Jamie Zeitzer

All Publications

• Beyond phase shifting: Targeting circadian amplitude for light interventions in humans. Sleep Walch, O., Tavella, F., Zeitzer, J. M., Lok, R. 2024

  View details for DOI 10.1093/sleep/zsae247

  View details for PubMedID 39435852

• Perils of the nighttime: Impact of behavioral timing and preference on mental health in 73,888 community-dwelling adults. Psychiatry research Lok, R., Weed, L., Winer, J., Zeitzer, J. M. 2024; 337: 115956

  Abstract

  Mental health is independently influenced by the inclination to sleep at specific times (chronotype) and the actual sleep timing (behavior). Chronotype and timing of actual sleep are, however, often misaligned. This study aims to determine how chronotype, sleep timing, and the alignment between the two impact mental health. In a community-dwelling cohort of middle- and older-aged adults (UK Biobank, n = 73,888), we examined the impact of chronotype (questionnaire-based), the timing of behavior (determined with 7-day accelerometry), and the alignment between the two on mental, behavioral, neurodevelopmental disorders (MBN), depression, and anxiety, as assessed through ICD-10 codes. As compared to morning types with early behavior (aligned), morning types with late behavior (misaligned) had an increased risk of having MBN, depression, and anxiety (p's<0.001). As compared to evening-types with late behavior (aligned), however, evening-types with early behavior (misaligned) had a decreased risk of depression (p < 0.01), with a trend for MBN (p = 0.04) and anxiety (p = 0.05). Longitudinal analyses, in which the likelihood of developing de novo mental health disorders was associated with chronotype, behavioral timing, and alignment between the two, confirmed cross-sectional findings. To age healthily, individuals should start sleeping before 1AM, despite chronobiological preferences.

  View details for DOI 10.1016/j.psychres.2024.115956

  View details for PubMedID 38763081

• The utility of sleep wearables - well, that depends. Sleep Zeitzer, J. M. 2024

  View details for DOI 10.1093/sleep/zsae019

  View details for PubMedID 38266044

• The Negative Effects of Travel on Student Athletes Through Sleep and Circadian Disruption. Journal of biological rhythms Heller, H. C., Herzog, E., Brager, A., Poe, G., Allada, R., Scheer, F., Carskadon, M., de la Iglesia, H. O., Jang, R., Montero, A., Wright, K., Mouraine, P., Walker, M. P., Goel, N., Hogenesch, J., Van Gelder, R. N., Kriegsfeld, L., Mah, C., Colwell, C., Zeitzer, J., Grandner, M., Jackson, C. L., Roxanne Prichard, J., Kay, S. A., Paul, K. 2023: 7487304231207330

  Abstract

  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.

  View details for DOI 10.1177/07487304231207330

  View details for PubMedID 37978840

• Moving time zones in a flash with light therapy during sleep. Scientific reports Lok, R., Duran, M., Zeitzer, J. M. 2023; 13 (1): 14458

  Abstract

  In humans, exposure to continuous light is typically used to change the timing of the circadian clock. This study examines the efficiency of a sequence of light flashes ("flash therapy") applied during sleep to shift the clock. Healthy participants (n = 10) took part in two 36-h laboratory stays, receiving a placebo (goggles, no light) during one visit and the intervention (goggles, 2-ms flashes broad-spectrum light for 60 min, delivered every 15 s, starting 30 min after habitual sleep onset) during the other. Circadian phase shift was assessed with changes in salivary dim light melatonin onset (DLMO). Sleep, measured with polysomnography, was analyzed to assess changes in sleep architecture and spectral power. After 1 h of flashes, DLMO showed a substantial delay (1.13 ± 1.27 h) compared to placebo (12 ± 20 min). Two individuals exhibited very large shifts of 6.4 and 3.1 h. There were no substantive differences in sleep architecture, but some evidence for greater instability in sleep. 1 h of flash therapy during sleep evokes large changes in circadian timing, up to 6 h, and does so with only minimal, if any, impact on sleep. Flash therapy may offer a practical option to delay the circadian clock in shift workers and jet travelers.

