bluuebunny/crossref_metadata_2025_split huggingface dataset:
0151 The Dual Orexin Receptor Antagonist Almorexant Blocks the Sleep-Disrupting Effects of Methamphetamine in Male Rhesus Monkeys
Authors: Berro L F , Rowlett J K 
Published: May 2020

Abstract

Introduction
Individuals with stimulant use disorder show a high prevalence of sleep problems. In the laboratory, stimulant drugs have been shown to affect sleep parameters in human and nonhuman primates, even when administered many hours before bedtime. Although the mechanisms underlying the relationship between stimulant use/abuse and sleep impairment remain unclear, recent research has implicated the orexin (also called “hypocretin”) system as a critical regulator of sleep-wake states. The aim of the present study was to investigate the effects of the dual orexin receptor antagonist (DORA) almorexant on the sleep-disrupting effects of methamphetamine in rhesus monkeys.

Methods
Male adult rhesus monkeys (Macaca mulatta, n=4) were fitted with primate collars to which Actiwatch monitors were attached. Actigraphy recording was conducted during baseline conditions and on the night after acute morning (9h) administration of vehicle or methamphetamine (0.03, 0.1 or 0.3 mg/kg, i.m.). During a second set of treatments, vehicle or almorexant (1, 3 or 10 mg/kg, i.m.) were administered in the evening (16:30h, 1.5h before “lights off”) following morning (9h) administration of methamphetamine (0.3 mg/kg, i.m.).

Results
Morning methamphetamine administration dose-dependently impaired sleep in rhesus monkeys, with the dose of 0.3 mg/kg significantly increasing sleep latency and decreasing sleep efficiency. Evening administration of almorexant improved both actigraphy-based sleep measures after morning administration of methamphetamine in a dose dependent manner.

Conclusion
Our findings indicate that orexin receptor systems are involved in methamphetamine-induced sleep disruption. The exact role of the two orexin receptors in this effect, alone or together, remains to be determined. This study suggests that DORAs can be effective in treating sleep impairment in individuals with methamphetamine use disorder or under stimulant prescription for other sleep and psychiatric disorders.

Support
Supported by UMMC Research Enhancement Funds.
0160 Chemogenetic Activation of Hypothalamic Tachykinin 1-Expressing Neurons Reduces Sleep and Increases Resistance to Isoflurane
Authors: Reitz S , Wasilczuk A Z , Beh G , Kelz M B 
Published: May 2020

Abstract

Introduction
The hypothalamic preoptic area (POA) is a heterogeneous region of the brain, containing intermingled populations of excitatory and inhibitory neurons expressing a wide variety of molecular markers. Of its many important homeostatic roles, the POA modulates arousal including natural states (sleep and wakefulness) as well as drug-induced (anesthetic-induced unconsciousness) states. Although sleep and anesthetic-induced unconsciousness are undoubtedly distinct, multiple lines of evidence demonstrate that shared neuronal circuits regulate both states. Previous work identified a population of sleep-promoting, tachykinin 1-expressing (Tac1) neurons within the POA. Given evidence in the VLPO and SON, we hypothesized that Tac1 POA neurons would be another site of convergence for facilitating entry into both NREM sleep and anesthetic-induced unconsciousness.

Methods
Sleep and isoflurane sensitivity were assessed in Tac1-Cre mice expressing either a Cre-dependent excitatory hM3Dq DREADD or a control fluorophore in the POA. Sleep was assessed using beam break actigraphy, while isoflurane sensitivity was assessed using video tracking as well as a loss of righting reflex assay to construct dose-response curves.

Results
Unexpectedly, activation of Tac1 POA neurons with 3mg/kg CNO reduced cumulative sleep time by 55% compared to controls (p&lt;0.0001). Decreased sleep time was due to a 59% reduction in sleep bout duration (p&lt;0.01), as the number of sleep bouts remained unchanged. Activity, measured as distance traveled, also increased by 167% compared to vehicle (p&lt;0.0001). Activation of these neurons also increased resistance to isoflurane on both induction (p&lt;0.0001) and emergence (p&lt;0.0001). Additionally, activation during a continuous steady-state exposure to isoflurane destabilized the unconscious state.

Conclusion
Our results support the concept that POA Tac1 neurons function as a point of convergence for neural circuits regulating arousal from endogenous and drug-induced states of unconsciousness, while also illustrating the complexity of sleep and wake regulation within the hypothalamus.

