The CFAs supported two dimensions of emotional reactivity (APS-ER, 9 items) and trait anxiety (APS-TA, 3 items) in both independent samples. APS-ER was associated with sleep reactivity and performed better than APS-TA when predicting clinically significant sleep reactivity and similarly when predicting clinically significant insomnia severity. Conclusions Our findings support the specificity of emotional reactivity and sleep reactivity as trait predispositions to insomnia, while trait anxiety is a predisposing factor for the comorbidity of insomnia with state anxiety rather than a specific diathesis for insomnia. These data provide further support for the diathesis-stress model of insomnia and, as a transdiagnostic process, its potential etiological link with psychopathology.

Introduction Insomnia with objective short sleep duration (ISSD) has been associated with adverse cardiometabolic outcomes, including hypertension and diabetes. However, data on the association between ISSD and the development of cardiovascular and/or cerebrovascular disease (CBVD) are limited. We aimed to examine whether ISSD is associated with incident CBVD. Methods 1,211 men and women from the Penn State Adult Cohort (56.9% women, 51.82±12.85 years) without CBVD at baseline were followed up for 9.21±4.08 years. Based upon clinical history and physical examination, we defined the presence of CBVD as a history of diagnosis or treatment of heart disease and/or stroke. Insomnia was defined as a complaint of insomnia with a duration ≥ 1 year. Poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, nonrestorative sleep or early morning awakening. Objective short sleep duration was defined as < 6-hours sleep based on a 1-night, 8-hours, in-lab polysomnography. Logistic regression models examined the odds of incident CBVD, while simultaneously adjusting for race, sex, age, BMI, smoking, alcohol use, physical and mental health problems, sleep-disordered breathing and follow-up duration. Results Compared to normal sleepers with normal sleep duration, the highest risk of incident CBVD was in the ISSD group (OR=2.68, 95%CI=1.17-6.14), and the second highest in normal sleepers with short sleep duration (OR=1.65, 95%CI=1.10-2.49). The risk for incident CBVD was not significantly increased, in poor sleepers or those with insomnia with normal sleep duration (INSD). Conclusion Our findings indicate that the combination of short sleep duration with the complaint of chronic insomnia (ISSD) is associated with an additive effect on incident heart disease and stroke. These data add to the cumulative evidence supporting the existence of two insomnia phenotypes and that ISSD is the more severe biological phenotype of the disorder associated with physiologic hyperarousal and cardiovascular morbidity. The diagnostic and treatment implications of insomnia phenotyping based on objective sleep duration will be discussed. Support (if any)

Introduction Multidimensional sleep health (MSH) is a population-based approach to capture the 24-hour experience of sleep by incorporating measures of nighttime sleep and daytime functioning that promote physical and mental well-being. We have updated the existing adolescent MSH model to incorporate objective and subjective sleep measures and, in the present study, examined its utility in identifying associations between MSH and behavioral and emotional well-being. Methods We studied 377 adolescents (16.4 ± 2.3 yr; 46.4% female; 21.5% racial/ethnic minority) from the Penn State Child Cohort, a randomly-selected population-based sample. Using the RU-SATED framework – regularity, satisfaction, alertness, timing, efficiency, and duration – we derived an MSH composite score based on actigraphy-measured and self-reported sleep data. We examined the associations between MSH and scores on both the adolescent version of the Child Behavior Checklist (CBCL) and on the Pediatric Behavior Scale (PBS). CBCL’s internalizing, externalizing, thought and attention problems scores were self-reported, while similar behavioral and emotional cluster scores on the PBS were parent-reported. Results Higher MSH scores were associated with lower thought (r=-0.21, p< 0.001), externalizing (r=-0.18, p< 0.001), attention (r=-0.16, p< 0.01) or internalizing (r=-0.12, p< 0.05) problems. Higher MSH scores were associated with lower scores on the rule-breaking (r=-0.27, p< 0.001) and aggressive (r=-0.21, p< 0.001) externalizing subscales. For the internalizing subscales, higher MSH scores were associated with lower anxious-depressed (r = -0.17, p< 0.01), withdrawn-depressed (r=-0.14, p< 0.01), and somatic complaints (r=-0.12, p< 0.05) scores. Analyses based on parent reports on the more fine-grained PBS cluster scores replicated CBCL’s associations; for example, higher MSH scores were associated with lower depression (r=-0.19, p< 0.01) and inattention (r=-0.12, p< 0.05) as observed by parents. Conclusion Optimal sleep health, when considered as a multidimensional construct, is associated with emotional well-being and better behavioral outcomes in adolescents. Our MSH model, derived from objective and subjective sleep metrics, is able to capture similar trends from self-report and parent-report measures of emotion and behavior. Support (if any) National Institutes of Health (R01HL136587, UL1TR000127)

