Role of Blood Pressure Responses to Exercise and Vascular Insulin Sensitivity with Nocturnal Blood Pressure Dipping in Metabolic Syndrome.

INTRODUCTION: Nocturnal systolic blood pressure (SBP) dipping is independently related to cardiovascular disease risk, but it is unclear if vascular insulin sensitivity associates with SBP dipping in patients with metabolic syndrome (MetS). METHODS: Eighteen adults with MetS (ATP III criteria 3.3 ± 0.6; 53.2 ± 6.5 years; body mass index 35.8 ± 4.5 kg/m2) were categorized as "dippers" (≥10% change in SBP; n = 4 F/3 M) or "non-dippers" (<10%; n = 9 F/2 M). Twenty-four-hour ambulatory blood pressure was recorded to assess SBP dipping. A euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) with ultrasound (flow mediated dilation) was performed to test vascular insulin sensitivity. A graded, incremental exercise test was conducted to estimate sympathetic activity. Heart rate (HR) recovery after exercise was then used to determine parasympathetic activity. Metabolic panels and body composition (DXA) were also tested. RESULTS: Dippers had greater drops in SBP (16.63 ± 5.2 vs. 1.83 ± 5.6%, p < 0.01) and experienced an attenuated rise in both SBPslope (4.7 ± 2.3 vs. 7.2 ± 2.5 mm Hg/min, p = 0.05) and HRslope to the incremental exercise test compared to non-dippers (6.5 ± 0.9 vs. 8.2 ± 1.7 bpm/min, p = 0.03). SBP dipping correlated with higher insulin-stimulated flow-mediated dilation (r = 0.52, p = 0.03), although the relationship was no longer significant after covarying for HRslope (r = 0.42, p = 0.09). CONCLUSION: Attenuated rises in blood pressure and HR to exercise appear to play a larger role than vascular insulin sensitivity in SBP dipping in adults with MetS.

Randomized controlled trial to enhance children's sleep, eating, and weight.

BACKGROUND: The present study assessed the efficacy of a behavioral intervention to enhance children's sleep and reduce caloric intake and body mass index (BMI) change. METHODS: Seventy-eight children 8-11 years old who slept 9.5 h/night or less were randomized to the sleep intervention or to no treatment control. The primary outcome was 2-month change in the actigraph-estimated sleep period; changes in reported caloric intake, percent calories from fat, and BMI/BMI z-score (BMIz) were assessed. RESULTS: Children randomized to intervention enhanced their sleep period by 40 ± 7 min/night relative to control (p < 0.001), and were more likely to increase their sleep period by 30 min/night or more (52% versus 15%, p = 0.003). No differences were observed for reported dietary intake or BMI/BMIz. However, in post-hoc analyses collapsing across groups, those who increased sleep by 30 min/night or more had lower BMI (-0.31 kg/m2, p = 0.01) and BMIz (-0.07, p = 0.03) and reported fewer percent calories from fat at 2 months (-2.2%, p = 0.04). CONCLUSIONS: A brief behavioral intervention can enhance children's sleep, but did not result in changes in caloric intake or weight status. Enhancing sleep by 30 min/night or more may be beneficial for weight regulation. IMPACT: A brief behavioral intervention improved children's nocturnal sleep relative to no treatment control. Given the many benefits of a good night's sleep across domains of functioning, findings have significant implications for children's health and wellbeing. There were no differences between groups on eating behaviors or BMI. However, across groups, children who increased their sleep period by at least 30 min/night, reported reduced intake from fat and evidenced lower BMI at 2 months. Thus, a brief intervention can improve sleep and may have potential benefits for weight regulation.

Test-retest reliability of cerebral blood flow for assessing brain function at rest and during a vigilance task.