Support
R01-GM088156-06, T32-HL007953
0165 The Relationship Between Anxiety Symptoms and Sleep Quality: Mediating and Moderating Factors of Pre-Sleep Arousal and Anxiety Sensitivity
Authors: Nagy S , Pickett S M , Hedge M , Mesa J , Mechal R 
Published: May 2020

Abstract

Introduction
The relationship between anxiety and sleep has been well-established, with many studies demonstrating the relationship between anxiety and reduced REM time, increased sleep latency, and reduced sleep efficiency. Anxiety sensitivity, or the fear of experiencing anxiety-related sensations, has also been associated with increased sleep latency and sleep dysfunction. This delay in sleep onset may be explained by increased arousal, both physical and cognitive, immediately before sleep related to worry or anxiety. The current study examined the relationship between anxiety and subjective sleep quality through pre-sleep arousal and investigated the moderating effect of anxiety sensitivity.

Methods
Participants (n=322) were recruited from Amazon’s MTurk site, with most identifying as female (58.5%) and White/Caucasian (84.4%) and with an average age of 37.51 (SD = 12.12). Participants completed the Daily Assessment of Symptoms - Anxiety Scale (DAS-A), the Anxiety Sensitivity Index (ASI), the Pre-Sleep Arousal Scale (PSAS) and the Pittsburg Sleep Quality Index (PSQI). A moderated mediation analysis was conducted using Model 58 in PROCESS for SPSS.

Results
Results indicated that pre-sleep arousal partially mediated the relationship between anxiety and the dichotomous sleep quality variable while controlling for the covariates of age, and therapy participation, (a1= .186, p&lt;.001, b1= .113, p&lt;.001, c’= .038, p&lt;.001). Additionally, the conditional effects and interactions of the moderating anxiety sensitivity variable were significant in both pathways (a1: F=24.702, p&lt;.001; b1: χ 2 = 5.255, p=0.22).

Conclusion
These results help to identify potential mechanisms and conditions of the relationship between anxiety and sleep quality and contribute to the development of evidence-based interventions for sleep disturbance or other sleep complaints in individuals experiencing anxiety and anxiety symptoms.

Support
N/A
0166 Sleep Inconsistency Related Changes in Brain Function During Task and Rest
Authors: Zhang R , Tomasi D , Shokri-Kojori E , Wiers C E , Wang G , Volkow N D 
Published: May 2020

Abstract

Introduction
Sleep deprivation and circadian disruptions impair brain function and cognitive performance, but few studies have examined the effect of sleep inconsistency. Here we investigated how inconsistent sleep duration and sleep timing between weekend (WE) and weekdays (WD) affected behavior and brain function during task and at rest in 56 (30 female) healthy human subjects.

Methods
WE-WD differences in sleep duration and sleep midpoint were calculated using one-week actigraphy data. All subjects underwent 3Tesla BOLD-fMRI to measure brain activity during a visual attention task (VAT) and in resting-state condition.

Results
We found that WE-WD inconsistency of sleep duration and sleep midpoint were uncorrelated with each other (r=.08, p=.58) and influenced behavior and brain function differently. Our healthy subjects showed relatively small WE-WD differences (WE-WD: 0.59 hours) and benefited from longer WE catch-up sleep, which was associated with better attentional performance (3-ball: β=.30, t=2.35, p = .023; 4-ball: β=.30, t=2.21, p =.032) and greater deactivation of the default mode network (DMN) during VAT (p &lt; .05, cluster-corrected) and greater resting-state functional connectivity (RSFC) between anterior DMN and occipital cortex (p &lt; .01, cluster-corrected). In contrast, inconsistent WE-WD sleep midpoint (WE-WD: 1.11 hours) was associated with worse performance (4-ball: β=-.33, t=-2.42, p = .020) and with lower occipital activation during VAT and lower RSFC within the DMN.

Conclusion
Our results document the importance of consistent sleep timing for brain function in particular of the DMN, and provide evidence of the benefits of WE catch-up sleep in healthy adults.