Introduction Declines in non-rapid eye movement (NREM) sleep slow wave activity (SWA) in the transition to adolescence are indicative of brain maturational changes that parallel a decline in sleep depth, as measured by the novel sleep EEG biomarker odds ratio product (ORP). However, these developmental trajectories and their psychiatric/behavioral associations have lacked replication across multiple time points during the lifespan. Methods We determined the developmental trajectories (median follow-up 15y) of SWA and ORP among 150 participants from the Penn State Child Cohort studied in childhood (median age 9y) through adolescence (median age 16y) into young adulthood (median age 24y). Discrete mixture models for clustering of longitudinal data series was used to compute the probability of a subject belonging to mutually-exclusive 2 or 3 trajectory groups, which were selected based on Bayesian and Akaike Information Criteria. Cochran-Mantel-Haenszel tests were used to compare the proportion of subjects with psychiatric/behavioral disorders across the three developmental trajectories in each sleep EEG biomarker. Results Age-related declines in SWA were observed across two developmental groups, of which one followed a cubic trajectory and one a linear trajectory. This decline in SWA was coupled with age-related increases in ORP across three developmental groups, two of which were quadratic and one was linear. Compared to the shallowest trajectories, the SWA and ORP trajectories with the greatest slopes in the transition to young adulthood had a significantly higher proportion of participants with a history of psychiatric/behavioral disorders (78.6% vs. 53.2% and 80.0% vs. 50.7%, respectively, both p< 0.01). Conclusion Our novel data provide replication for the maturational trajectories of SWA and ORP by including time points across three distinct developmental stages, including young adulthood. Also, our data provide evidence linking the developmental trajectories of SWA and ORP with psychopathology. Young adults with psychiatric/behavioral disorders are associated with a steeper developmental decline in sleep intensity (SWA) and sleep depth (ORP) after adolescence. Support (if any) National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)

Introduction Childhood nightmares have a second increase in incidence in young adulthood, which has been attributed to trauma and psychopathology. As suicide rates are high in young adults and have been associated with nightmares, more research is needed regarding this relationship in this age range. This study aimed to examine the association of nightmares, independent of sleep disturbances, insufficient sleep or trauma-history, with suicidality in young adulthood. Methods The Penn State Child Cohort is a random, population-based sample of 700 children (5-12 years at baseline) studied in the sleep laboratory who returned for follow-up visits during adolescence and young adulthood. For the current study, 258 young adults (25.1±2.7 years old, 53.9% female, 24.8% racial/ethnic minority) completed their follow-up visit 15.9±2.0 years later. Nightmares were ascertained by self-report. The presence of suicidality was ascertained from responses on items querying suicidal ideation and/or attempts via clinically-relevant sources (i.e., MINI structured interview, Child Behavior Checklist Adult Self-Report, and Depression Anxiety and Stress Scale). General linear and logistic regression models adjusted for important covariates. Results Subjects reporting nightmares (n=109) had a significantly higher rate of suicidality (29%) than those absent of nightmares (14%; p=0.002), after adjusting for sex, age, sleep disturbances, sleep duration and trauma history. This rate was even higher (46%) in those reporting moderate-to-severe nightmares (n=24; p< 0.01). The odds of suicidality associated with nightmares were 2.3-fold (95%CI=1.1-4.7), after adjusting for sex, age, sleep disturbances, sleep duration and trauma history (p=0.023); a risk that increased to 6.1-fold (95%CI=2.0-18.6) in those reporting moderate-to-severe nightmares (p=0.001). Conclusion These findings further strengthen previous research that has established nightmares’ significant relationship to increased suicidality, even when controlling for other important risk factors such as sleep disturbances and trauma history. Furthermore, as these results come from a random, population-based sample, it also demonstrates the generalizability of the association between nightmares and suicide. As the search for effective prevention strategies for suicide continues, it will be important to assess for the presence and severity of nightmares in those who express suicidal ideation, especially given the treatable nature of nightmares. Support (if any) National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)

