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.

Exercising the Sleepy-ing Brain: Exercise, Sleep, and Sleep Loss on Memory.

We examine the novel hypothesis that physical exercise and sleep have synergistic effects on memory. Exercise can trigger mechanisms that can create an optimal brain state during sleep to facilitate memory processing. The possibility that exercise could counteract the deleterious effects of sleep deprivation on memory by protecting neuroplasticity also is discussed.

Reductions in sleep quality and circadian activity rhythmicity predict longitudinal changes in objective and subjective cognitive functioning in women treated for breast cancer.

PURPOSE: To examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC). PATIENTS AND METHODS: Sixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year). RESULTS: WBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood. CONCLUSION: Objective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

The Role of Vaccination Interventions to Promote HPV Vaccine Uptake Rates in a College-Aged Population: a Systematic Review.

This systematic review provided synthesized evidence regarding the effectiveness of the interventions promoting the human papillomavirus (HPV) vaccination in college-aged population. The HPV infection is the most prevailing sexually transmitted disease. Despite the availability and effectiveness of the 9-Valent HPV vaccine, the vaccine coverage among young adults remained low. In witness to the increasing burden of HPV-related infections and cancers, research focused on the vaccination interventions should be conducted to determine the effectiveness of the vaccination strategy and address the gap. The search was conducted through PubMed, Cochrane, and CINAL. Studies were included if they (1) included vaccination programs, (2) target population was young adults aged 17-26, (3) examined factors associated with the intervention effectiveness, (4) were published in English, and (5) were published between February 2010 and February 2020. HPV-related knowledge and intentions toward HPV vaccination were all reported increased after the intervention. Increased HPV vaccination intentions were found associated with the increased vaccine initiation and completion. Among bisexual or homosexual individuals, females were found more likely to complete the HPV dose 2 and 3. The review findings suggested using vaccination interventions incorporated with educational components to promote vaccine uptake among young adults. Supportive interventions tailored to different populations and settings are crucial to address the suboptimal HPV-related knowledge and vaccination status among the young beneficiaries.

Testing the sleep hygiene recommendation against nighttime exercise.

PURPOSE: Experts have recommended exercise for improved sleep, but often with the caveat that one should avoid nighttime exercise. The aim of this study was to challenge this recommendation in a sample who might be most prone to sleep impairment after nighttime exercise. The secondary aims were to assess whether or not post-treatment sleep was correlated with anxiolytic effects or downregulation of body temperature. METHODS: Twelve sedentary adults with insomnia completed two treatments (separated by 2-5 days) in counterbalanced order: (1) 30 min of moderate treadmill exercise (60-70% maximum heart rate) + 15 min of moderate resistance exercise and (2) a control treatment (reading). Each treatment was completed 2 h before bedtime and followed by a 10-min shower, a light snack, 8 h of polysomnographic recording, and a sleep questionnaire. State anxiety was assessed before and 30 min after each treatment and 10 min before bedtime. Body temperature was assessed from pre-exercise to wake time. RESULTS: No significant treatment differences in sleep were found, and Hedges g paired comparisons indicated small effect sizes; however, two participants had severely disturbed objective sleep following exercise. Significant correlations were found between change in state anxiety from pre-exercise to bedtime and TST (r = 0.69, p = 0.03). Stage 1 (r = 0.67, p = 0.03), WASO (r = 0.69, p = 0.03), and sleep efficiency (r = 0.66, p = 0.02). No significant correlations were found of sleep with temperature decline. CONCLUSIONS: Profound sleep disturbance after exercise in some participants, and no marked sleep improvement in the others, provides some support for caution regarding late-night exercise for sedentary individuals with insomnia.

Recruitment and retention of underrepresented and vulnerable populations to research.

Per principles outlined in the Belmont Report, research involving human subjects should minimize risks to participants and maximize benefits to participants and society. Recruitment of participants should be equitable. Once enrolled, participants have the right to withdraw at any point. Researchers must balance these principles with pressures to meet enrollment goals and, in the context of repeated-measures designs, retain participants across time. The purpose of this perspective is to describe the approach and corresponding activities for recruiting and retaining underrepresented and vulnerable populations that are the focus of a transdisciplinary academic research center. To this effort, we offer diverse disciplinary backgrounds, experience working with a wide range of populations (from infants to older adults and across multiple health conditions), and spanning a variety of research designs. Effective strategies offered include partnering with community entities, approaching potential participants where they are and at a time of readiness, using population-appropriate modes of communication and data collection, conducting study activities in familiar settings and at convenient times, maintaining frequent contact, and offering meaningful incentives. These strategies are consistent with population-specific reports found in the extant literature and underscore their cross-cutting nature, with adaptations based on participant and community partner needs and preferences.

