Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

Short-term and long-term phenotypic stability of actigraphic sleep metrics involving repeated sleep loss and recovery.

For the first time, we determined whether actigraphic-assessed sleep measures show inter-individual differences and intra-individual stability during baseline (BL) and recovery (REC) phases surrounding repeated total sleep deprivation (TSD). We conducted a 5-day experiment at Months 2 and 4 in two separate studies (N = 11). During each experiment, sleep measures were collected via wrist actigraphy during two BL 8 h time-in-bed (TIB) nights (B1, B2) and during two REC 8-10 h TIB nights (R1, R2). Intraclass correlation coefficients (ICCs) assessed actigraphic measure long-term stability between 2 and 4 months for (1) the pre-experimental phase before BL; and (2) the BL (B1 + B2), REC (R1 + R2), and BL and REC average (BL + REC) phases; and short-term stability at Month 2 and at Month 4; and (3) between B1 versus B2 and R1 versus R2 in each 5-day experiment. Nearly all ICCs during the pre-experimental, BL, REC, and BL + REC phases were moderate to almost perfect (0.446-0.970) between Months 2 and 4. B1 versus B2 ICCs were more stable (0.440-0.899) than almost all R1 versus R2 ICCs (-0.696 to 0.588) at Month 2 and 4. Actigraphic sleep measures show phenotypic long-term stability during BL and REC surrounding repeated TSD between 2 and 4 months. Furthermore, within each 5-day experiment at Month 2 and 4, the two BL nights before TSD were more stable than the two REC nights following TSD, likely due to increased R1 homeostatic pressure. Given the consistency of actigraphic measures across the short-term and long-term, they can serve as biomarkers to predict physiological and neurobehavioral responses to sleep loss.

Sleep deprivation attenuates neural responses to outcomes from risky decision-making.

Sleep loss impacts a broad range of brain and cognitive functions. However, how sleep deprivation affects risky decision-making remains inconclusive. This study used functional MRI to examine the impact of one night of total sleep deprivation (TSD) on risky decision-making behavior and the underlying brain responses in healthy adults. In this study, we analyzed data from N = 56 participants in a strictly controlled 5-day and 4-night in-laboratory study using a modified Balloon Analogue Risk Task. Participants completed two scan sessions in counter-balanced order, including one scan during rested wakefulness (RW) and another scan after one night of TSD. Results showed no differences in participants' risk-taking propensity and risk-induced activation between RW and TSD. However, participants showed significantly reduced neural activity in the anterior cingulate cortex and bilateral insula for loss outcomes, and in bilateral putamen for win outcomes during TSD compared with RW. Moreover, risk-induced activation in the insula negatively correlated with participants' risk-taking propensity during RW, while no such correlations were observed after TSD. These findings suggest that sleep loss may impact risky decision-making by attenuating neural responses to decision outcomes and impairing brain-behavior associations.

Reflections on Several Landmark Advances in Circadian Biology.

Circadian Biology intersects with diverse scientific domains, intricately woven into the fabric of organismal physiology and behavior. The rhythmic orchestration of life by the circadian clock serves as a focal point for researchers across disciplines. This retrospective examination delves into several of the scientific milestones that have fundamentally shaped our contemporary understanding of circadian rhythms. From deciphering the complexities of clock genes at a cellular level to exploring the nuances of coupled oscillators in whole organism responses to stimuli. The field has undergone significant evolution lately guided by genetics approaches. Our exploration here considers key moments in the circadian-research landscape, elucidating the trajectory of this discipline with a keen eye on scientific advancements and paradigm shifts.

Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

Light Therapy for Adolescent Depression: A Scoping Review.

PURPOSE: Depressive disorders in adolescents are a major health concern associated with developmental, social, and educational impairment. Bright Light Therapy (BLT) is a feasible and effective treatment for depressive disorders in adults, but few controlled trials have been conducted with children or adolescents. This scoping review focuses on the current state of knowledge for BLT in the treatment of adolescent depression. We reviewed the literature for novel data and methodologic approaches using BLT and pediatric and young adult populations. RECENT FINDINGS: BLT is a tolerable treatment with few side effects. However, there is a marked lack of well-powered studies to support BLT as a treatment for depressive disorders in adolescent populations. Given evidence of tolerability and positive treatment effect on depression in the adult literature, research is needed to establish the efficacy, feasibility, and acceptability of BLT in adolescents.

The relationship between physical activity states and depressive symptoms: Using ambulatory assessment to characterize day-to-day associations among individuals with and without bipolar spectrum disorder.