Support
This work was supported by NIAAA IRP (Y01AA3009). R.Z. received research fellowship from German research foundation (DFG).
0170 Association of HIF-1 Alpha and Beta Subunits with Clock and BMAL1 Proteins in Obstructive Sleep Apnea Patients
Authors: Gabryelska A , Sochal M , Turkiewicz S , Bialasiewicz P 
Published: May 2020

Abstract

Introduction
Obstructive sleep apnea (OSA) is a chronic condition that is characterized by intermittent hypoxia. Key regulator of oxygen metabolism is hypoxia inducible factor (HIF), which consists of oxygen sensitive subunit and continuously produced subunit. Circadian clock is composed of set of genes, which function as activators - CLOCK and BMAL 1, who similarly to HIF are basic helix-loop-helix-PER-ARNT-SIM transcription factors. Therefore, the aim of the study was to assess the relationship between HIF-1alpha, HIF-1beta, CLOCK, BMAL1 and polysomnography (PSG) variables in healthy individuals and severe OSA patients.

Methods
The study included 20 individuals, who underwent PSG and based on apnea-hypopnea index (AHI) were divided into severe OSA group (n=10; AHI30; 90% male) and healthy control (n=10; AHI&lt;5; 70% male). All participants had their peripheral blood collected in the evening (9:00-10:00 pm) before and in the morning (6:00-7:00 am) after the PSG. HIF-1alpha, HIF-1beta, CLOCK and BMAL1 protein concertation measurements were performed using ELISA.

Results
Significant difference was observed in the following protein measurements between study groups: evening and morning HIF-1 (p=0.020 and p=0.043, respectively), evening HIF-1alpha (p=0.047), evening and morning CLOCK (p=0.037 and p=0.019, respectively) and morning BMAL1 (p=0.016). No differences were observed between morning and evening protein levels in both groups. Evening HIF-1beta corraleted with evening CLOCK and morning BMAL1 (R=0.511, p=0.21 and R=0.594, p=0.006, respectively), while morning HIF-1 with evening BMAL1 (R=474, p=0.35). Furthermore, evening and morning HIF-1 correlated with evening BMAL1 (R=564, p=0.010 and R=0.689, p=0.001, respectively). Additionally, morning CLOCK and BMAL1 correlated with AHI (R=0.510, p=0.022 and R=0.560, p=0.010, respectively) and desaturation index (R=0.487, p=0.209 and R=0.570, p=0.009, respectively).

Conclusion
There is significant correlation between both subunits of HIF-1 protein and circadian clock proteins: CLOCK and BMAL1, which further correlate with increased disease severity. This suggests OSA patients are in risk of circadian clock disruption due to present hypoxia.

Support
The study was financed by Polish National Centre Grant no. 2018/31/N/NZ5/03931.
0178 The Cycle of Daily Stress and Sleep: Sleep Measurement Matters
Authors: Slavish D C , Asbee J , Veeramachaneni K , Messman B , Scott B , Walker J , Sin N L , Taylor D J , Dietch J 
Published: May 2020

Abstract

Introduction
Disturbed sleep can be both a cause and a consequence of increased stress. Yet intensive longitudinal studies have demonstrated that sleep assessed via sleep diaries and actigraphy is inconsistently associated with daily stress. We expanded this research by examining daily associations between sleep and stress using a three-fold approach to assess sleep: sleep diaries, actigraphy, and ambulatory single-channel electroencephalography [EEG].

Methods
Participants were 80 adults (M age = 32.65 years, 63% female) who completed 7 days of sleep and perceived stress assessments in a naturalistic setting (resulting in 560 possible measurement occasions). Multilevel models were used to examine bidirectional associations between daily stressor occurrence (0 = stressor did not occur, 1 = stressor occurred) and stressor severity (0 = not at all severe to 3 = very severe) and sleep parameters assessed via diary, actigraphy, and EEG (e.g. total sleep time [TST], sleep efficiency [SE], and sleep onset latency [SOL], wake after sleep onset [WASO]).

Results
Participants reported at least one stressor on 37% of days. Compared to days without a stressor experienced, days with a stressor were associated with a 14.4-minute reduction in actigraphy-determined TST the subsequent night (β = -0.24, p = 0.030). Nights with greater sleep-diary determined WASO were associated with greater next-day stressor severity (β = 0.01, p = .026). No EEG-determined sleep parameters were associated with next-day stressor occurrence or severity, or vice versa.

Conclusion
Daily stress and sleep disturbances occurred in a bidirectional fashion, though specific results varied by sleep measurement technique and sleep parameter. Together, our results highlight that type of sleep measurement matters for examining associations with daily stress. We urge future researchers to treat sleep diaries, actigraphy, and EEG as complementary — not redundant — sleep measurement approaches.