Arterial spin labeled (ASL) perfusion magnetic resonance imaging (MRI) is increasingly used to assess regional brain activity and cerebrovascular function in both healthy and clinical populations. ASL perfusion imaging provides a quantitative measure of regional brain activity by determining absolute cerebral blood flow (CBF) values at a resting state or during task performance. However, the comparative reliability of these ASL measures is not well characterized. It is also unclear whether the test-retest reliability of absolute CBF or task-induced CBF change measures would be comparable to the reliability of task performance. In this study, fifteen healthy participants were scanned three times in a strictly controlled in-laboratory study while at rest and during performing a simple and reliable psychomotor vigilance test (PVT). The reliability of absolute CBF and task-induced CBF changes was evaluated using the intraclass correlation coefficient (ICC) and compared to that of task performance. Absolute CBF showed excellent test-retest reliability across the three scans for both resting and PVT scans. The reliability of regional absolute CBF was comparable to that of behavioral measures of PVT performance, and was slightly higher during PVT scans as compared with resting scans. Task-induced regional CBF changes demonstrated only poor to moderate reliability across three scans. These findings suggest that absolute CBF measures are more reliable than task-induced CBF changes for characterizing regional brain function, especially for longitudinal and clinical studies.

Sleep and Eating Disorders.

Insomnia is related to an increased risk of eating disorders, while eating disorders are related to more disrupted sleep. Insomnia is also linked to poorer treatment outcomes for eating disorders. However, over the last decade, studies examining sleep and eating disorders have relied on surveys, with no objective measures of sleep for anorexia nervosa or bulimia nervosa, and only actigraphy data for binge eating disorder. Sleep disturbance is better defined for night eating syndrome, where sleep efficiency is reduced and melatonin release is delayed. Studies that include objectively measured sleep and metabolic parameters combined with psychiatric comorbidity data would help identify under what circumstances eating disorders and sleep disturbance produce an additive effect for symptom severity and for whom poor sleep would increase risk for an eating disorder. Cognitive behavior therapy for insomnia may be a helpful addition to treatment of those with both eating disorder and insomnia.

Resting spontaneous activity in the default mode network predicts performance decline during prolonged attention workload.

After continuous and prolonged cognitive workload, people typically show reduced behavioral performance and increased feelings of fatigue, which are known as "time-on-task (TOT) effects". Although TOT effects are pervasive in modern life, their underlying neural mechanisms remain elusive. In this study, we induced TOT effects by administering a 20-min continuous psychomotor vigilance test (PVT) to a group of 16 healthy adults and used resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine spontaneous brain activity changes associated with fatigue and performance. Behaviorally, subjects displayed robust TOT effects, as reflected by increasingly slower reaction times as the test progressed and higher self-reported mental fatigue ratings after the 20-min PVT. Compared to pre-test measurements, subjects exhibited reduced amplitudes of low-frequency fluctuation (ALFF) in the default mode network (DMN) and increased ALFF in the thalamus after the test. Subjects also exhibited reduced anti-correlations between the posterior cingulate cortex (PCC) and right middle prefrontal cortex after the test. Moreover, pre-test resting ALFF in the PCC and medial prefrontal cortex (MePFC) predicted subjects' subsequent performance decline; individuals with higher ALFF in these regions exhibited more stable reaction times throughout the 20-min PVT. These results support the important role of both task-positive and task-negative networks in mediating TOT effects and suggest that spontaneous activity measured by resting-state BOLD fMRI may be a marker of mental fatigue.

Behavioral Intervention that Extends Sleep Duration Leads to Greater Self-Control in School-Aged Children.

OBJECTIVE: Short sleep and evening phase preference associate with impaired self-control, yet few studies have assessed the efficacy of sleep extension for improving this behavioral domain. Thus, this secondary analysis of a behavioral sleep intervention measured whether an intervention that enhanced children's sleep also affected self-control. Differences by chronotype were also explored. METHODS: Sixty-seven children (8-11 yr), who reportedly slept <9.5 hr/d, were randomized to either a control or sleep intervention condition (i.e., 4-session behavioral intervention to enhance sleep by 1-1.5 hr/night). Chronotype was assessed using the Child Chronotype Questionnaire at baseline, and self-control was assessed using the Self-Control Rating Scale (SCRS, a caregiver report) at baseline and 8 weeks postrandomization. Total sleep time (TST) was measured using wrist actigraphy for 1 week at both baseline and 8 weeks postrandomization. Partial correlations and mixed-model ANOVAs were used for statistical analyses, with age as a covariate. RESULTS: At baseline, children with shorter TST (r = -0.29, p = 0.02) and an evening preference (r = 0.26, p = 0.049) were perceived as having lower self-control by their caregivers. Significant condition*time interaction effects were found for TST (p < 0.001) and SCRS score (p = 0.046): From baseline to follow-up, children randomized to the sleep intervention exhibited a significant increase in TST and were perceived as having greater self-control by their caregiver; children randomized to the control condition exhibited no change in TST or in SCRS score. The condition*chronotype*time interaction effect was not significant. CONCLUSION: A brief sleep intervention that enhanced TST also resulted in enhanced caregiver reported self-control in school-age children. Results add to the growing evidence for the importance of sleep health in children.