  View details for DOI 10.1038/s41598-023-41742-w

  View details for PubMedID 37660233

  View details for PubMedCentralID PMC10475014

• Impact of daytime spectral tuning on cognitive function. Journal of photochemistry and photobiology. B, Biology Lok, R., Joyce, D. S., Zeitzer, J. M. 2022; 230: 112439

  Abstract

  Light at night can improve alertness and cognition. Exposure to daytime light, however, has yielded less conclusive results. In addition to direct effects, daytime light may also mitigate the impact of nocturnal light exposure on alertness. To examine the impact of daytime lighting on daytime cognitive performance, and evening alertness, we studied nine healthy individuals using a within subject crossover design. On four visits, participants were exposed to one of four lighting conditions for 10h (dim fluorescent, room fluorescent, broad-spectrum LED, standard white LED; the latter three conditions were matched for 100lx) followed by an exposure to bright evening light. Cognitive performance, subjective and objective measures of alertness were regularly obtained. While daytime alertness was not impacted by light exposure, the broad-spectrum LED light improved several aspects of daytime cognition. The impact of evening light on alertness was not mitigated by the pre-exposure to different daytime lighting conditions. Results suggest that daytime exposure to white light with high melanopic efficacy has the potential to improve daytime cognitive function and that such improvements are likely to be direct rather than a consequence of light-induced changes in alertness.

  View details for DOI 10.1016/j.jphotobiol.2022.112439

  View details for PubMedID 35398657

• Objective underpinnings of self-reported sleep quality in middle-aged and older adults: the importance of N2 and wakefulness. Biological psychology Lok, R., Chawra, D., Hon, F., Ha, M., Kaplan, K. A., Zeitzer, J. M. 2022: 108290

  Abstract

  STUDY OBJECTIVES: The measurable aspects of brain function (polysomnography, PSG) that are correlated with sleep satisfaction are poorly understood. Using recent developments in automated sleep scoring, which remove the within- and between-rater error associated with human scoring, we examine whether PSG measures are associated with sleep satisfaction.DESIGN AND SETTING: A single night of PSG data was compared to contemporaneously collected measures of sleep satisfaction with Random Forest regressions. Whole and partial night PSG data were scored using a novel machine learning algorithm.PARTICIPANTS: Community-dwelling adults (N=3,165) who participated in the Sleep Heart Health Study.INTERVENTIONS: None MEASUREMENTS AND RESULTS: Models explained 30% of sleep depth and 27% of sleep restfulness, with a similar top four predictors: minutes of N2 sleep, sleep efficiency, age, and minutes of wake after sleep onset (WASO). With increasing self-reported sleep quality, there was a progressive increase in N2 and decrease in WASO of similar magnitude, without systematic changes in N1, N3 or REM sleep. In comparing those with the best and worst self-reported sleep satisfaction, there was a range of approximately 30minutes more N2, 30minutes less WASO, an improvement of sleep efficiency of 7-8%, and an age span of 3-5 years. Examination of sleep most proximal to morning awakening revealed no greater explanatory power than the whole-night data set.CONCLUSIONS: Higher N2 and concomitant lower wake is associated with improved sleep satisfaction. Interventions that specifically target these may be suitable for improving the self-reported sleep experience.

  View details for DOI 10.1016/j.biopsycho.2022.108290

  View details for PubMedID 35192907

• The neurobiological underpinning of the circadian wake signal. Biochemical pharmacology Zeitzer, J. M. 2020: 114386

  Abstract

  The circadian wake drive is a mathematic representation of the observed increased propensity to stay awake late in the day, peaking in the hours just before anticipated bed time. It has been called the "forbidden zone" due to the difficulty in initiating sleep during this time and is responsible for the problems initiating sleep when traveling eastward, for maintaining daytime sleep in shift workers, and for initiating sleep in some individuals with insomnia. Evidence culled from studies in individuals with narcolepsy, who lack production of hypocretin (orexin) neuropeptides, as well as a primate model of human wake consolidation and pharmacologic studies of hypocretin antagonists indicate that hypocretin-1 may be the physiologic instantiation of the circadian wake drive. This review will discuss the evidence in support of this hypothesis.