Introduction Although insufficient sleep is a known risk factor for metabolic syndrome (MetS), the circadian timing of sleep is also involved in cardiac and metabolic regulation. As a result, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents, may independently impact the burden of MetS in youth. Methods We analyzed data from 277 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 5 nights of at-home actigraphy (ACT), an in-lab 9-h polysomnography (PSG) and an in-lab dual-energy X-ray absorptiometry (DEXA) scan. Two ACT-measured metrics of circadian misalignment were examined as effect modifiers: sleep midpoint (SM), the intra-individual mean midpoint of the sleep period, and sleep regularity (SR), the intra-individual standard deviation of sleep midpoint. DEXA-measured visceral adipose tissue (VAT) was the primary predictor. A continuous MetS score (i.e., sum of the age and sex adjusted z-scores of waist circumference, blood pressure, HOMA-IR, triglycerides, and HDL cholesterol) was the primary outcome. Linear regression models tested SM and SR as effect modifiers of the association of VAT with MetS, while accounting for sex, race/ethnicity, age, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results A significant interaction was found between VAT and SR on MetS (p-interaction=0.05), while not between VAT and SM (p-interaction=0.15). Among adolescents with high sleep irregularity (≥ 45 minutes; n=164), each standard deviation increase in VAT was associated with 2.4 (0.2) standard deviations increase in MetS (p< 0.01), while this association was weaker among adolescents with low sleep irregularity [< 45 minutes; n=113; β=1.7 (0.3), p< 0.01]. Conclusion An irregular circadian timing of sleep may further increase the impact of visceral adiposity on MetS burden in adolescents. Sleep irregularity, independent of sleep apnea and insufficient sleep, may contribute to the development of cardiometabolic sequelae associated with central obesity. Support (if any) National Institutes of Health (R01HL136587, UL1TR000127) and American Heart Association (23PRE1011962)

Introduction Young adults with Autism Spectrum Disorder (ASD) frequently report a multitude of pervasive sleep and circadian problems, including difficulties initiating and maintain sleep, excessive sleepiness, delayed phase, and irregular sleep–wake schedules. These sleep and circadian problems often occur in unison rather than as isolated problems and further impair social functioning, cognition, mood, and overall quality of life, during a particularly challenging developmental stage. Although sleep and circadian problems have been identified as a critical and unmet public health concern for young adults with ASD, and there is a robust evidence for transdiagnostic sleep interventions, there is a paucity of research on the efficacy of these interventions in young adults with ASD. Methods Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), a patient-centered sleep intervention which has demonstrated improvements in sleep and circadian problems and reduce symptomology in both mental and physical health domains across a variety of mental health disorders, will be adapted and iteratively pilot-tested, so that its contents and service delivery methods are appropriate for young adults with ASD. Qualitative methods (semi-structured interviews) will be used to conduct and analyze feedback from key stakeholders (n=20; 10 dyads of young adults with ASD and their caregivers), and used to directly guide adaptations of TranS-C. Results Preliminary data of 5 young adults (18-24y) with ASD show that these individuals are likely to receive multiple sleep disorder diagnoses at equally similar rates (60% circadian rhythm sleep disorder, 60% insomnia disorder), and concurrently present with comorbid mental health problems (60% anxiety disorder, 60% depression). Conclusion Our preliminary data along with existing studies suggest that (1) sleep and circadian problems experienced by individuals with ASD are multidimensional in nature, (2) negatively impact daytime functioning, both within several cognitive and mental health domains, and (3) require transdiagnostic approaches in individuals with ASD to address the broader range of sleep and circadian dysfunction experienced. Potential adaptations to TranS-C format and delivery may serve as a novel module for promoting intervention adherence and responding to unique features of ASD. Support (if any) Brad Hollinger Autism Research Endowment Award