The impact of summer vacation on children's obesogenic behaviors and body mass index: a natural experiment.

BACKGROUND: Children's BMI gain accelerates during summer. The Structured Days Hypothesis posits that the lack of the school day during summer vacation negatively impacts children's obesogenic behaviors (i.e., physical activity, screen time, diet, sleep). This natural experiment examined the impact of summer vacation on children's obesogenic behaviors and body mass index (BMI). METHODS: Elementary-aged children (n = 285, 5-12 years, 48.7% male, 57.4% African American) attending a year-round (n = 97) and two match-paired traditional schools (n = 188) in the United States participated in this study. Rather than taking a long break from school during the summer like traditional schools, year-round schools take shorter and more frequent breaks from school. This difference in school calendars allowed for obesogenic behaviors to be collected during three conditions: Condition 1) all children attend school, Condition 2) year-round children attend school while traditional children were on summer vacation, and Condition 3) summer vacation for all children. Changes in BMI z-score were collected for the corresponding school years and summers. Multi-level mixed effects regressions estimated obesogenic behaviors and monthly zBMI changes. It was hypothesized that children would experience unhealthy changes in obesogenic behaviors when entering summer vacation because the absence of the school day (i.e., Condition 1 vs. 2 for traditional school children and 2 vs. 3 for year-round school children). RESULTS: From Condition 1 to 2 traditional school children experienced greater unhealthy changes in daily minutes sedentary (∆ = 24.2, 95CI = 10.2, 38.2), screen time minutes (∆ = 33.7, 95CI = 17.2, 50.3), sleep midpoint time (∆ = 73:43, 95CI = 65:33, 81:53), and sleep efficiency percentage (-∆ = 0.7, 95CI = -1.1, - 0.3) when compared to year-round school children. Alternatively, from Condition 2 to 3 year-round school children experienced greater unhealthy changes in daily minutes sedentary (∆ = 54.5, 95CI = 38.0, 70.9), light physical activity minutes (∆ = - 42.2, 95CI = -56.2, - 28.3) MVPA minutes (∆ = - 11.4, 95CI = -3.7, - 19.1), screen time minutes (∆ = 46.5, 95CI = 30.0, 63.0), and sleep midpoint time (∆ = 95:54, 95CI = 85:26, 106:22) when compared to traditional school children. Monthly zBMI gain accelerated during summer for traditional (∆ = 0.033 95CI = 0.019, 0.047) but not year-round school children (∆ = 0.004, 95CI = -0.014, 0.023). CONCLUSIONS: This study suggests that the lack of the school day during summer vacation negatively impacts sedentary behaviors, sleep timing, and screen time. Changes in sedentary behaviors, screen time, and sleep midpoint may contribute to accelerated summer BMI gain. Providing structured programming during summer vacation may positively impact these behaviors, and in turn, mitigate accelerated summer BMI gain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03397940 . Registered January 12th 2018.

Human circadian phase-response curves for exercise.