  View details for DOI 10.1016/j.bcp.2020.114386

  View details for PubMedID 33359009

• Human-centric lighting: Myth, magic or metaphor? LIGHTING RESEARCH & TECHNOLOGY Houser, K. W., Boyce, P. R., Zeitzer, J. M., Herf, M. 2020

  View details for DOI 10.1177/1477153520958448

  View details for Web of Science ID 000578226600001

• Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers: A Randomized Clinical Trial. JAMA network open Zeitzer, J. M., Joyce, D. S., McBean, A., Quevedo, Y. L., Hernandez, B., Holty, J. 2020; 3 (6): e206614

  Abstract

  Importance: Many shift workers have difficulty sleeping during the daytime owing to an inappropriately timed circadian drive for wakefulness.Objective: To determine whether a dual hypocretin receptor antagonist would enable shift workers to have more daytime sleep.Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 2 weeks of baseline data and 3 weeks of intervention data, from March 2016 to December 2018. Individuals were recruited through poster advertisements in the broader San Francisco Bay area in California. From an initial voluntary recruitment cohort of 38 shift workers, 19 individuals with self-reported difficulty sleeping during the daytime following night work shift were included. Data were analyzed from Janaury to March 2019.Interventions: 1 week of 10 mg suvorexant or placebo, titrated upward to 20 mg suvorexant or placebo for 2 additional weeks.Main Outcomes and Measures: Objective (ie, actigraphy) and subjective (ie, sleep logs) measures of sleep.Results: Among 19 participants who completed the study (mean [SD] age, 37.7 [11.1] years; 13 [68%] men), 8 participants (42%) were assigned to the suvorexant group and 11 participants (58%) were assigned to the placebo group. Compared with individuals in the placebo group, individuals in the suvorexant group increased their objective total sleep time by a mean (SE) of 1.04 (0.53) hours (P=.05) at the end of 1 week of 10-mg doses and by 2.16 (0.75) hours (P=.004) by the end of the 2 weeks of 20-mg doses. Subjective sleep was similarly improved as, compared with the placebo group, individuals in the suvorexant group increased their subjective total sleep time by a mean (SE) of 2.08 (0.47) hours (P<.001) at the end of 1 week of 10-mg doses and by 2.97 (0.56) hours (P<.001) by the end of the 2 weeks of 20-mg doses. Physician ratings of daytime sleep aligned with these measures, as there was no change in the placebo group and a much improved change in the suvorexant group. No adverse events were reported in the suvorexant group.Conclusions and Relevance: This pilot study found that the use of a dual hypocretin receptor antagonist in shift workers under real-world conditions resulted in more than 2 extra hours of daytime sleep per episode. Future research should confirm this pilot finding in a larger sample size and examine whether, over the long term, use of this medication has a concomitant improvement in medical and psychiatric health as well as workplace performance and safety.Trial Registration: ClinicalTrials.gov Identifier: NCT02491788.

  View details for DOI 10.1001/jamanetworkopen.2020.6614

  View details for PubMedID 32484552

• Effect of Light Flashes vs Sham Therapy During Sleep With Adjunct Cognitive Behavioral Therapy on Sleep Quality Among Adolescents: A Randomized Clinical Trial. JAMA network open Kaplan, K. A., Mashash, M., Williams, R., Batchelder, H., Starr-Glass, L., Zeitzer, J. M. 2019; 2 (9): e1911944

