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.

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.

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.

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.

"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.

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.

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.

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.

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.

Social jetlag and trajectories of mood symptoms and reward responsiveness in individuals at low-risk, high-risk, and with bipolar spectrum disorders: An ecological momentary assessment study.

A specific type of sleep disruption, social jetlag, involves an incongruence of sleep time between weekends and weekdays. This study investigated relationships between social jetlag and mood symptom lability and trajectories of daily reward responsiveness and mood symptoms. Participants (N = 130) from three groups (moderate reward sensitivity, high reward sensitivity, and high reward sensitivity with a diagnosed bipolar spectrum disorder [BSD]) were recruited from an ongoing longitudinal study based on their self-reported reward sensitivity and a diagnostic interview. For this study, they completed 20 days of ecological momentary assessment (EMA) of reward responsiveness and mood symptoms and a daily sleep diary. Social jetlag was significantly associated with differences in trajectories of depressive symptoms between groups. Specifically, greater social jetlag was associated with a greater increase in depressive symptoms over the 20 days for participants in the high reward sensitivity and BSD groups compared to the moderate reward sensitivity group. Social jetlag also was significantly associated with depressive symptom lability during the EMA period, but this finding was reduced to a trend toward significance when controlling for self-reported sleep duration. The study adds to the literature with methodological strengths including the EMA design and assessment of symptom and reward responsiveness trajectories.

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.

Prolonged Use of an Automated Insulin Delivery System Improves Sleep in Long-Standing Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia.

BACKGROUND: This study assessed changes in actigraphy-estimated sleep and glycemic outcomes after initiating automated insulin delivery (AID). METHODS: Ten adults with long-standing type 1 diabetes and impaired awareness of hypoglycemia (IAH) participated in an 18-month clinical trial assessing an AID intervention on hypoglycemia and counter-regulatory mechanisms. Data from eight participants (median age = 58 years) with concurrent wrist actigraph and continuous glucose monitoring (CGM) data were used in the present analyses. Actigraphs and CGM measured sleep and glycemic control at baseline (one week) and months 3, 6, 9, 12, 15, and 18 (three weeks) following AID initiation. HypoCount software integrated actigraphy with CGM data to separate wake and sleep-associated glycemic measures. Paired sample t-tests and Cohen's d effect sizes modeled changes and their magnitude in sleep, glycemic control, IAH (Clarke score), hypoglycemia severity (HYPO score), hypoglycemia exposure (CGM), and glycemic variability (lability index [LI]; CGM coefficient-of-variation [CV]) from baseline to 18 months. RESULTS: Sleep improved from baseline to 18 months (shorter sleep latency [P < .05, d = 1.74], later sleep offset [P < .05, d = 0.90], less wake after sleep onset [P < .01, d = 1.43]). Later sleep onset (d = 0.74) and sleep midpoint (d = 0.77) showed medium effect sizes. Sleep improvements were evident from 12 to 15 months after AID initiation and were preceded by improved hypoglycemia awareness (Clarke score [d = 1.18]), reduced hypoglycemia severity (HYPO score [d = 2.13]), reduced sleep-associated hypoglycemia (percent time glucose was < 54 mg/dL, < 60 mg/dL,< 70 mg/dL; d = 0.66-0.81), and reduced glucose variability (LI, d = 0.86; CV, d = 0.62). CONCLUSION: AID improved sleep initiation and maintenance. Improved awareness of hypoglycemia, reduced hypoglycemia severity, hypoglycemia exposure, and glucose variability preceded sleep improvements.This trial is registered with ClinicalTrials.gov NCT03215914 https://clinicaltrials.gov/ct2/show/NCT03215914.

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.

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.

Automated Insulin Delivery for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes with Hypoglycemia Unawareness.