KEY POINTS: Exercise elicits circadian phase-shifting effects, but additional information is needed. The phase-response curve describing the magnitude and direction of circadian rhythm phase shifts, depending on the time of the zeigeber (time cue) stimulus, is the most fundamental chronobiological tool for alleviating circadian misalignment and related morbidity. Fifty-one older and 48 young adults followed a circadian rhythms measurement protocol for up to 5.5 days, and performed 1 h of moderate treadmill exercise for 3 consecutive days at one of eight times of the day/night. Temporal changes in the phase of 6-sulphatoxymelatonin (aMT6s) were measured from evening onset, cosine acrophase, morning offset and duration of excretion. Significant phase-response curves were established for aMT6 onset and acrophase with large phase delays from 7:00 pm to 10:00 pm and large phase advances at both 7:00 am and from 1:00 pm to 4:00 pm. Delays or advances would be desired, for example, for adjustment to westward or eastward air travel, respectively. Along with known synergism with bright light, the above PRCs with a second phase advance region (afternoon) could support both practical and clinical applications. ABSTRACT: Although bright light is regarded as the primary circadian zeitgeber, its limitations support exploring alternative zeitgebers. Exercise elicits significant circadian phase-shifting effects, but fundamental information regarding these effects is needed. The primary aim of the present study was to establish phase-response curves (PRCs) documenting the size and direction of phase shifts in relation to the circadian time of exercise. Aerobically fit older (n = 51; 59-75 years) and young adults (n = 48; 18-30 years) followed a 90 min laboratory ultrashort sleep-wake cycle (60 min wake/30 min sleep) for up to 5½ days. At the same clock time on three consecutive days, each participant performed 60 min of moderate treadmill exercise (65-75% of heart rate reserve) at one of eight times of day/night. To describe PRCs, phase shifts were measured for the cosine-fitted acrophase of urinary 6-sulphatoxymelatonin (aMT6s), as well as for the evening rise, morning decline and change in duration of aMT6s excretion. Significant PRCs were found for aMT6s acrophase, onset and duration, with peak phase advances corresponding to clock times of 7:00 am and from 1:00 pm to 4:00 pm, delays from 7:00 pm to 10:00 pm, and minimal shifts around 4:00 pm and 2:00 am. There were no significant age or sex differences. The amplitudes of the aMT6s onset and acrophase PRCs are comparable to expectations for bright light of equal duration. The phase advance to afternoon exercise and the exercise-induced PRC for change in aMT6s duration are novel findings. The results support further research exploring additive phase-shifting effects of bright light and exercise and health benefits.

Behavioral Strategies, Including Exercise, for Addressing Insomnia.

Cognitive-behavioral therapy for insomnia is superior to sleeping pills for treating insomnia, and its accessibility is rapidly improving. Exercise can also promote sleep in insomnia. A list of recommendations on good sleep practices can be applied prior to consulting with a clinician and can often resolve insomnia symptoms. SUMMARY STATEMENT: Insomnia is associated with negative psychological and physiological health outcomes. Established behavioral strategies for addressing insomnia such as adoption of good sleep habits and engagement in Cognitive Behavioral Therapy for Insomnia have documented efficacy. Exercise is also efficacious with unique health benefits.

Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise.

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210-2340 h, (2) treadmill exercise alone from 2210-2340 h, or (3) bright light (2210-2340 h) followed by exercise from 0410-0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect.

Association of Markers of Inflammation with Sleep and Physical Activity Among People Living with HIV or AIDS.

This study examined associations of sleep and minutes spent in moderate-vigorous physical activity (MVPA) with C-reactive protein (CRP) and interleukin (IL)-6 among persons living with HIV. Cross-sectional analyses (n = 45) focused on associations of inflammatory outcomes (i.e., CRP and IL-6) with actigraph-derived sleep duration, latency, and efficiency; sleep onset; wake time; and wake-after-sleep-onset; as well as MVPA. Least square means for CRP and IL-6 by levels of sleep and MVPA were computed from general linear models. Individuals below the median of sleep duration, above the median for sleep onset, and below the median of MVPA minutes had higher CRP or IL-6 levels. Generally, individuals with both low MVPA and poor sleep characteristics had higher inflammation levels than those with more MVPA and worse sleep. Understanding the combined impact of multiple lifestyle/behavioral factors on inflammation could inform intervention strategies to reduce inflammation and therefore, chronic disease risk.

Differential increase in prevalence estimates of inadequate sleep among black and white Americans.

BACKGROUND: The National Health Interview Survey (NHIS) was used to ascertain whether increases in inadequate sleep differentially affected black and white Americans. We tested the hypothesis that prevalence estimates of inadequate sleep were consistently greater among blacks, and that temporal changes have affected these two strata differentially. METHODS: NHIS is an ongoing cross-sectional study of non-institutionalized US adults (≥18 years) providing socio-demographic, health risk, and medical factors. Sleep duration was coded as very short sleep [VSS] (<5 h), short sleep [SS] (5-6 h), or long sleep [LS] (>8 h), referenced to 7-8 h sleepers. Analyses adjusted for NHIS' complex sampling design using SAS-callable SUDAAN. RESULTS: Among whites, the prevalence of VSS increased by 53% (1.5% to 2.3%) from 1977 to 2009 and the prevalence of SS increased by 32% (19.3% to 25.4 %); prevalence of LS decreased by 30% (11.2% to 7.8%). Among blacks, the prevalence of VSS increased by 21% (3.3% to 4.0%) and the prevalence of SS increased by 37% (24.6 % to 33.7%); prevalence of LS decreased by 42% (16.1% to 9.4%). Adjusted multinomial regression analysis showed that odds of reporting inadequate sleep for whites were: VSS (OR = 1.40, 95% CI = 1.13-1.74, p < 0.001), SS (OR = 1.34, 95 % CI = 1.25-1.44, p < 0.001), and LS (OR = 0.94, 95% CI = 0.85-1.05, NS). For blacks, estimates were: VSS (OR = 0.83, 95% CI = 0.60-1.40, NS), SS (OR = 1.21, 95% CI = 1.05-1.50, p < 0.001), and LS (OR = 0.84, 95% CI = 0.64-1.08, NS). CONCLUSIONS: Blacks and whites are characteristically different regarding the prevalence of inadequate sleep over the years. Temporal changes in estimates of inadequate sleep seem dependent upon individuals' race/ethnicity.