  Abstract

  Importance: Owing to biological, behavioral, and societal factors, sleep duration in teenagers is often severely truncated, leading to pervasive sleep deprivation.Objective: To determine whether a novel intervention, using both light exposure during sleep and cognitive behavioral therapy (CBT), would increase total sleep time in teenagers by enabling them to go to sleep earlier than usual.Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial, conducted between November 1, 2013, and May 31, 2016, among 102 adolescents enrolled full-time in grades 9 to 12, who expressed difficulty going to bed earlier and waking up early enough, was composed of 2 phases. In phase 1, participants were assigned to receive either 3 weeks of light or sham therapy and were asked to try to go to sleep earlier. In phase 2, participants received 4 brief CBT sessions in addition to a modified light or sham therapy. All analyses were performed on an intent-to-treat basis.Interventions: Light therapy consisted of receiving a 3-millisecond light flash every 20 seconds during the final 3 hours of sleep (phase 1) or final 2 hours of sleep (phase 2). Sham therapy used an identical device, but delivered 1 minute of light pulses (appearing in 20-second intervals, for a total of 3 pulses) per hour during the final 3 hours of sleep (phase 1) or 2 hours of sleep (phase 2). Light therapy occurred every night during the 4-week intervention. Cognitive behavioral therapy consisted of four 50-minute in-person sessions once per week.Main Outcomes and Measures: Primary outcome measures included diary-based sleep times, momentary ratings of evening sleepiness, and subjective measures of sleepiness and sleep quality.Results: Among the 102 participants (54 female [52.9%]; mean [SD] age, 15.6 [1.1] years), 72 were enrolled in phase 1 and 30 were enrolled in phase 2. Mixed-effects models revealed that light therapy alone was inadequate in changing the timing of sleep. However, compared with sham therapy plus CBT alone, light therapy plus CBT significantly moved sleep onset a mean (SD) of 50.1 (27.5) minutes earlier and increased nightly total sleep time by a mean (SD) of 43.3 (35.0) minutes. Light therapy plus CBT also resulted in a 7-fold greater increase in bedtime compliance than that observed among participants receiving sham plus CBT (mean [SD], 2.21 [3.91] vs 0.29 [0.76]), as well as a mean 0.55-point increase in subjective evening sleepiness as compared with a mean 0.48-point decrease in participants receiving sham plus CBT as measured on a 7-point sleepiness scale.Conclusions and Relevance: This study found that light exposure during sleep, in combination with a brief, motivation-focused CBT intervention, was able to consistently move bedtimes earlier and increase total sleep time in teenagers. This type of passive light intervention in teenagers may lead to novel therapeutic applications.Trial Registration: ClinicalTrials.gov identifier: NCT01406691.

  View details for DOI 10.1001/jamanetworkopen.2019.11944

  View details for PubMedID 31553469

• When is a proxy not a proxy? The foibles of studying non-image forming light. The Journal of physiology Zeitzer, J. M. 2018; 596 (11): 2029–30

  View details for PubMedID 29717490

• When is a proxy not a proxy? The foibles of studying non-image forming light JOURNAL OF PHYSIOLOGY-LONDON Zeitzer, J. M. 2018; 596 (11): 2029-2030

  View details for DOI 10.1113/JP276076

  View details for Web of Science ID 000434178300002

• Daily Patterns of Accelerometer Activity Predict Changes in Sleep, Cognition, and Mortality in Older Men. journals of gerontology. Series A, Biological sciences and medical sciences Zeitzer, J. M., Blackwell, T., Hoffman, A. R., Cummings, S., Ancoli-Israel, S., Stone, K. 2017

  Abstract

  There is growing interest in the area of "wearable tech" and its relationship to health. A common element of many of these devices is a triaxial accelerometer that can yield continuous information on gross motor activity levels; how such data might predict changes in health is less clear.We examined accelerometry data from 2,976 older men who were part of the Osteoporotic Fractures in Men (MrOS) study. Using a shape-naive technique, functional principal component analysis, we examined the patterns of motor activity over the course of 4-7 days and determined whether these patterns were associated with changes in polysomnographic-determined sleep and cognitive function (Trail Making Test-Part B [Trails B], Modified Mini-Mental State Examination [3MS]), as well as mortality over 6.5-8 years of follow-up.In comparing baseline to 6.5 years later, multivariate modeling indicated that low daytime activity at baseline was associated with worsening of sleep efficiency (p < .05), more wake after sleep onset (p < .05), and a decrease in cognition (Trails B; p < .001), as well as a 1.6-fold higher rate of all-cause mortality (hazard ratio = 1.64 [1.34-2.00]). Earlier wake and bed times were associated with a decrease in cognition (3MS; p < .05). Having a late afternoon peak in activity was associated with a 1.4-fold higher rate of all-cause mortality (hazard ratio = 1.46 [1.21-1.77]). Those having a longer duration of their daytime activity with a bimodal activity pattern also had over a 1.4-fold higher rate of cardiovascular-related mortality (hazard ratio = 1.42 [1.02-1.98]).Patterns of daily activity may be useful as predictive biomarkers for changes in clinically relevant outcomes, including mortality and changes in sleep and cognition in older men.