The Role of Meeting Exercise and Nutrition Guidelines on Sleep during Pregnancy.

Sleep disturbances are common during pregnancy. This study determined whether meeting physical activity or dietary guidelines during pregnancy was associated with improved sleep. Third trimester pregnant women (n = 49, 31.9 ± 4.1 years) completed physical activity and sleep questionnaires and then wore a wrist actigraph 24 h/day and completed three 24 h dietary recalls across two weeks. Participants who reported meeting physical activity guidelines (>150 min moderate-to-vigorous physical activity [MVPA]/week, n = 23) or dietary guidelines (≥1.1 g protein/kg body weight/day, n = 26 or ≥25 g fiber/day, n = 16) were compared to those who were physically inactive (<90 min/week) or did not meet dietary guidelines, respectively. Multivariate ANOVAs and Mann-Whitney U tests compared groups and correlations were conducted between physical activity, diet, and sleep variables. Physical activity groups did not differ in objective sleep measures (ps > 0.05); however, the active group reported better sleep quality (p = 0.049). Those who met protein guidelines exhibited longer sleep duration and less wake-after-sleep-onset (ps < 0.05). Across all participants, higher weekly MET mins/week of MVPA associated with better sleep quality (p = 0.02), and a diet higher in fat and lower in carbohydrates associated with longer sleep duration (ps < 0.05). Meeting physical activity and nutrition guidelines positively associates with improved sleep, with protein associated with objective measures and physical activity with subjective measures.

Dose-dependent Relationships of Same-day and Typical Substance Use to Sleep Duration in College Cannabis and Alcohol Users: A Multilevel Modeling Approach Using Daily Diary Data.

This study characterized how quantities of cannabis and alcohol use affect sleep. Single-day and typical cannabis and alcohol use patterns were considered to assess acute-chronic use interactions. Linear and non-linear associations assessed dose-dependence. College students (n=337; 52% female) provided 11,417 days of data, with up to five time points per day. Daily self-reported sleep duration, cannabis use quantity, and alcohol use quantity were subjected to linear mixed modeling to capture linear and curvilinear associations between single-day and typical use on same-night and typical sleep. Sleep duration (difference between bedtime and waketime) was the outcome. Quantity of cannabis used each day andtypical quantity used across all days were predictors in the cannabis models. Parallel single-day and typical alcohol variables were predictors in the alcohol models. Follow-up analyses excluded days with alcohol-cannabis co-use. Main effects of single-day and typical cannabis quantity on sleep duration were observed when all cannabis-use days were modeled. Higher than typical doses of single-day and typical cannabis were associated with longer sleep durations, but only to a point; at the highest doses, cannabis shortened sleep. A main effect of single-day alcohol quantity and two interactions (single-day use with both linear and curvilinear typical use) on sleep duration were observed when all alcohol-use days were modeled. Greater alcohol consumption on a given day led to shorter same-night sleep, but typically heavier drinkers required higher doses than typically lighter drinkers to experience these adverse effects. Follow-up models suggested alcohol co-use may contribute to the purported sleep-promoting effects of cannabis.

Pediatric sleep: current knowledge, gaps, and opportunities for the future.