Introduction Sleep disturbances and depression are highly prevalent in Opioid use disorder subjects treated with buprenorphine. However, the association between sleep disturbances such as insomnia/hypersomnia and depression in the above patient population is not known. The aim of the study is to examine the association between sleep disturbances including insomnia and hypersomnia with depressive disorders in buprenorphine treated opioid use disorder (OUDB) subjects. Methods We studied 92 OUDB (38±11.2y, 49% female, 9% minority) at the Recovery, Advocacy, Empowerment and Service program (RASE) and Internal Medicine clinics of Wellspan (York, PA). Subjects completed the Patient Health Questionaire-9 (PHQ-9), Insomnia Severity Index (ISI), Epworth sleepiness scale (ESS), and opioid craving scale (OCS). Depression was defined as a PHQ 9 score ≥ 10, insomnia with an ISI score of >15 and excessive daytime sleepiness (EDS) with an ESS score of >10. Binary logistic regression analysis evaluated the likelihood of OUDB subjects having depression in relation to insomnia, excessive daytime sleepiness (EDS), opioid craving, duration of opioid use, duration since last use of any illegal substance, number of rehabilitation treatments and buprenorphine dosage. Results No differences between in OUDB subjects with (n=47) and without (n=34) depression were observed in age, duration of opioid dependence, duration of buprenorphine treatment, number of rehabilitation treatments or time since last use of any illegal substance. Subjects with depression had significantly higher ISI (18.2±4.2 verus11.8±6.6, p< 0.01), ESS (11.2±4.7 versus 8.2±4.1, p< 0.01 ) scores and a trend towards higher OCS score (3.2±4.1 verus1.9±2.2, p=0.056) as compared to those without depression. The odds of depression associated with Insomnia and EDS were 8.5 (95%CI=2.3-31.2) and 4.4 (95%CI=1.1-17) times respectively in this patient population. Conclusion Insomnia and hypersomnia are highly associated with depression in buprenorphine treated OUDBs patients. Insomnia and hypersomnia needs to be evaluated early and receive targeted treatment during early abstinence in order to prevent relapse in this patient population. Support (if any) This project is supported by the Junior Faculty Development Program, Penn State College of Medicine

Introduction Although the apnea-hypopnea index (AHI) remains the gold-standard metric of the severity of obstructive sleep apnea (OSA), it is often criticized for its limitations. The odds ratio product (ORP), a continuous standardized measure of sleep depth that ranges from 0 (deep sleep) to 2.5 (full wakefulness), has been proposed as a potential EEG-based alternative to assess the severity of OSA, including its association with cardiovascular outcomes such as elevated blood pressure (eBP). Methods We extracted ORP during rapid eye movement (REM) and non-REM sleep stages from the sleep EEG of 421 adolescents (median 16y) from the Penn State Child Cohort. Higher ORP indicates lower sleep depth. Systolic and diastolic BP levels were measured in the seated position and eBP was identified using American Heart Association guideline-recommended pediatric criteria. OSA was defined as an AHI of 2 or greater events per hour of sleep. Logistic regression models examined the joint of effect of AHI and ORP on eBP, while adjusting for sex, age, race/ethnicity and body mass index, and stratified by the presence of OSA. Results We found a significant interaction between AHI and ORP on eBP (p-interaction=0.016). Among adolescents with OSA, each additional 0.5-point increase in ORP was associated with 6.3-fold odds (95%CI=1.9-20.6, p=0.003) of eBP. Specifically, each additional 0.5-point increase in ORP was associated with 6.4 mmHg (SE=3.0, p=0.036) higher systolic BP among adolescents with OSA. These associations were not significant among adolescents without OSA (eBP: OR=0.8, 95%CI=0.4-1.8, p=0.602 for each additional 0.5 increase in ORP). Conclusion Our data support ORP as a prognostic sleep-EEG metric of OSA in youth. Future clinical trials should examine the added value of ORP in OSA endophenotyping, its response to treatment and role in improving cardiovascular outcomes. Support (if any) National Institutes of Health (R01HL136587, R01MH118308, UL1TR000127)