  View details for DOI 10.1093/gerona/glw250

  View details for PubMedID 28158467

• When a gold standard isn't so golden: Lack of prediction of subjective sleep quality from sleep polysomnography. Biological psychology Kaplan, K. A., Hirshman, J., Hernandez, B., Stefanick, M. L., Hoffman, A. R., Redline, S., Ancoli-Israel, S., Stone, K., Friedman, L., Zeitzer, J. M. 2017; 123: 37-46

  Abstract

  Reports of subjective sleep quality are frequently collected in research and clinical practice. It is unclear, however, how well polysomnographic measures of sleep correlate with subjective reports of prior-night sleep quality in elderly men and women. Furthermore, the relative importance of various polysomnographic, demographic and clinical characteristics in predicting subjective sleep quality is not known. We sought to determine the correlates of subjective sleep quality in older adults using more recently developed machine learning algorithms that are suitable for selecting and ranking important variables.Community-dwelling older men (n=1024) and women (n=459), a subset of those participating in the Osteoporotic Fractures in Men study and the Study of Osteoporotic Fractures study, respectively, completed a single night of at-home polysomnographic recording of sleep followed by a set of morning questions concerning the prior night's sleep quality. Questionnaires concerning demographics and psychological characteristics were also collected prior to the overnight recording and entered into multivariable models. Two machine learning algorithms, lasso penalized regression and random forests, determined variable selection and the ordering of variable importance separately for men and women.Thirty-eight sleep, demographic and clinical correlates of sleep quality were considered. Together, these multivariable models explained only 11-17% of the variance in predicting subjective sleep quality. Objective sleep efficiency emerged as the strongest correlate of subjective sleep quality across all models, and across both sexes. Greater total sleep time and sleep stage transitions were also significant objective correlates of subjective sleep quality. The amount of slow wave sleep obtained was not determined to be important.Overall, the commonly obtained measures of polysomnographically-defined sleep contributed little to subjective ratings of prior-night sleep quality. Though they explained relatively little of the variance, sleep efficiency, total sleep time and sleep stage transitions were among the most important objective correlates.

  View details for DOI 10.1016/j.biopsycho.2016.11.010

  View details for PubMedID 27889439

  View details for PubMedCentralID PMC5292065

• Harnessing the Web for Population-Scale Physiological Sensing: A Case Study of Sleep and Performance Althoff, T., Horvitz, E., White, R. W., Zeitzer, J., ACM ASSOC COMPUTING MACHINERY. 2017: 113-122

  View details for DOI 10.1145/3038912.3052637

  View details for Web of Science ID 000461544900015

• Aberrant nocturnal cortisol and disease progression in women with breast cancer BREAST CANCER RESEARCH AND TREATMENT Zeitzer, J. M., Nouriani, B., Rissling, M. B., Sledge, G. W., Kaplan, K. A., Aasly, L., Palesh, O., Jo, B., Neri, E., Dhabhar, F. S., Spiegel, D. 2016; 158 (1): 43-50

  Abstract

  While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p < 0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r = -0.30, p = 0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

  View details for DOI 10.1007/s10549-016-3864-2

  View details for Web of Science ID 000379494200005

  View details for PubMedID 27314577

  View details for PubMedCentralID PMC4938753

• Temporal integration of light flashes by the human circadian system JOURNAL OF CLINICAL INVESTIGATION Najjar, R. P., Zeitzer, J. M. 2016; 126 (3): 938-947

  Abstract

  Beyond image formation, the light that is detected by retinal photoreceptors influences subcortical functions, including circadian timing, sleep, and arousal. The physiology of nonimage-forming (NIF) photoresponses in humans is not well understood; therefore, the development of therapeutic interventions based on this physiology, such as bright light therapy to treat chronobiological disorders, remains challenging.Thirty-nine participants were exposed to 60 minutes of either continuous light (n = 8) or sequences of 2-millisecond light flashes (n = 31) with different interstimulus intervals (ISIs; ranging from 2.5 to 240 seconds). Melatonin phase shift and suppression, along with changes in alertness and sleepiness, were assessed.We determined that the human circadian system integrates flash sequences in a nonlinear fashion with a linear rise to a peak response (ISI = 7.6 ± 0.53 seconds) and a power function decrease following the peak of responsivity. At peak ISI, flashes were at least 2-fold more effective in phase delaying the circadian system as compared with exposure to equiluminous continuous light 3,800 times the duration. Flashes did not change melatonin concentrations or alertness in an ISI-dependent manner.We have demonstrated that intermittent light is more effective than continuous light at eliciting circadian changes. These findings cast light on the phenomenology of photic integration and suggest a dichotomous retinohypothalamic network leading to circadian phase shifting and other NIF photoresponses. Further clinical trials are required to judge the practicality of light flash protocols.Clinicaltrials.gov NCT01119365.National Heart, Lung, and Blood Institute (1R01HL108441-01A1) and Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center.