Objective: Automated insulin delivery (AID) may benefit individuals with long-standing type 1 diabetes where frequent exposure to hypoglycemia impairs counterregulatory responses. This study assessed the effect of 18 months AID on hypoglycemia avoidance and glucose counterregulatory responses to insulin-induced hypoglycemia in long-standing type 1 diabetes complicated by impaired awareness of hypoglycemia. Methods: Ten participants mean ± standard deviation age 49 ± 16 and diabetes duration 34 ± 16 years were initiated on AID. Continuous glucose monitoring was paired with actigraphy to assess awake- and sleep-associated hypoglycemia exposure every 3 months. Hyperinsulinemic hypoglycemic clamp experiments were performed at baseline, 6, and 18 months postintervention. Hypoglycemia exposure was reduced by 3 months, especially during sleep, with effects sustained through 18 months (P ≤ 0.001) together with reduced glucose variability (P < 0.01). Results: Hypoglycemia awareness and severity scores improved (P < 0.01) with severe hypoglycemia events reduced from median (interquartile range) 3 (3-10) at baseline to 0 (0-1) events/person·year postintervention (P = 0.005). During the hypoglycemic clamp experiments, no change was seen in the endogenous glucose production (EGP) response, however, peripheral glucose utilization during hypoglycemia was reduced following intervention [pre: 4.6 ± 0.4, 6 months: 3.8 ± 0.5, 18 months: 3.4 ± 0.3 mg/(kg·min), P < 0.05]. There were increases over time in pancreatic polypeptide (Pre:62 ± 29, 6 months:127 ± 44, 18 months:176 ± 58 pmol/L, P < 0.01), epinephrine (Pre: 199 ± 53, 6 months: 332 ± 91, 18 months: 386 ± 95 pg/mL, P = 0.001), and autonomic symptom (Pre: 6 ± 2, 6 months: 6 ± 2, 18 months: 10 ± 2, P < 0.05) responses. Conclusions: AID led to a sustained reduction of hypoglycemia exposure. EGP in response to insulin-induced hypoglycemia remained defective, however, partial recovery of glucose counterregulation was evidenced by a reduction in peripheral glucose utilization likely mediated by increased epinephrine secretion and, together with improved autonomic symptoms, may contribute to the observed clinical reduction in hypoglycemia.

An examination of bidirectional associations between physical activity and mood symptoms among individuals diagnosed and at risk for bipolar spectrum disorders.

OBJECTIVES: Activation, a construct including energy and activity, is a central feature of Bipolar Spectrum Disorders (BSDs). Prior research found motor activity is associated with affect, and this relationship may be stronger for individuals with BSDs. The aims of this study were to investigate bidirectional relationships between physical activity and mood and evaluate whether bipolar risk status moderated potential associations. METHODS: Young adults at low-risk, high-risk, and diagnosed with BSD participated in a 20-day EMA study in which they wore an actiwatch to measure physical activity and sleep/wake cycles. They also reported depressive and hypo/manic symptoms three times daily. Multilevel linear models were estimated to examine how bipolar risk group moderated bidirectional relationships between physical activity and mood symptoms at within-day and between-day timescales. RESULTS: Physical activity was significantly associated with subsequent mood symptoms at the within-day level. The relationship between physical activity and depressive symptoms was moderated by BSD risk group. An increase in physical activity resulted in a greater reduction of depressive symptoms for the BSD group compared to the low-risk and high-risk groups. CONCLUSIONS: Interventions targeting activity like behavioral activation may improve residual inter-episode mood symptoms.

Keeping an eye on circadian time in clinical research and medicine.

BACKGROUND: Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to understand the contribution of the endogenous circadian component to these observed rhythms. CONTENT: The goal of this manuscript is to provide guidance on best practices in measuring metrics of endogenous circadian rhythms in humans and promote the inclusion of circadian rhythms assessments in studies of health and disease. Circadian rhythms affect all aspects of physiology. By specifying minimal experimental conditions for studies, we aim to improve the quality, reliability and interpretability of research into circadian and daily (i.e., time-of-day) rhythms and facilitate the interpretation of clinical and translational findings within the context of human circadian rhythms. We describe protocols, variables and analyses commonly used for studying human daily rhythms, including how to assess the relative contributions of the endogenous circadian system and other daily patterns in behaviours or the environment. We conclude with recommendations for protocols, variables, analyses, definitions and examples of circadian terminology. CONCLUSION: Although circadian rhythms and daily effects on health outcomes can be challenging to distinguish in practice, this distinction may be important in many clinical settings. Identifying and targeting the appropriate underlying (patho)physiology is a medical goal. This review provides methods for identifying circadian effects to aid in the interpretation of published work and the inclusion of circadian factors in clinical research and practice.