INTRODUCTION: The role of activation in the pathogenesis of bipolar spectrum disorders (BSD) is of growing interest. Physical activity is known to improve mood, but it is unclear whether low activity levels contribute to inter-episode depressive symptoms observed in BSD. This study examined whether sedentary and vigorous activity, as well as the timing of the activity, were differentially associated with next-day depressive symptoms for individuals at low risk for BSD, high-risk for BSD, and diagnosed with BSD. METHODS: Young adults (n = 111, ages 18-27) from three groups (low BSD risk, high BSD risk, and BSD diagnosis), participated in a 20-day ecological momentary assessment study. Physical activity was measured via wrist actigraphy counts. The percentage of time awake spent in sedentary, light, moderate, and vigorous activity states was calculated, as was the percentage of morning hours and evening hours in each activity state. Multilevel models examined whether the BSD risk group moderated associations between sedentary and vigorous activity and depressive symptoms, which were assessed three times daily. RESULTS: There were no between-group differences in time spent in each activity state, nor were there main effects of sedentary or vigorous activity on depression. Increased time spent engaging in vigorous activity was associated with a greater reduction in subsequent depressive symptoms for the BSD group. An increase in the evening, but not morning, vigorous activity was significantly associated with a reduction in subsequent depressive symptoms for the BSD group after controlling for chronotype. CONCLUSIONS: Interventions targeting physical activity may effectively help regulate inter-episode mood disturbances in BSD.

Meta-analysis of sleep deprivation in the acute treatment of bipolar depression.

BACKGROUND: Sleep deprivation (SD) is an antidepressant intervention with multiple administration formats that has been investigated primarily with uncontrolled clinical trials and qualitative reviews of the literature. The validity and applicability of these findings to the treatment of bipolar depression (BPD) is uncertain. METHODS: A PRISMA-based systematic review of the literature and meta-analysis were conducted to determine the efficacy of SD in the treatment of BPD and to identify moderator variables that influence response rate. RESULTS: From a sample of 15 studies covering 384 patients, the overall, mean response rate to SD was 47.6% (CI 36.0%, 59.5%). This response rate compared post-SD to pre-SD depression scores, and not to a placebo control condition. Of several potential moderating variables examined, the use of adjunctive pharmacotherapy achieved statistical significance with response rates of 59.4% [CI 48.5, 69.5] for patients using adjunctive medication vs 27.4% [CI 17.8, 39.8] for patients not using adjunctive medication. CONCLUSIONS: This meta-analysis of SD in the treatment of BPD found an overall, response rate of almost 50%, reinforcing earlier estimates of efficacy. The use of adjunctive pharmacotherapy had a statistically significant moderating effect on SD response suggesting that clinical practice should routinely pair these interventions. These findings provide a higher level of evidence supporting the use of SD, especially when used with medication, and should inform future management guidelines for the treatment of BPD.

Human and rat gut microbiome composition is maintained following sleep restriction.

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology.

AIMS: To systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)-bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI-BP)-and propose treatment recommendations based on a synthesis of the evidence. METHODS: PRISMA-based systematic review of the literature. RESULTS: The acute antidepressant (AD) efficacy of LT was supported by several open-label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti-manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant activity, conflicting evidence of both antimanic and maintenance efficacy, and support from two case series of improved sleep in both acute and euthymic states. IPSRT monotherapy for bipolar II depression had acute response rates of 41%, 67%, and 67.4% in two open studies and one RCT, respectively; as adjunctive therapy for bipolar depression in one RCT, and efficacy in reducing relapse in two RCTs. Among euthymic BD subjects with insomnia, a single RCT found CBTI-BP effective in delaying manic relapse and improving sleep. Chronotherapies were generally safe and well-tolerated. CONCLUSIONS: The outcome literature on the adjunctive use of chronotherapeutic treatments for BP is variable, with evidence bases that differ in size, study quality, level of evidence, and non-standardized treatment protocols. Evidence-informed practice recommendations are offered.

Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt.

Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets (n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction (P < 0.05, false-discovery rate < 0.2). Elevated phospholipids were also noted after sleep restriction in both species, as well as metabolites associated with an oxidizing environment. In addition, polar metabolites reflective of neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.

Neurobehavioral Effects and Biomarkers of Sleep Loss in Healthy Adults.