  View details for DOI 10.1172/JCI82306

  View details for Web of Science ID 000371193700015

  View details for PubMedID 26854928

  View details for PubMedCentralID PMC4767340

• Real life trumps laboratory in matters of public health. Proceedings of the National Academy of Sciences of the United States of America Zeitzer, J. M. 2015; 112 (13): E1513

  View details for DOI 10.1073/pnas.1500717112

  View details for PubMedID 25762078

  View details for PubMedCentralID PMC4386401

• Millisecond flashes of light phase delay the human circadian clock during sleep. Journal of biological rhythms Zeitzer, J. M., Fisicaro, R. A., Ruby, N. F., Heller, H. C. 2014; 29 (5): 370-376

  Abstract

  The human circadian timing system is most sensitive to the phase-shifting effects of light during the biological nighttime, a time at which humans are most typically asleep. The overlap of sleep with peak sensitivity to the phase-shifting effects of light minimizes the effectiveness of using light as a countermeasure to circadian misalignment in humans. Most current light exposure treatments for such misalignment are mostly ineffective due to poor compliance and secondary changes that cause sleep deprivation. Using a 16-day, parallel group design, we examined whether a novel sequence of light flashes delivered during sleep could evoke phase changes in the circadian system without disrupting sleep. Healthy volunteers participated in a 2-week circadian stabilization protocol followed by a 2-night laboratory stay. During the laboratory session, they were exposed during sleep to either darkness (n = 7) or a sequence of 2-msec light flashes given every 30 sec (n = 6) from hours 2 to 3 after habitual bedtime. Changes in circadian timing (phase) and micro- and macroarchitecture of sleep were assessed. Subjects exposed to the flash sequence during sleep exhibited a delay in the timing of their circadian salivary melatonin rhythm compared with the control dark condition (p < 0.05). Confirmation that the flashes penetrated the eyelids is presented by the occurrence of an evoked response in the EEG. Despite the robust effect on circadian timing, there were no large changes in either the amount or spectral content of sleep (p values > 0.30) during the flash stimulus. Exposing sleeping individuals to 0.24 sec of light spread over an hour shifted the timing of the circadian clock and did so without major alterations to sleep itself. While a greater number of matched subjects and more research will be necessary to ascertain whether these light flashes affect sleep, our data suggest that this type of passive phototherapy might be developed as a useful treatment for circadian misalignment in humans.

  View details for DOI 10.1177/0748730414546532

  View details for PubMedID 25227334

• Millisecond Flashes of Light Phase Delay the Human Circadian Clock during Sleep JOURNAL OF BIOLOGICAL RHYTHMS Zeitzer, J. M., Fisicaro, R. A., Ruby, N. F., Heller, H. C. 2014; 29 (5): 370-376

  Abstract

  The human circadian timing system is most sensitive to the phase-shifting effects of light during the biological nighttime, a time at which humans are most typically asleep. The overlap of sleep with peak sensitivity to the phase-shifting effects of light minimizes the effectiveness of using light as a countermeasure to circadian misalignment in humans. Most current light exposure treatments for such misalignment are mostly ineffective due to poor compliance and secondary changes that cause sleep deprivation. Using a 16-day, parallel group design, we examined whether a novel sequence of light flashes delivered during sleep could evoke phase changes in the circadian system without disrupting sleep. Healthy volunteers participated in a 2-week circadian stabilization protocol followed by a 2-night laboratory stay. During the laboratory session, they were exposed during sleep to either darkness (n = 7) or a sequence of 2-msec light flashes given every 30 sec (n = 6) from hours 2 to 3 after habitual bedtime. Changes in circadian timing (phase) and micro- and macroarchitecture of sleep were assessed. Subjects exposed to the flash sequence during sleep exhibited a delay in the timing of their circadian salivary melatonin rhythm compared with the control dark condition (p < 0.05). Confirmation that the flashes penetrated the eyelids is presented by the occurrence of an evoked response in the EEG. Despite the robust effect on circadian timing, there were no large changes in either the amount or spectral content of sleep (p values > 0.30) during the flash stimulus. Exposing sleeping individuals to 0.24 sec of light spread over an hour shifted the timing of the circadian clock and did so without major alterations to sleep itself. While a greater number of matched subjects and more research will be necessary to ascertain whether these light flashes affect sleep, our data suggest that this type of passive phototherapy might be developed as a useful treatment for circadian misalignment in humans.