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.

The 3-Minute Psychomotor Vigilance Test Demonstrates Inadequate Convergent Validity Relative to the 10-Minute Psychomotor Vigilance Test Across Sleep Loss and Recovery.

The Psychomotor Vigilance Test (PVT) is a widely used behavioral attention measure, with the 10-min (PVT-10) and 3-min (PVT-3) as two commonly used versions. The PVT-3 may be comparable to the PVT-10, though its convergent validity relative to the PVT-10 has not been explicitly assessed. For the first time, we utilized repeated measures correlation (rmcorr) to evaluate intra-individual associations between PVT-10 and PVT-3 versions across total sleep deprivation (TSD), chronic sleep restriction (SR) and multiple consecutive days of recovery. Eighty-three healthy adults (mean ± SD, 34.7 ± 8.9 years; 36 females) received two baseline nights (B1-B2), five SR nights (SR1-SR5), 36 h TSD, and four recovery nights (R1-R4) between sleep loss conditions. The PVT-10 and PVT-3 were completed every 2 h during wakefulness. Rmcorr compared responses on two frequently used, sensitive PVT metrics: reaction time (RT) via response speed (1/RT) and lapses (RT > 500 ms on the PVT-10 and > 355 ms on the PVT-3) by day (e.g., B2), by study phase (e.g., SR1-SR5), and by time point (1000-2000 h). PVT 1/RT correlations were generally stronger than those for lapses. The majority of correlations (48/50 [96%] for PVT lapses and 38/50 [76%] for PVT 1/RT) were values below 0.70, indicating validity issues. Overall, the PVT-3 demonstrated inadequate convergent validity with the "gold standard" PVT-10 across two different types of sleep loss and across extended recovery. Thus, the PVT-3 is not interchangeable with the PVT-10 for assessing behavioral attention performance during sleep loss based on the design of our study and the metrics we evaluated. Our results have substantial implications for design and measure selection in laboratory and applied settings, including those involving sleep deprivation.

Impulsivity and sleep and circadian rhythm disturbance predict next-day mood symptoms in a sample at high risk for or with recent-onset bipolar spectrum disorder: An ecological momentary assessment study.

BACKGROUND: Impulsivity and sleep and circadian rhythm disturbance are core features of bipolar spectrum disorders (BSDs) that are antecedents to onset and persist even between mood episodes; their pervasive presence in BSD suggests that they may be particularly relevant to understanding BSD onset and course. Considerable research demonstrates bidirectional associations between impulsivity and sleep disturbance in healthy individuals; thus, it is important to examine how these features interact to impact BSD symptomatology. METHODS: Young adults (N = 107, 55% female, M age = 21.82 years) at high risk for developing BSD (based on high self-reported reward sensitivity) or with recent-onset BSD participated in ecological momentary assessment (EMA) to examine relationships between impulsivity, sleep and circadian rhythm alterations, and mood symptoms in everyday life. Impulsivity was measured via self-report/behavioral task, sleep was measured via actigraphy, circadian rhythms were measured via dim light melatonin onset (DLMO) time, and mood symptoms were measured three times daily via self-report. RESULTS: Multi-level modeling revealed that less total sleep time predicted increased next-day mood symptoms. Moreover, DLMO, total sleep time, and sleep onset latency moderated the relationship between impulsivity and EMA-assessed mood symptoms. Fewer minutes of sleep and later DLMO strengthened the positive relationship between impulsivity and mood symptoms. LIMITATIONS: Mood symptoms in our sample were mild; future studies should replicate findings in populations with more severe mood symptoms. CONCLUSIONS: This multi-method assessment of dynamic relationships revealed novel associations between impulsivity, sleep and circadian rhythm disturbance, and symptoms within individuals at high-risk for or with recent-onset BSD.