Case-control study of breast cancer in India: Role of PERIOD3 clock gene length polymorphism and chronotype.

BACKGROUND: This study examined a PERIOD3 (PER3) gene variable number tandem repeat polymorphism and chronotype as potential BrCA risk factors among Indian women. METHODS: This case-control study included sporadic, histologically confirmed BrCA cases (n = 255) and controls (n = 249) from India with data collection from 2010-2012. RESULTS: Women with the 4/5 or 5/5 PER3 genotype had a nonstatistically significant 33% increased odds of BrCA. Cases were more likely to have a morning (OR = 2.43, 95% CI = 1.23-4.81) or evening (OR = 2.55, 95% CI = 1.19-5.47) chronotype. CONCLUSIONS: Findings are consistent with the possibility that extremes in chronotype may elicit circadian desynchronization, resulting in increased BrCA susceptibility.

Effects of exercise training on sleep apnea: a meta-analysis.

BACKGROUND: Several studies have shown a favorable effect of supervised exercise training on obstructive sleep apnea (OSA). This meta-analysis was conducted to analyze the data from these studies on the severity of OSA (primary outcome) in adults. Secondary outcomes of interest included body mass index (BMI), sleep efficiency, daytime sleepiness and cardiorespiratory fitness. METHODS: Two independent reviewers searched PubMed and Embase (from inception to March 6, 2013) to identify studies on the effects of supervised exercise training in adults with OSA. Pre- and postexercise training data on our primary and secondary outcomes were extracted. RESULTS: A total of 5 studies with 6 cohorts that enrolled a total of 129 study participants met the inclusion criteria. The pooled estimate of mean pre- to postintervention (exercise) reduction in AHI was −6.27 events/h (95 % confidence interval [CI] -8.54 to -3.99; p < 0.001). The pooled estimates of mean changes in BMI, sleep efficiency, Epworth sleepiness scale and VO2 peak were -1.37 (95 % CI −2.81 to 0.07; p = 0.06), 5.75 % (95 % CI 2.47-9.03; p = 0.001), -3.3 (95 % CI -5.57 to -1.02; p = 0.004), and 3.93 mL/kg/min (95 % CI 2.44-5.42; p < 0.001), respectively. CONCLUSIONS: This meta-analysis shows a statistically significant effect of exercise in reducing the severity of sleep apnea in patients with OSA with minimal changes in body weight. Additionally, the significant effects of exercise on cardiorespiratory fitness, daytime sleepiness, and sleep efficiency indicate the potential value of exercise in the management of OSA.

Delaying early morning workouts to protect sleep in two-a-day athletes.

Two-a-day training is common for endurance athletes with training sessions typically beginning at 6 a.m. and 3 p.m. or 4 p.m. However, the early morning workouts could contribute to significant sleep loss, especially for night owls. Chronic sleep loss over a season could result in impaired performance, as well as an increased risk of physical and mental illness. It is hypothesized that shifting the early morning workout to later in the day could have beneficial effects for these athletes. A number of obstacles could make this hypothesis difficulty to test and implement. However, such a change could have dramatic benefits for some athletes.

Sleep, psychological health, and physical activity level in patients with hypertension.

