There are substantial individual differences (resilience and vulnerability) in performance resulting from sleep loss and psychosocial stress, but predictive potential biomarkers remain elusive. Similarly, marked changes in the cardiovascular system from sleep loss and stress include an increased risk for cardiovascular disease. It remains unknown whether key hemodynamic markers, including left ventricular ejection time (LVET), stroke volume (SV), heart rate (HR), cardiac index (CI), blood pressure (BP), and systemic vascular resistance index (SVRI), differ in resilient vs. vulnerable individuals and predict differential performance resilience with sleep loss and stress. We investigated for the first time whether the combination of total sleep deprivation (TSD) and psychological stress affected a comprehensive set of hemodynamic measures in healthy adults, and whether these measures differentiated neurobehavioral performance in resilient and vulnerable individuals. Thirty-two healthy adults (ages 27–53; 14 females) participated in a 5-day experiment in the Human Exploration Research Analog (HERA), a high-fidelity National Aeronautics and Space Administration (NASA) space analog isolation facility, consisting of two baseline nights, 39 h TSD, and two recovery nights. A modified Trier Social Stress Test induced psychological stress during TSD. Cardiovascular measure collection [SV, HR, CI, LVET, BP, and SVRI] and neurobehavioral performance testing (including a behavioral attention task and a rating of subjective sleepiness) occurred at six and 11 timepoints, respectively. Individuals with longer pre-study LVET (determined by a median split on pre-study LVET) tended to have poorer performance during TSD and stress. Resilient and vulnerable groups (determined by a median split on average TSD performance) showed significantly different profiles of SV, HR, CI, and LVET. Importantly, LVET at pre-study, but not other hemodynamic measures, reliably differentiated neurobehavioral performance during TSD and stress, and therefore may be a biomarker. Future studies should investigate whether the non-invasive marker, LVET, determines risk for adverse health outcomes.

Study Objectives Sleep restriction (SR) and total sleep deprivation (TSD) reveal well-established individual differences in Psychomotor Vigilance Test (PVT) performance. While prior studies have used different methods to categorize such resiliency/vulnerability, none have systematically investigated whether these methods categorize individuals similarly. Methods 41 adults participated in a 13-day laboratory study consisting of 2 baseline, 5 SR, 4 recovery, and one 36h TSD night. The PVT was administered every 2h during wakefulness. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and within each approach, six thresholds (±1 standard deviation and the best/worst performing 12.5%, 20%, 25%, 33%, and 50%) classified Resilient/Vulnerable groups. Kendall’s tau-b correlations examined the concordance of group categorizations of approaches within and between PVT lapses and 1/reaction time (RT). Bias-corrected and accelerated bootstrapped t-tests compared group performance. Results Correlations comparing the approaches ranged from moderate to perfect for lapses and zero to moderate for 1/RT. Defined by all approaches, the Resilient groups had significantly fewer lapses on nearly all study days. Defined by the Raw Score approach only, the Resilient groups had significantly faster 1/RT on all study days. Between-measures comparisons revealed significant correlations between the Raw Score approach for 1/RT and all approaches for lapses. Conclusion The three approaches defining vigilant attention resiliency/vulnerability to sleep loss resulted in groups comprised of similar individuals for PVT lapses but not for 1/RT. Thus, both method and metric selection for defining vigilant attention resiliency/vulnerability to sleep loss is critical.

Study Objectives Although trait-like individual differences in subjective responses to sleep restriction (SR) and total sleep deprivation (TSD) exist, reliable characterizations remain elusive. We comprehensively compared multiple methods for defining resilience and vulnerability by subjective metrics. Methods 41 adults participated in a 13-day experiment:2 baseline, 5 SR, 4 recovery, and one 36h TSD night. The Karolinska Sleepiness Scale (KSS) and the Profile of Mood States Fatigue (POMS-F) and Vigor (POMS-V) were administered every 2h. Three approaches (Raw Score [average SR score], Change from Baseline [average SR minus average baseline score], and Variance [intraindividual SR score variance]), and six thresholds (±1 standard deviation, and the highest/lowest scoring 12.5%, 20%, 25%, 33%, 50%) categorized Resilient/Vulnerable groups. Kendall’s tau-b correlations compared the group categorization’s concordance within and between KSS, POMS-F, and POMS-V scores. Bias-corrected and accelerated bootstrapped t-tests compared group scores. Results There were significant correlations between all approaches at all thresholds for POMS-F, between Raw Score and Change from Baseline approaches for KSS, and between Raw Score and Variance approaches for POMS-V. All Resilient groups defined by the Raw Score approach had significantly better scores throughout the study, notably including during baseline and recovery, whereas the two other approaches differed by measure, threshold, or day. Between-measure correlations varied in strength by measure, approach, or threshold. Conclusion Only the Raw Score approach consistently distinguished Resilient/Vulnerable groups at baseline, during sleep loss, and during recovery‒‒we recommend this approach as an effective method for subjective resilience/vulnerability categorization. All approaches created comparable categorizations for fatigue, some were comparable for sleepiness, and none were comparable for vigor. Fatigue and vigor captured resilience/vulnerability similarly to sleepiness but not each other.

Study Objectives Substantial individual differences exist in cognitive deficits due to sleep restriction (SR) and total sleep deprivation (TSD), with various methods used to define such neurobehavioral differences. We comprehensively compared numerous methods for defining cognitive throughput and working memory resiliency and vulnerability. Methods 41 adults participated in a 13-day experiment: 2 baseline, 5 SR, 4 recovery, and one 36h TSD night. The Digit Symbol Substitution Test (DSST) and Digit Span Test (DS) were administered every 2h. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and six thresholds (±1 standard deviation, and the best/worst performing 12.5%, 20%, 25%, 33%, 50%) classified Resilient/Vulnerable groups. Kendall’s tau-b correlations compared the group categorizations’ concordance within and between DSST number correct and DS total number correct. Bias-corrected and accelerated bootstrapped t-tests compared group performance.  Results The approaches generally did not categorize the same participants into Resilient/Vulnerable groups within or between measures. The Resilient groups categorized by the Raw Score approach had significantly better DSST and DS performance across all thresholds on all study days, while the Resilient groups categorized by the Change from Baseline approach had significantly better DSST and DS performance for several thresholds on most study days. By contrast, the Variance approach showed no significant DSST and DS performance group differences. Conclusion Various approaches to define cognitive throughput and working memory resilience/vulnerability to sleep loss are not synonymous. The Raw Score approach can be reliably used to differentiate resilient and vulnerable groups using DSST and DS performance during sleep loss.

In this review, we discuss reports of genotype-dependent interindividual differences in phenotypic neurobehavioral responses to total sleep deprivation or sleep restriction. We highlight the importance of using the candidate gene approach to further elucidate differential resilience and vulnerability to sleep deprivation in humans, although we acknowledge that other omics techniques and genome-wide association studies can also offer insights into biomarkers of such vulnerability. Specifically, we discuss polymorphisms in adenosinergic genes (ADA and ADORA2A), core circadian clock genes (BHLHE41/DEC2 and PER3), genes related to cognitive development and functioning (BDNF and COMT), dopaminergic genes (DRD2 and DAT), and immune and clearance genes (AQP4, DQB1*0602, and TNFα) as potential genetic indicators of differential vulnerability to deficits induced by sleep loss. Additionally, we review the efficacy of several countermeasures for the neurobehavioral impairments induced by sleep loss, including banking sleep, recovery sleep, caffeine, and naps. The discovery of reliable, novel genetic markers of differential vulnerability to sleep loss has critical implications for future research involving predictors, countermeasures, and treatments in the field of sleep and circadian science.