This White Paper addresses the current gaps in knowledge, as well as opportunities for future studies in pediatric sleep. The Sleep Research Society's Pipeline Development Committee assembled a panel of experts tasked to provide information to those interested in learning more about the field of pediatric sleep, including trainees. We cover the scope of pediatric sleep, including epidemiological studies and the development of sleep and circadian rhythms in early childhood and adolescence. Additionally, we discuss current knowledge of insufficient sleep and circadian disruption, addressing the neuropsychological impact (affective functioning) and cardiometabolic consequences. A significant portion of this White Paper explores pediatric sleep disorders (including circadian rhythm disorders, insomnia, restless leg and periodic limb movement disorder, narcolepsy, and sleep apnea), as well as sleep and neurodevelopment disorders (e.g. autism and attention deficit hyperactivity disorder). Finally, we end with a discussion on sleep and public health policy. Although we have made strides in our knowledge of pediatric sleep, it is imperative that we address the gaps to the best of our knowledge and the pitfalls of our methodologies. For example, more work needs to be done to assess pediatric sleep using objective methodologies (i.e. actigraphy and polysomnography), to explore sleep disparities, to improve accessibility to evidence-based treatments, and to identify potential risks and protective markers of disorders in children. Expanding trainee exposure to pediatric sleep and elucidating future directions for study will significantly improve the future of the field.

TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin.

Brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling contribute to the central nervous system (CNS) control of energy balance. The role of hindbrain BDNF/TrkB receptor signaling in energy balance regulation is examined here. Hindbrain ventricular BDNF suppressed body weight through reductions in overall food intake and meal size and by increasing core temperature. To localize the neurons mediating the energy balance effects of hindbrain ventricle-delivered BDNF, ventricle subthreshold doses were delivered directly to medial nucleus tractus solitarius (mNTS). mNTS BDNF administration reduced food intake significantly, and this effect was blocked by preadministration of a highly selective TrkB receptor antagonist {[N2-2-2-Oxoazepan-3-yl amino]carbonyl phenyl benzo (b)thiophene-2-carboxamide (ANA-12)}, suggesting that TrkB receptor activation mediates hindbrain BDNF's effect on food intake. Because both BDNF and leptin interact with melanocortin signaling to reduce food intake, we also examined whether the intake inhibitory effects of hindbrain leptin involve hindbrain-specific BDNF/TrkB activation. BDNF protein content within the dorsal vagal complex of the hindbrain was increased significantly by hindbrain leptin delivery. To assess if BDNF/TrkB receptor signaling acts downstream of leptin signaling in the control of energy balance, leptin and ANA-12 were coadministered into the mNTS. Administration of the TrkB receptor antagonist attenuated the intake-suppressive effects of leptin, suggesting that mNTS TrkB receptor activation contributes to the mediation of the anorexigenic effects of hindbrain leptin. Collectively, these results indicate that TrkB-mediated signaling in the mNTS negatively regulates food intake and, in part, the intake inhibitory effects of leptin administered into the NTS.

To eat or not to eat red meat. A closer look at the relationship between restrained eating and vegetarianism in college females.

Previous research has suggested that vegetarianism may serve as a mask for restrained eating. The purpose of this study was to compare the dietary habits and lifestyle behaviors of vegetarians (n=55), pesco-vegetarians (n=28), semi-vegetarians (n=29), and flexitarians (n=37), to omnivores (n=91), who do not restrict animal products from their diets. A convenience sample of college-age females completed questionnaires about their eating habits, food choice motivations, and personality characteristics. Results indicated that while vegetarians and pesco-vegetarians were more open to new experiences and less food neophobic, they were not more restrained than omnivores. Rather semi-vegetarians; those who restricted only red meat from their diet, and flexitarians; those who occasionally eat red meat, were significantly more restrained than omnivores. Whereas food choices of semi-vegetarians and flexitarians were motivated by weight control, vegetarians and pesco-vegetarians' food choices were motivated by ethical concerns. By focusing specifically on semi-vegetarian and flexitarian subgroups, more effective approaches can be developed to ensure that their concerns about weight loss do not lead to unhealthful or disordered eating patterns.

Gender Differences in the Relationship Between Exercise, Sleep, and Mood in Young Adults.