PURPOSE OF REVIEW: This article reviews the neurobehavioral deficits resulting from sleep loss in adults, various countermeasures to mitigate these effects, and biomarkers to identify individual differences in neurobehavioral responses. RECENT FINDINGS: Total sleep deprivation and chronic sleep restriction increase the homeostatic sleep drive and diminish waking neurobehavioral functioning, producing deficits in attention, memory and cognitive speed, increases in sleepiness and fatigue, and unstable wakefulness. Recovery sleep, extension of sleep, and use of caffeine and/or naps are all effective countermeasures to mitigate these responses. Candidate gene and various "omics" approaches have identified biomarkers that may predict such responses. Sleep loss is increasingly prevalent and produces reliable, differential neurobehavioral deficits across individuals. Recent research has identified biomarkers to predict these responses, though future work is warranted, such that precise determination of who will develop neurobehavioral decrements from sleep loss will be possible.

Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing.

The success of interplanetary human spaceflight will depend on many factors, including the behavioral activity levels, sleep, and circadian timing of crews exposed to prolonged microgravity and confinement. To address the effects of the latter, we used a high-fidelity ground simulation of a Mars mission to objectively track sleep-wake dynamics in a multinational crew of six during 520 d of confined isolation. Measurements included continuous recordings of wrist actigraphy and light exposure (4.396 million min) and weekly computer-based neurobehavioral assessments (n = 888) to identify changes in the crew's activity levels, sleep quantity and quality, sleep-wake periodicity, vigilance performance, and workload throughout the record-long 17 mo of mission confinement. Actigraphy revealed that crew sedentariness increased across the mission as evident in decreased waking movement (i.e., hypokinesis) and increased sleep and rest times. Light exposure decreased during the mission. The majority of crewmembers also experienced one or more disturbances of sleep quality, vigilance deficits, or altered sleep-wake periodicity and timing, suggesting inadequate circadian entrainment. The results point to the need to identify markers of differential vulnerability to hypokinesis and sleep-wake changes during the prolonged isolation of exploration spaceflight and the need to ensure maintenance of circadian entrainment, sleep quantity and quality, and optimal activity levels during exploration missions. Therefore, successful adaptation to such missions will require crew to transit in spacecraft and live in surface habitats that instantiate aspects of Earth's geophysical signals (appropriately timed light exposure, food intake, exercise) required for temporal organization and maintenance of human behavior.

A new likelihood ratio metric for the psychomotor vigilance test and its sensitivity to sleep loss.

The Psychomotor Vigilance Test (PVT) is a widely used assay of behavioural alertness sensitive to the effects of sleep loss and circadian misalignment. However, there is currently no accepted PVT composite outcome metric that captures response slowing, attentional lapses and compensatory premature reactions observed typically in sleep-deprived subjects. We developed a novel likelihood ratio metric (LRM) based on relative frequency distributions in 50 categories of reaction times (RT) and false starts in alert and sleep-deprived subjects (acute total sleep deprivation: n = 31 subjects). The LRM had the largest effect size both in a 33-h total sleep deprivation protocol [1.96; 95% confidence interval (CI): 1.61-2.44; followed by response speed 1/RT, effect size 1.93, 95% CI: 1.55-2.65] and in a chronic partial sleep restriction protocol (1.22; 95% CI: 0.96-1.59; followed by response speed 1/RT, effect size 1.21, 95% CI: 0.94-1.59; 5 nights at 4 h sleep per night; n = 43 subjects). LRM scores correlated highly with response speed (R(2 ) = 0.986), and less well with five other common PVT outcome metrics (R(2 ) = 0.111-0.886). In conclusion, the new LRM is a sensitive PVT outcome metric with high statistical power that takes subtle sleep loss-related changes in the distribution of reaction times (including false starts) into account, is not prone to outliers, does not require baseline data and can be calculated and interpreted easily. Congruence between LRM and PVT response speed and their similar effect size rankings support the use of response speed as the primary, most sensitive and most parsimonious standard PVT outcome metric for determining neurobehavioural deficits from sleep loss.

"Count on Sleep": an OSA awareness project update.