Introduction Insomnia is the most prevalent sleep disorder, with 10% of adults meeting criteria for a chronic insomnia disorder (CID). Cognitive-behavioral therapy for insomnia (CBT-I) is the first-line recommended treatment given the strong evidence supporting its efficacy in the short-term and mid-term. Less is known about the effectiveness of CBT-I in routine clinical practice on patient-reported outcomes beyond 3y post-treatment. Methods Participants included 68 adults (48±15 years old, 63% female, and 11% minority) who received CBT-I for CID at the Behavioral Sleep Medicine (BSM) program of Penn State Health Sleep Research & Treatment Center3 to 7y prior to the present study. Participants completed Insomnia Severity Index (ISI) and Flinders Fatigue Scale (FFS) at baseline and follow up. Results After a median of 5y follow-up, 50% of patients didn’t meet insomnia case definition (ISI< 11), and 60% had experienced a meaningful improvement in insomnia severity (change in ISI score of -6 points or more). Only 35% of patients continued to experience moderate-to-severe insomnia (ISI>14) at follow-up. These effects were similar in patients who had a history of a medical (n=42) or psychiatric (n=38) disorder at pre-treatment when compared to those without prior medical or psychiatric disorders (p=0.380 and p=0.467 for insomnia caseness, respectively). The percent of patients absent of clinically significant daytime fatigue (FFS< 13) increased from 29% to 50 after the same period of long-term follow-up, and those with moderate-to-severe daytime fatigue (FFS>15) fell from 62% to 38%. Hypnotic use (i.e., prescription or over-the-counter) decreased from 66% at baseline, though this varied by insomnia status at follow-up: while 56% of insomnia cases (n=34) at follow-up reported still taking medications at bedtime, only 17% of remitted cases (n=34) did (p< 0.001). Conclusion This long-term evidence is consistent with prior clinical trials, national trends, and further supports that insomnia is a disorder, not a symptom, comorbid with medical and psychiatric conditions that should be treated independently. The effectiveness outcomes show improved sleep, daytime functioning, and discontinuation of sleep medications, a goal of clinical practice guidelines. Importantly, treatment gains remained after the onset of the COVID-19 pandemic. Support (if any) Penn State Health Department of Psychiatry Trainee Award

Introduction Insomnia with objective short sleep duration (ISSD) has been proposed as the most biologically severe phenotype of the disorder associated with cardiometabolic morbidity in population-based samples. Methods In this study, we investigated the association between ISSD and hypertension in a large clinical sample. We studied 348 patients diagnosed with chronic insomnia disorder (CID) based on International Classification of Sleep Disorders (ICSD-3) criteria and 150 normal sleepers. Objective short sleep duration was defined by the median total sleep time (TST) of the sample (< 7 hours) measured with 1-night polysomnography. Hypertension was defined based on blood pressure (BP) levels, antihypertensive medication use and/or a physician diagnosis. Results After adjusting for potential confounders, patients with CID who slept < 7 hours were associated with 2.8-fold increased odds of hypertension compared to normal sleepers who slept ≥7 hours (odds ratio [OR]=2.81, 95% confidence interval [95%CI]=1.068–7.411) or < 7 hours (OR=2.75, 95%CI=1.005-7.542), whereas patients with CID who slept ≥ 7 hours (OR=1.52, 95%CI=0.537-4.285) or normal sleepers who slept < 7 hours (OR=1.07, 95%CI=0.294-3.904) were not significantly associated with increased odds of hypertension compared to normal sleepers who slept ≥ 7 hours. Linear regression analyses showed that, for every hour decrease in TST, systolic and diastolic blood pressure increased by 1.014 mmHg (p=0.045) and 0.923 mmHg (p=0.015), respectively, in patients with CID but not in normal sleepers. Conclusion Our findings further support that ISSD is a risk factor for hypertension and objective short sleep duration may be a useful marker of the biological severity of CID in clinical practice. Support (if any) This study was supported by the National Natural Science Foundation of China (81970087), Guangdong Province Science and Technology Special Fund Project (200115165870512), and the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (2020LKSFG05B). The authors report no conflict of interest.