Insufficient sleep is a serious public health problem in college students. Exercise is a widely prescribed behavioral treatment for sleep and mood issues; however, more focused and gender-specific prescriptions are needed. The present study examined relationships between exercise, sleep, and mood in undergraduate men and women. Students (N = 866, 19.6 ± 1.4 years, 38.7% women) were recruited from campus recreation facilities and completed demographic, the Pittsburgh Sleep Quality Index, mood (Patient-Reported Outcomes Measurement Information System), and exercise questionnaires. The Department of Health and Human Services Physical Activity Guidelines were used to dichotomize those who did and did not meet weekly aerobic and strength training exercise recommendations. In men, greater exercise frequency associated with less daytime dysfunction (ß = 0.147) and less depressive mood (ß = -0.64, ps < .05). In women, greater exercise frequency associated with earlier bedtime (ß = -12.6), improved sleep quality (ß = 0.17), increased positive affect (ß = 0.91), less depressive mood (ß = -0.71), and less anger (ß = -1.24, ps < .05). Compared to men, women reported earlier bedtime, poorer sleep efficiency, and more anxiety and depressive mood (ps < .05, ηp2 range: 0.01-0.04). Compared to individuals who met physical activity guidelines, those who did not meet the guidelines reported later bedtimes, less positive affect, more anxiety, and more anger (ps < .05 ηp2s = 0.01). Among men, those who met physical activity guidelines reported falling asleep more quickly than those who did not meet guidelines (ηp2 = 0.01, p = .007); however, no relationship between guideline adherence and sleep latency was observed in women. Adhering to physical activity guidelines may be important for optimal sleep and emotional health. Clinicians should consider gender when creating exercise prescriptions for sleep issues.

Insulin Sensitivity and Metabolic Flexibility Parallel Plasma TCA Levels in Early Chronotype With Metabolic Syndrome.

CONTEXT: People characterized as late chronotype have elevated type 2 diabetes and cardiovascular disease risk compared to early chronotype. It is unclear how chronotype is associated with insulin sensitivity, metabolic flexibility, or plasma TCA cycle intermediates concentration, amino acids (AA), and/or beta-oxidation. OBJECTIVE: This study examined these metabolic associations with chronotype. METHODS: The Morningness-Eveningness Questionnaire (MEQ) was used to classify adults with metabolic syndrome (ATP III criteria) as either early (n = 15 [13F], MEQ = 64.7 ±â€…1.4) or late (n = 19 [16F], MEQ = 45.5 ±â€…1.3) chronotype. Fasting bloods determined hepatic (HOMA-IR) and adipose insulin resistance (Adipose-IR) while a 120-minute euglycemic clamp (40 mU/m2/min, 5 mmoL/L) was performed to test peripheral insulin sensitivity (glucose infusion rate). Carbohydrate (CHOOX) and fat oxidation (FOX), as well as nonoxidative glucose disposal (NOGD), were also estimated (indirect calorimetry). Plasma tricarboxylic acid cycle (TCA) intermediates, AA, and acyl-carnitines were measured along with VO2max and body composition (DXA). RESULTS: There were no statistical differences in age, BMI, fat-free mass, VO2max, or ATP III criteria between groups. Early chronotype, however, had higher peripheral insulin sensitivity (P = 0.009) and lower HOMA-IR (P = 0.02) and Adipose-IR (P = 0.05) compared with late chronotype. Further, early chronotype had higher NOGD (P = 0.008) and greater insulin-stimulated CHOOX (P = 0.02). While fasting lactate (P = 0.01), TCA intermediates (isocitrate, α-ketoglutarate, succinate, fumarate, malate; all P ≤ 0.04) and some AA (proline, isoleucine; P = 0.003-0.05) were lower in early chronotype, other AA (threonine, histidine, arginine; all P ≤ 0.05) and most acyl-carnitines were higher (P ≤ 0.05) compared with late chronotype. CONCLUSION: Greater insulin sensitivity and metabolic flexibility relates to plasma TCA concentration in early chronotype.

Effect of changes in children's bedtime and sleep period on targeted eating behaviors and timing of caloric intake.