The aim of this study was to compare sleep, daytime sleepiness, and psychological health in physically active versus inactive patients with hypertension. A cross-sectional design included thirty-seven participants (ACTIVE, n = 15; INACTIVE, n = 22). Sleep was assessed by polysomnography, the Pittsburgh Sleep Quality Index (PSQI) and a one-week daily sleep diary. The sleepiness was assessed with the Epworth Sleepiness Scale and the psychological health was assessed with the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Profile of Mood States (POMS). Habitual physical activity was assessed with 7 day-step counts recorded by a pedometer and questionnaire. Significantly lower PSQI score (mean ± S.D.; 7.3 ± 3.4 vs 10.1 ± 3.6) and daytime sleepiness (8.7 ± 4.5 vs. 11.9 ± 4.4) were found in the physically active versus inactive participants, respectively. In addition, higher PSQI-total sleep time (6.9 ± 1.3 vs 5.6 ± 1.1) and vigor/activity (19.7 ± 3.9 vs 16.0 ± 3.9), and lower depressed mood on the POMS scale (8.2 ± 7.9 vs 13.8 ± 10.0) and lower POMS total mood disturbance (21.0 ± 27.0 vs 43.5 ± 32.5) were observed in the active participants compared with the inactive participants. Combining data across both groups, leisure time sport participation correlated negatively with PSQI (r = -0.35; p < 0.05) and BDI (r = -0.42; p < 0.05), and positively with POMS-vigor/activity (r = 0.43; p < 0.05). The results showed regular physical activity was associated with better sleep and psychological health in patients with hypertension.

Association of the Period3 clock gene length polymorphism with salivary cortisol secretion among police officers.

OBJECTIVE: This study evaluated whether measures of waking or diurnal cortisol secretion, or self-reported psychological disturbances differed among police officers with a Period3 (PER3) clock gene length polymorphism. METHODS: The cortisol awakening response was characterized via the area under the salivary cortisol curve with respect to the increase (AUCI) or total waking cortisol (AUCG). Diurnal cortisol measures included the slope of diurnal cortisol and the diurnal AUCG. Psychological disturbances were characterized using the Center for Epidemiologic Studies Depression Scale, Impact of Events Scale, and Life Events Scale. RESULTS: Officers with a 4/5 or 5/5 genotype had higher awakening AUCG and greater diurnal cortisol AUCG levels compared to officers with the 4/4 genotype. Among those working more afternoon or night shifts, waking AUCI and AUCG were greater among officers with a 4/5 or 5/5 genotype compared to the 4/4 referents. CONCLUSION: Cortisol secretion was modified among police officers with different PER3 VNTR clock gene variants.

Exercise as an Adjunct Treatment to Cognitive Behavior Therapy for Insomnia.

The question that guided this review is whether exercise can add to the improvements in insomnia in patients treated with cognitive behavioral therapy for insomnia (CBT-I). CBT-I has long been recommended as the first-line treatment of chronic insomnia. However, CBT-I is not effective for as many as 30% to 40% of patients with insomnia. There is accumulating evidence for positive effects on insomnia following acute and chronic exercise. However, to the best of our knowledge, the effects of CBT-I combined with exercise have not been explored in clinical trials. In this article, we develop a rationale for combining CBT-I with exercise.

Medium- and Long-Term Effects of Insomnia Severity and Circadian Preference on Pain and Emotional Distress Among Individuals With Chronic Pain.

Studies have identified insomnia as having significant influence on chronic pain. A rising body of research has also underscored the association between eveningness and chronic pain. However, co-assessment of insomnia and eveningness in the context of chronic pain adjustment has been limited. The present study sought to investigate the effects of insomnia and eveningness on pain severity, pain interference, and emotional distress (ie, depressive and anxiety symptoms) over nearly 2 years among adults with chronic pain in the U.S. Adults with chronic pain (N = 884) were surveyed 3 times via Amazon's MTurk online crowdsourcing platform: baseline, 9-month follow-up, and 21-month follow-up. Path analysis was conducted to examine the effects of baseline insomnia severity (Insomnia Severity Index) and eveningness (Morningness and Eveningness Questionnaire), as well as their moderating effects on outcomes. Controlling for select sociodemographic variables and baseline outcome levels, greater insomnia severity at baseline was associated with worsening of all of the pain-related outcomes at 9-month follow-up, and pain interreference and emotional distress at 21-month follow-up. We did not find evidence that evening types are at a higher risk of experiencing worsening pain-related outcomes over time compared to morning and intermediate types. There were also no significant insomnia severity and eveningness moderation effects on any outcome. Our findings suggest that insomnia is a more robust predictor of changes in pain-related outcomes as compared to eveningness. Treatment of insomnia can be important in chronic pain management. Future studies should evaluate the role of circadian misalignment on pain using more accurate biobehavioral makers. PERSPECTIVE: This study examined the effects of insomnia and eveningness on pain and emotional distress in a large sample of individuals with chronic pain. Insomnia severity is a stronger predictor of changes in pain and emotional distress than eveningness, highlighting insomnia as an important clinical target for chronic pain management.