Introduction While nightmares are well known to be associated with greater sleep disturbance and psychopathology relative to insomnia, this has primarily been observed in experimental samples and not well-studied in outpatient clinical samples. Several theories for the etiology and maintenance of nightmares have identified the roles of both hyperarousal and emotion dysregulation in explaining the association of nightmares to adverse psychiatric outcomes. Given that insomnia is also associated with similar predisposing and perpetuating factors such as greater trait arousability and sleep reactivity, it is important to understand how these factors compare between nightmares and insomnia. Methods A total of 445 patients (45.6±18.4 years old, 66.5% female, 13.0% minority) with diagnoses of nightmare disorder (n=32), insomnia disorder (n=274) and any other sleep disorder (n=139) were evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Health Sleep Research & Treatment Center. To measure symptoms of depression, anxiety, stress, hyperarousal, sleep reactivity, and dysfunctional beliefs about sleep, all patients completed the Depression Anxiety Stress Scale (DASS), Arousal Predisposition Scale (APS), Ford Insomnia Response to Stress Test (FIRST), Pre-sleep Arousal Scale, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS), respectively. Analysis of variance (ANOVA) examined between-group differences in patient-reported outcomes. Results There were no significant between-group differences on sleep reactivity, pre-sleep cognitive arousal, dysfunctional beliefs and attitudes about sleep or depression scores (all ps>0.12). However, patients with nightmare disorder showed greater arousability, in both trait anxiety and emotional reactivity, pre-sleep somatic symptoms, anxiety and perceived stress than patients with insomnia disorder or with any other sleep disorder (all ps< 0.05). Conclusion While patients with nightmare disorder share predisposing and perpetuating factors common to patients with insomnia disorder, they do present with more severe forms of cognitive-emotional arousability, trait-anxiety, and somatic symptoms of anxiety that impact nighttime sleep. These data suggest that clinical evaluations for sleep disruption should include a thorough gathering of history to include the onset, course, and perpetuating factors. Cognitive-behavioral therapies for nightmares and insomnia should be tailored to target these specific factors in order to prevent relapses. Support (if any)

Introduction The circadian timing system, which governs the sleep-wake cycle, is involved in cardiometabolic and autonomic regulation. Heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict cardiovascular morbidity. Therefore, circadian misalignment of the sleep-wake cycle, which is highly prevalent in adolescents and may express differently if youth are in school or free-days, is likely to impact CAM. We examined whether deviations in the circadian timing of sleep are associated with blunted HRV in adolescents as a function of being entrained to school or not. Methods We studied 337 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-measured sleep midpoint (SM) was calculated as the midpoint of the sleep period for weekdays (5-nights) and weekends (2-nights), whereas ACT-measured sleep regularity (SR) was calculated as the intra-individual standard deviation of the SM across 5- and 7-nights. Frequency and time-domain HRV indices were primary outcomes. Linear regression models were stratified by “in school” and “on break” to test SM and SR as predictors of HRV indices while accounting for sex, race/ethnicity, age, BMI percentile, ACT-sleep duration, ACT-sleep variability, and PSG-apnea/hypopnea index. Results Lower SR on schooldays was associated with lower nighttime Log-HF, Log-LF and SDNN, yet higher HR (all p< 0.01); e.g., each standard deviation increase in SR on schooldays (i.e., 45m higher) was associated with -7.15ms (2.57) in nighttime SDNN (p=0.006). A later SM on free weekends was associated with lower nighttime Log-HF, Log-LF, SDNN and RMSSD, yet higher HR and LF-HF ratio (all p< 0.03); e.g., each standard deviation increase in SM on free weekends (i.e., 1.5h later) was associated with -7.33ms (2.85) in nighttime RMSSD (p=0.011). Conclusion A delayed and an irregular sleep midpoint during breaks and during schooldays, respectively, were associated with impaired CAM in adolescents. These data suggest that not only circadian misalignment contributes to adverse cardiovascular outcomes but its distinct metrics require measurement under different entrainment conditions in adolescents. Support (if any) NIH (R01HL136587,R01MH118308,UL1TR000127), American Heart Association (23PRE1011962).