Short sleep is associated with obesity risk. Experimental studies with adults and observational studies with children demonstrate that changes in eating, including increased caloric intake from energy-dense foods and sugar-sweetened beverages as well as increased caloric intake in the evening, may partially account for this increased risk. We therefore examined whether experimental changes in children's sleep period lead to changes in reported caloric intake from energy-dense snack foods and sugar-sweetened beverages, and in the evening. Thirty-seven children, 8-11 years old, completed a three-week study that used a within-subject randomized cross-over design. Children slept their typical amount for one week and were subsequently randomized to either increase or decrease their typical amount by 1.5 h/night for one week; the alternate schedule was completed during the third week of the study, creating a 3-h time in bed difference between the increase and decrease conditions. Sleep was monitored with actigraphy, and dietary intake was assessed with 24-hour dietary recalls. Participants reported consuming 35 kcal per day more from sugar-sweetened beverages during the decrease sleep than the increase sleep condition, p = .033. There were no reported differences between conditions from energy-dense snack foods. Although no differences in reported intake were observed earlier in the day, from 2000 h (8:00 PM) and later, children reported consuming 132 kcal more during the decrease sleep condition than the increase condition, p < 0.001. Shortened sleep achieved by delaying bedtimes led to increased caloric intake in the evening and from sugar-sweetened beverages. Clinical Trials Registration: clinicaltrials.gov Identifier: NCT01030107.

Determinants of postpartum sleep duration and sleep efficiency in minority women.

STUDY OBJECTIVES: To examine demographic, psychosocial, and behavioral determinants of postpartum sleep duration and sleep efficiency among a cohort of black and Latina women. METHODS: Data were from 148 women (67% black, 32% Latina) at 5 months postpartum, recruited from an academic medical center in Philadelphia. Relevant demographic, psychosocial and behavioral predictors were assessed via questionnaire. Nocturnal sleep was objectively measured for 1 week using wrist actigraphy. Sleep duration was examined as a continuous variable and in categories (<7 versus ≥7 h per night); sleep efficiency was examined as a continuous variable. Independent multiple linear regression models were built to evaluate significant determinants of sleep. RESULTS: Adjusted models revealed that breastfeeding, having a bedtime after midnight, and being employed were associated with shorter sleep duration (-25-33 min, all p < 0.05). Multiparity, being unmarried, being employed, breastfeeding, having a bedtime after midnight, bedsharing, and responding to infant awakenings by getting up immediately rather than waiting a few minutes to see if the infant fell back asleep, were all significant determinants of sleeping <7 h per night (OR varying: 2.29-4.59, all p < 0.05). Bedsharing was the only variable identified from the multiple regression model that associated with poorer sleep efficiency (-3.8%, p < 0.05). CONCLUSIONS: Findings may inform interventions for improving postpartum sleep in socioeconomically disadvantaged, racial/ethnic minority postpartum women.

Considerations for Maximizing the Exercise "Drug" to Combat Insulin Resistance: Role of Nutrition, Sleep, and Alcohol.

Insulin resistance is a key etiological factor in promoting not only type 2 diabetes mellitus but also cardiovascular disease (CVD). Exercise is a first-line therapy for combating chronic disease by improving insulin action through, in part, reducing hepatic glucose production and lipolysis as well as increasing skeletal muscle glucose uptake and vasodilation. Just like a pharmaceutical agent, exercise can be viewed as a "drug" such that identifying an optimal prescription requires a determination of mode, intensity, and timing as well as consideration of how much exercise is done relative to sitting for prolonged periods (e.g., desk job at work). Furthermore, proximal nutrition (nutrient timing, carbohydrate intake, etc.), sleep (or lack thereof), as well as alcohol consumption are likely important considerations for enhancing adaptations to exercise. Thus, identifying the maximal exercise "drug" for reducing insulin resistance will require a multi-health behavior approach to optimize type 2 diabetes and CVD care.

Relationships between sleep, exercise timing, and chronotype in young adults.

To examine the relationships between exercise timing, chronotype, sleep, and mood, college students (N = 909, 19.6 ± 1.4 years, 38% female) completed questionnaires immediately after exercising. Evening exercisers had later bedtimes, poorer sleep quality, and lower sleep efficiency compared to morning exercisers. Evening chronotypes reported poorer sleep quality, greater daytime dysfunction, and less positive affect compared to morning/neither chronotypes. Chronotype moderated the relationship between exercise timing and bedtime; with each minute delay in exercise timing, bedtime was delayed by 6.1 minutes in morning-types and only 3.6 minutes in evening-types. University health initiatives should target evening exercisers to mitigate the consequences of prolonged insufficient sleep.

The Insomnia-Addiction Positive Feedback Loop: Role of the Orexin System.