Obstructive sleep apnea (OSA) is a common, chronic sleep-related breathing disorder that affects approximately 12% of the US adult population. Greater public awareness of OSA is necessary to decrease the number of people with undiagnosed or untreated OSA and reduce the negative health consequences of unrecognized OSA. In 2021, the American Academy of Sleep Medicine initiated the "Count on Sleep" project in partnership with key stakeholders with the objective of raising the awareness of OSA among the public, health care providers, and public health officials. Four workgroups implemented strategies and completed tasks focused on increasing OSA awareness in their targeted areas to address the objectives of the project including (1) Public Awareness and Communications, (2) Provider Education, (3) Tool Development and Surveillance, and (4) a Strategic Planning workgroup that coordinated efforts across the project. Over the first 2 years, workgroups made substantial progress toward project goals including holding "listening sessions" with representatives of communities disproportionately affected by OSA and its consequences, developing resources for primary care providers that can be easily accessed and used in practice, and developing a brief survey for use in estimating and tracking OSA risk across the population. Over the first 2 project years, workgroups made significant progress in advancing efforts to increase awareness of OSA in US communities. The third year of the project will focus on dissemination of campaign materials and resources for all targeted groups, including the public, health care professionals, and public health professionals. CITATION: Martin JL, Rowley J, Goel N, et al. "Count on Sleep": an OSA awareness project update. J Clin Sleep Med. 2024;20(2):303-307.

Reward sensitivity and social rhythms during goal-striving: An ecological momentary assessment investigation of bipolar spectrum disorders.

BACKGROUND: The reward/circadian rhythm model of bipolar spectrum disorders (BSDs) posits that when individuals with hypersensitive reward systems encounter reward-relevant events, they experience social and circadian rhythm disruption, leading to mood symptoms. The aim of the current study is to test an element of this theoretical model by investigating changes in social rhythms during and after an ecologically-valid reward-relevant event and evaluating whether the strength of these associations differ by trait reward sensitivity and BSD diagnostic group. METHODS: Young adults from three groups (low BSD risk with moderate reward sensitivity [MRew], high BSD risk with high reward sensitivity [HRew], and high reward sensitivity with BSD [HRew+BSD]) completed a reward responsiveness task and 20-day ecological momentary assessment study structured around a participant-specific goal occurring on day 15. Social rhythm disruption (SRD) and social rhythm regularity (SRR) were assessed daily. Multilevel models examined whether reward sensitivity and group moderated associations between study phase (baseline [days 1-5], goal-striving [days 16-20], or outcome [days 16-20]) and social rhythms. RESULTS: Participants experienced greater SRD after the goal-striving event during the outcome phase, compared to the baseline phase. The HRew+BSD group had significant decreases in SRR during the outcome phase, and this pattern differed significantly from the low-risk and high-risk groups. Greater task reward responsiveness also was associated with significant decreases in SRR during the outcome phase. LIMITATIONS: This study did not test whether social rhythm irregularity was associated with subsequent mood change. CONCLUSIONS: Participants exhibited social rhythm changes over the course of this ecologically valid goal-striving period, providing evidence for the interplay between reward-activating events and social rhythms. The HRew+BSD group showed a distinct pattern in which their social rhythms were more irregular after completing reward-relevant goal-striving that was not observed for the low-BSD risk or high-BSD risk groups. These findings provide additional support for Interpersonal and Social Rhythms Therapy.

Bright Light Therapy for Major Depressive Disorder in Adolescent Outpatients: A Preliminary Study.

BACKGROUND: Bright light therapy (BLT) has not been well-studied in adolescents with major depressive disorder, particularly in outpatient settings. METHODS: We conducted an 8-week clinical trial of BLT in adolescents recruited from a primary care practice with moderate to severe major depression. Acceptability and feasibility were defined by daily use of the light box and integration into daily routines. To assess treatment effects, we utilized the Short Mood and Feelings Questionnaire (SMFQ) and actigraphic sleep variables. RESULTS: Of the nine enrolled adolescents, the rate of daily use of the light therapy box was 100% at week 2, 78% at week 4 (n = 7), and 67% at weeks 6 and 8 (n = 6). Participants were better able to integrate midday BLT compared to morning BLT into their day-to-day routines. Mean depression scores improved during the 2-week placebo lead-in (dim red light-DRL) and continued to show significant improvement through 6 weeks of BLT. Sleep efficiency increased significantly (p = 0.046), and sleep onset latency showed a trend toward a significant decrease (p = 0.075) in the BLT phase compared to the DRL phase. CONCLUSION: Bright light treatment that was self-administered at home was feasible, acceptable, and effective for adolescent outpatients with depression. Findings support the development of larger, well-powered, controlled clinical trials of BLT in coordination with primary care.

The Negative Effects of Travel on Student Athletes Through Sleep and Circadian Disruption.

Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel away from their home campus. Clearly such stressors can have negative impacts on both their academic and athletic performances as well as on their health. These concerns are made more acute by recent proposals and decisions to reorganize major collegiate athletic conferences. These rearrangements will require more multi-day travel that interferes with the academic work and personal schedules of athletes. Of particular concern is additional east-west travel that results in circadian rhythm disruptions commonly called jet lag that contribute to the loss of amount as well as quality of sleep. Circadian misalignment and sleep deprivation and/or sleep disturbances have profound effects on physical and mental health and performance. We, as concerned scientists and physicians with relevant expertise, developed this white paper to raise awareness of these challenges to the wellbeing of our student-athletes and their co-travelers. We also offer practical steps to mitigate the negative consequences of collegiate travel schedules. We discuss the importance of bedtime protocols, the availability of early afternoon naps, and adherence to scheduled lighting exposure protocols before, during, and after travel, with support from wearables and apps. We call upon departments of athletics to engage with sleep and circadian experts to advise and help design tailored implementation of these mitigating practices that could contribute to the current and long-term health and wellbeing of their students and their staff members.

Impact of bimonthly repeated total sleep deprivation and recovery sleep on cardiovascular indices.

Since short sleep duration adversely affects cardiovascular (CV) health, we investigated the effects of exposures to total sleep deprivation (TSD), and baseline (BL) and recovery (REC) sleep on CV measures. We conducted a 5-day experiment at months 2 and 4 in two separate studies (N = 11 healthy adults; 5 females). During these repeated experiments, CV measures [stroke volume (SV), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular ejection time, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) and mean arterial pressure (MAP)] were collected at three assessment time points after: (1) two BL 8 h time-in-bed (TIB) sleep opportunity nights; (2) a TSD night; and (3) two REC 8-10 h TIB nights. CV measures were also collected pre-study. TSD significantly increased SV and CI, and decreased SVRI, with large effect sizes, which importantly were reversed with recovery, indicating these measures are possible novel biomarkers for assessing the adverse consequences of TSD. Pre-study SV, CI, SVRI, HR, SBP, and MAP measures also significantly associated with TSD CV responses at months 2 and 4 [Pearson's r: 0.615-0.862; r2 : 0.378-0.743], indicating they are robust correlates of future TSD CV responses. Our novel findings highlight the critical impact of sleep on CV health across time.

Cardiovascular measures display robust phenotypic stability across long-duration intervals involving repeated sleep deprivation and recovery.

Introduction: We determined whether cardiovascular (CV) measures show trait-like responses after repeated total sleep deprivation (TSD), baseline (BL) and recovery (REC) exposures in two long-duration studies (total N = 11 adults). Methods: A 5-day experiment was conducted twice at months 2 and 4 in a 4-month study (N = 6 healthy adults; 3 females; mean age ± SD, 34.3 ± 5.7 years; mean BMI ± SD, 22.5 ± 3.2 kg/m2), and three times at months 2, 4, and 8 in an 8-month study (N = 5 healthy adults; 2 females; mean age ± SD, 33.6 ± 5.17 years; mean BMI ± SD, 27.1 ± 4.9 kg/m2). Participants were not shift workers or exposed to TSD in their professions. During each experiment, various seated and standing CV measures were collected via echocardiography [stroke volume (SV), heart rate (HR), cardiac index (CI), left ventricular ejection time (LVET), and systemic vascular resistance index (SVRI)] or blood pressure monitor [systolic blood pressure (SBP)] after (1) two BL 8h time in bed (TIB) nights; (2) an acute TSD night; and (3) two REC 8-10 h TIB nights. Intraclass correlation coefficients (ICCs) assessed CV measure stability during BL, TSD, and REC and for the BL and REC average (BL + REC) across months 2, 4, and 8; Spearman's rho assessed the relative rank of individuals' CV responses across measures. Results: Seated BL (0.693-0.944), TSD (0.643-0.962) and REC (0.735-0.960) CV ICCs showed substantial to almost perfect stability and seated BL + REC CV ICCs (0.552-0.965) showed moderate to almost perfect stability across months 2, 4, and 8. Individuals also exhibited significant, consistent responses within seated CV measures during BL, TSD, and REC. Standing CV measures showed similar ICCs for BL, TSD, and REC and similar response consistency. Discussion: This is the first demonstration of remarkably robust phenotypic stability of a number of CV measures in healthy adults during repeated TSD, BL and REC exposures across 2, 4, and 8 months, with significant consistency of responses within CV measures. The cardiovascular measures examined in our studies, including SV, HR, CI, LVET, SVRI, and SBP, are useful biomarkers that effectively track physiology consistently across long durations and repeated sleep deprivation and recovery.