Study objectives We investigated the moderation of caloric intake on the association between race/ethnicity and habitual sleep in adolescents. Methods We analyzed the data obtained from 324 adolescents who completed the follow-up examination of the Penn State Child Cohort study. We collected actigraphy-measured sleep duration on 7 consecutive nights and computed their mean and standard deviation as habitual sleep duration (HSD) and habitual sleep variability (HSV), respectively. We also measured participants’ daily intakes of total calorie, total fat, carbohydrates, and protein, through the Youth/Adolescent Food Frequency Questionnaire. Adjusted mean HSD and HSV among non-Hispanic whites and racial/ethnic minorities were compared by using analysis of covariance (ANCOVA), while controlling for age, sex, BMI percentile, total caloric intake, and socioeconomic status. The significance of the interaction between race/ethnicity and caloric intake was further tested in ANCOVA models. Results The study sample consisted of 79.3% non-Hispanic whites, 13.0% African American, 4.6% Hispanics, 2.2% Asian, and 0.9% American Indian. Adolescents who are racial/ethnic minorities showed shorter HSD (mean (SE): 6.80 (0.10) vs. 7.07 (0.05) hours/night, p = 0.02) and higher HSV (mean (SE): 1.31 (0.07) vs. 1.15 (0.04) hours/night, p = 0.04) than non-Hispanic whites. Racial/ethnic differences in HSV were significantly more pronounced among adolescents with high caloric intake (p interaction = 0.01), especially from carbohydrates (p interaction = 0.03) and fat (p interaction = 0.05). Conclusion Adolescents who are racial/ethnic minorities slept objectively shorter and with greater night-to-night variability than non-Hispanic whites. The racial/ethnic disparity in habitual sleep variability was more pronounced among adolescents with high caloric intake, particularly from carbohydrates and fat.

BACKGROUND: Current drug treatments have limited efficacy and intolerable side effects in advanced-to-end-stage Parkinson’s disease (advPD). D(1) agonists have the potential to provide symptomatic benefit, but there are no data on safety and feasibility in this population. METHODS: A two-week, randomized, double blind, crossover phase Ib study was performed in advPD patients to compare standard-of-care (SoC) carbidopa/levodopa with PF-06412562, a selective D(1)/D(5) dopamine receptor partial agonist. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25+20 mg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers. RESULTS: Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22 y). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n=1, SoC: n=0), moderate (PF-06412562: n=1, SoC: n=1), or severe but non-serious (PF-06412562: n=3, SoC: n=2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians’ and four participants per caregivers’ rating. CONCLUSIONS: PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs. TRIAL REGISTRATION#: ClinicalTrials.gov:NCT03665454

Introduction: Commensurate with studies in middle-aged adults, we have previously shown that a cumulative exposure to sleep disordered breathing (SDB) since childhood is associated, independent of obesity, with endothelial dysfunction in young adulthood. There is a lack of population-based studies that have examined the association of SDB with atherosclerosis using such a developmental approach. Hypothesis: Exposure to SDB since childhood is associated with long-term increased carotid intima-media thickness (CIMT) in young adulthood. Methods: We tested this hypothesis in a subsample of the Penn State Child Cohort, a population-based study of 700 children (median age 9y), of whom 421 were followed-up 7.4 years later during adolescence (median age 16y), and 204 have been followed-up 15.4 years later during young adulthood (median age 24y). Subjects (53% female, 23% racial/ethnic minority) underwent in-lab polysomnography to ascertain the apnea/hypopnea index (AHI) at all three time points, and ultrasound to assess CIMT in young adulthood. Based on the AHI truncated at ≥5 events/hour of sleep to include subjects already on positive airway pressure therapy, we averaged the exposure to AHI over the three time points (cAHI). The study outcome was total CIMT from right and left carotids as a continuous measure. Stepwise linear regression models first adjusted for sex, age, race/ethnicity, and length of follow-up and, thereafter, for body mass index (BMI). To test the robustness of the analysis, we applied the same linear models with the square root of CIMT (sqrt-CIMT) as the outcome. Results: The mean cAHI was 1.16 (standard deviation=0.99) ranging from 0 to 5 and the mean CIMT was 0.51 (0.07) ranging from 0.37 to 0.79. Although cAHI was positively associated with higher CIMT in young adulthood (β = 0.015; 95% CI = 0.005, 0.025; p = 0.003), the association was significantly diminished after further adjusting for BMI (β = 0.004; 95% CI = -0.004, 0.014; p = 0.424). The results were similar when using sqrt-CIMT (β = 0.010; 95% CI = 0.004, 0.017; p = 0.002 before BMI adjustment; β = 0.003; 95% CI = -0.004, 0.010; p = 0.415 after BMI adjustment). Conclusions: In contrast to endothelial dysfunction, the preliminary data of this ongoing longitudinal study indicates that obesity plays a key role in the association between SDB and atherosclerosis in young adulthood.