Significant sleep impairments often accompany substance use disorders (SUDs). Sleep disturbances in SUD patients are associated with poor clinical outcomes and treatment adherence, emphasizing the importance of normalizing sleep when treating SUDs. Orexins (hypocretins) are neuropeptides exclusively produced by neurons in the posterior hypothalamus that regulate various behavioral and physiological processes, including sleep-wakefulness and motivated drug taking. Given its dual role in sleep and addiction, the orexin system represents a promising therapeutic target for treating SUDs and their comorbid sleep deficits. Here, we review the literature on the role of the orexin system in sleep and drug addiction and discuss the therapeutic potential of orexin receptor antagonists for SUDs. We argue that orexin receptor antagonists may be effective therapeutics for treating addiction because they target orexin's regulation of sleep (top-down) and motivation (bottom-up) pathways.

Prolonged, Controlled Daytime versus Delayed Eating Impacts Weight and Metabolism.

A delayed eating schedule is associated with increased risk of obesity and metabolic dysfunction in humans.1-9 However, there are no prolonged, highly controlled experimental studies testing the effects of meal timing on weight and metabolism in adults with a body mass index (BMI) of 19-27 kg/m2.10-18 Twelve healthy adults (age: 26.3 ± 3.4 years; BMI: 21.9 ± 1.7 kg/m2; 5 females) participated in a randomized crossover study in free-living conditions. Three meals and two snacks with comparable energy and macronutrient contents were provided during two, 8-week, counterbalanced conditions separated by a 2-week washout period: (1) daytime (intake limited to 0800 h-1900 h) and (2) delayed (intake limited to 1200 h-2300 h). Sleep-wake cycles and exercise levels were held constant. Weight, adiposity, energy expenditure, and circadian profiles of hormones and metabolites were assessed during four inpatient visits occurring before and after each condition. Body weight, insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]), trunk-to-leg fat ratio, resting energy expenditure, respiratory quotient, and fasting glucose, insulin, total and high-density lipoprotein (dHDL) cholesterol, and adiponectin decreased on the daytime compared to the delayed schedule. These measures, as well as triglycerides, increased on the delayed compared to the daytime schedule (effect size range: d = 0.397-1.019). Circadian phase and amplitude of melatonin, cortisol, ghrelin, leptin, and glucose were not differentially altered by the eating schedules. Overall, an 8-week daytime eating schedule, compared to a delayed eating schedule, promotes weight loss and improvements in energy metabolism and insulin in adults with BMI 19-27 kg/m2, underscoring the efficacy and feasibility of daytime eating as a behavioral modification for real-world conditions.

Caloric and Macronutrient Intake and Meal Timing Responses to Repeated Sleep Restriction Exposures Separated by Varying Intervening Recovery Nights in Healthy Adults.

Sleep restriction (SR) reliably increases caloric intake. It remains unknown whether such intake cumulatively increases with repeated SR exposures and is impacted by the number of intervening recovery sleep opportunities. Healthy adults (33.9 ± 8.9y; 17 women, Body Mass Index: 24.8 ± 3.6) participated in a laboratory protocol. N = 35 participants experienced two baseline nights (10 h time-in-bed (TIB)/night; 22:00-08:00) followed by 10 SR nights (4 h TIB/night; 04:00-08:00), which were divided into two exposures of five nights each and separated by one (n = 13), three (n = 12), or five (n = 10) recovery nights (12 h TIB/night; 22:00-10:00). Control participants (n = 10) were permitted 10 h TIB (22:00-08:00) on all nights. Food and drink consumption were ad libitum and recorded daily. Compared to baseline, sleep-restricted participants increased daily caloric (+527 kcal) and saturated fat (+7 g) intake and decreased protein (-1.2% kcal) intake during both SR exposures; however, intake did not differ between exposures or recovery conditions. Similarly, although sleep-restricted participants exhibited substantial late-night caloric intake (671 kcal), such intake did not differ between exposures or recovery conditions. By contrast, control participants showed no changes in caloric intake across days. We found consistent caloric and macronutrient intake increases during two SR exposures despite varying intervening recovery nights. Thus, energy intake outcomes do not cumulatively increase with repeated restriction and are unaffected by recovery opportunities.