Support
Funding for this study included NIH/NIAID R01AI128359-01; DoD-VA 1I01CU000144-01; the Foundation for Rehabilitation Psychology; and General Sleep Corporation.
0185 Sleep Behaviors and Thoughts as Links Between Social Rhythmicity and Depressive Symptoms
Authors: Sabet S M , Dautovich N D , Dzierzewski J M 
Published: May 2020

Abstract

Introduction
Disturbances in social circadian rhythms (e.g. regularity of meals and social interactions) and poor sleep are two potential factors that may contribute to the development of mood disorders. To date, no studies have investigated sleep behaviors (e.g. sleep health) and sleep thoughts (e.g. sleep self-efficacy) as potential links between social rhythmicity and mental health outcomes. The current study explored whether (1) higher social rhythmicity predicted fewer symptoms of depression and whether (2) sleep health and sleep self-efficacy act as mechanisms underlying this association.

Methods
An archival analysis was performed using data from an online study, Investigating Sleep Across Normal Development (ISLAND Study). The sample consisted of 4,261 adults aged 18+. Measures of social rhythmicity (SRM-10), sleep self-efficacy (SES), sleep health (RU SATED), and depressive symptoms (PHQ-2) were utilized. Age and gender were included as covariates in mediation analyses.

Results
The overall model was significant, p &lt; .0001 and 26.4% of the total variance was accounted for by social rhythmicity. Controlling for covariates, higher social rhythmicity was directly associated with fewer depressive symptoms (95% CI [.0326, .0420]). Additionally, both sleep health 95% CI [.0034, .0078] and sleep self-efficacy [.0119, .0169] significantly mediated the association between social rhythmicity and depressive symptoms.

Conclusion
Individuals who have higher levels of daily routine regularity experienced less depressive symptoms than those who are more irregular in their daily routines. Furthermore, individuals who had more regular lifestyle habits were more likely to engage in healthy sleep behaviors and thoughts. Thoughts and behaviors are common factors that may have an impact on mental health given their daily reoccurrence. Also, as these factors are modifiable they could be targeted to potentially reduce depressive symptoms. Future research should continue to examine the link between social rhythmicity and sleep behaviors and thoughts on various health outcomes.

Support
This work was supported by the National Institute on Aging (K23AG049955, PI: Dzierzewski).
0188 Mood Disorders Moderate the Relationship Between Sleep Quality and Leadership Development for U.S. Army Officer Candidates During ROTC Advanced Camp
Authors: Choynowski J , Pirner M , Mickelson C , Mantua J , Sowden W J , Burke T , Capaldi V F , McKeon A B 
Published: May 2020

Abstract

Introduction
U.S. Army Reserve Officer Training Corps (ROTC) Cadets are college students training to be Army Officers. During a month-long capstone course (Advanced Camp), Cadets are rated on their leadership ability. Little work has been done to determine predictors of leadership ability at Advanced Camp. This study examined the effect of poor sleep and mood disorders -- two prevalent factors among college students -- on leadership ability.

Methods
Metrics on leadership, sleep quality, anxiety, and depression, were assessed in 159 ROTC Cadets (22.06±2.49 years; 23.90%female) at Days 1 (Baseline), 14 (Mid), and 29 (Post) of Advanced Camp. Leadership ratings were determined by ROTC Instructors over the course of Advanced Camp (1–5 score; higher score indicates poorer leadership). Predictors were the Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-9. The relationships between the predictors and leadership scores were tested using linear regression. The interaction between mood disorders and sleep quality on leadership was tested using SPSS Process (Model 1).

Results
Poorer sleep quality at the Post time point (reflecting the prior 2 weeks of sleep) predicted poorer leadership (B=.05,p=.03), while sleep quality from Baseline (B=.03,p=.14) and Mid (B=.01,p=.67) did not. Higher anxiety and depression scores from all time points predicted poorer leadership (p-values&lt;.03). There was an interaction: higher anxiety and high depression predicted poorer leadership only in the context of poor sleep quality (not good or average sleep quality) [anxiety: R2=.04,F(1,159)=6.04,p=.02; interaction: R2=.03,F(1,155)=5.30,p=.02].

Conclusion
The current study identified a relationship between sleep quality and leadership ratings in ROTC cadets. This relationship was moderated by anxiety and depression. ROTC instructors should encourage ROTC Cadets to take advantage of sleep opportunities at Advanced Camp in order to maximize leadership potential.

Support
Support for this study came from the Military Operational Medicine Research Program (MOMRP) of the United States Army Medical Research and Development Command (USAMRDC).
Disclaimer: The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army or of the US
0189 Sleep Duration and Subjective Resilience to Sleep Loss Predict Functional Impairment in Elite Infantrymen During Military Training
Authors: Mickelson C A , Mantua J R , Burke T M , Choynowski J , Bessey A F , Naylor J A , Krizan Z , Sowden W J , Capaldi V F , McKeon A B 
Published: May 2020

Abstract

Introduction
Insufficient sleep during military operations is detrimental to cognition, physical performance, and general health outcomes. However, there is evidence of inter-individual differences in resilience to sleep loss. Therefore, some Soldiers may be more resilient to the effects of sleep loss than others. This study examined the relationship between sleep duration, resilience, and Soldier well-being during a deployment-readiness training event.

Methods
Seventy-six male Soldiers (aged 25.7±4.0y) from the 75th Ranger Regiment participated while undergoing a two-week training exercise. Surveys were administered at the completion of training and queried subjective measures of sleep duration during training, functional impairment (Walter Reed Functional Impairment Scale), and resilience to sleep loss (Iowa Resilience to Sleepiness Test; iREST). The independent relationships between sleep duration, resilience to sleep loss, and functional impairment were assessed using linear regressions. The interaction between sleep duration and resilience to sleep loss was assessed using SPSS Process (Model 1).

Results
Shorter sleep duration during training predicted higher functional impairment at the end of training (B=-.71, p=.001). Less resilience to sleep loss also predicted higher functional impairment (B=.07,p=.004). An interaction between sleep duration and resilience predicted Soldier impairment (R2 change: .06; F(1,68)=.17,p=.03). Individuals with both shorter sleep duration during training and less resilience had the highest functional impairment. Those with more sleep, and those with high resilience and less sleep, both had lower functional impairment.

Conclusion
This study suggests the iREST can be used as a quick, subjective screening tool to indicate who may be most vulnerable to the effects of sleep loss. Identifying individual resilience to sleep loss may be useful in the military context for prescribing sleep strategies before and during missions in order to enhance Soldier readiness and performance.

Support
Support for this study came from the Military Operational Medicine Research Program (MOMRP) of the United States Army Medical Research and Development Command (USAMRDC).
0200 Trait Mindfulness Moderates the Within-Person Relationship Between Sleep and Pain in Nurses
Authors: Mu C , Lee S 
Published: May 2020

Abstract

Introduction
Sleep and pain have a bidirectional relationship in clinical populations; however, we know less about the daily association in non-clinical but potentially vulnerable populations. Nurses are prone to poor sleep and pain symptoms due to work schedules and occupational stress. Implications from mindfulness-based interventions suggest that mindfulness may play a role in improving sleep and subsequently, reducing pain. The current study examined the within-person relationship between sleep and pain in nurses, and whether trait mindfulness moderates the relationship.

Methods
Participants were 60 nurses employed at a cancer hospital (Mage=35.35±11.83, 32% reported pain). For 14 consecutive days, ecological momentary assessment collected participants’ sleep characteristics, pain symptoms (i.e., chest pain, headaches, upset stomach, and other pain), and pain interference with daily activities. Trait mindfulness was measured using the 15-item Mindful Attention Awareness Scale. Multilevel modeling decomposed variances at the between- and within-person levels.

Results
At the between-person level, after controlling for sociodemographic covariates, more frequent insomnia symptoms (β=0.35) or lower sleep sufficiency (β=-0.19) were associated with more pain symptoms (ps&lt;.05). Inversely, individuals with more pain symptoms reported lower sleep sufficiency (β=-0.41, p&lt;.05). At the within-person level, after nights with poorer sleep quality (β=-0.08, p&lt;.01), lower sleep sufficiency (β=-0.08, p&lt;.01), or shorter sleep duration (β =-0.03, p&lt;.05), participants reported more pain symptoms the following day. There were significant interactions of mindfulness with (a) sleep sufficiency predicting pain interference and (b) sleep duration predicting number of pain symptoms, such that the adverse associations of less sufficient and shorter sleep with more pain were more apparent in those with lower mindfulness than those with higher mindfulness.

Conclusion
Although there was a bidirectional association between sleep and pain at the between-person level, sleep was more likely to be the predictor of pain at the within-person level in oncology nurses. The significant moderation by mindfulness suggest that promoting mindfulness among nurses, prone to having poor sleep and pain, may reduce the adverse impact of poor sleep on daily pain.

Support
This work was supported, in part, by the University of South Florida College of Behavioral & Community Sciences Internal Grant Program (PI: Lee, Grant No. 0134930).