  View details for DOI 10.1177/0748730414546532

  View details for Web of Science ID 000344267300006

• Response of the Human Circadian System to Millisecond Flashes of Light PLOS ONE Zeitzer, J. M., Ruby, N. F., Fisicaro, R. A., Heller, H. C. 2011; 6 (7)

  Abstract

  Ocular light sensitivity is the primary mechanism by which the central circadian clock, located in the suprachiasmatic nucleus (SCN), remains synchronized with the external geophysical day. This process is dependent on both the intensity and timing of the light exposure. Little is known about the impact of the duration of light exposure on the synchronization process in humans. In vitro and behavioral data, however, indicate the circadian clock in rodents can respond to sequences of millisecond light flashes. In a cross-over design, we tested the capacity of humans (n = 7) to respond to a sequence of 60 2-msec pulses of moderately bright light (473 lux) given over an hour during the night. Compared to a control dark exposure, after which there was a 3.5±7.3 min circadian phase delay, the millisecond light flashes delayed the circadian clock by 45±13 min (p<0.01). These light flashes also concomitantly increased subjective and objective alertness while suppressing delta and sigma activity (p<0.05) in the electroencephalogram (EEG). Our data indicate that phase shifting of the human circadian clock and immediate alerting effects can be observed in response to brief flashes of light. These data are consistent with the hypothesis that the circadian system can temporally integrate extraordinarily brief light exposures.

  View details for DOI 10.1371/journal.pone.0022078

  View details for Web of Science ID 000292657200045

  View details for PubMedID 21760955

  View details for PubMedCentralID PMC3132781

• Impact Of Time Of Day On Neuromuscular Performance Of The Star Excursion Balance Test In Young Women Weed, L., Thompson, S., Kraus, E., Delp, S., Zeitzer, J. LIPPINCOTT WILLIAMS & WILKINS. 2024: 257-258

  View details for Web of Science ID 001315123201146

• How many days are enough? Sleep-wake timing regularity and fragmentation scores change with the number of days included. Journal of sleep research Lok, R., Suh, S., Rue, S., Weed, L., Zeitzer, J. M. 2024: e14332

  Abstract

  The duration of sleep data collection from actigraphy is often influenced by practical factors (e.g. workdays versus non-workdays), but the impact of the variation of duration on outcome measures of interest has not been well explored. This study investigates the effect of the duration of actigraphy measurement on non-parametric measures of 24-hr sleep-wake rhythms. We examined regularity inter-daily stability and fragmentation intra-daily variation over 14 days or the first 7 days in participants (n = 41) undergoing evaluation for sleep disorders. Bland-Altman plots assessed the impact of fewer than 14 or 7 days, respectively, on inter-daily stability and intra-daily variation scores. Intra-daily variation values were also calculated for each day and compared with the 14-day intra-daily variation. Compared with the entire 14-day period, using shorter durations (< 7 days) led to a higher estimated bias and increased variance in the limits of agreement for inter-daily stability. Intra-daily variation values showed increased variation in the limits of agreement with fewer days. Similar trends were observed when comparing shorter actigraphy periods 3 or 5 days-7 days. Daily intra-daily variation calculations indicate that individuals with higher daily fragmentation experienced more pronounced day-to-day fragmentation and greater variability in the degree of fragmentation, in a linear association between daily intra-daily variation standard deviation and 14-day intra-daily variation values. Our data indicate that a minimum of 7 full days of actigraphy is recommended to reduce measurement errors, and intra-daily variation and inter-daily stability derived from less than 7 days cannot be compared with those from more than 7 days without significant error.

  View details for DOI 10.1111/jsr.14332

  View details for PubMedID 39317644

• A Deep Transfer Learning Approach for Sleep Stage Classification and Sleep Apnea Detection Using Wrist-Worn Consumer Sleep Technologies. IEEE transactions on bio-medical engineering Olsen, M., Zeitzer, J. M., Nakase-Richardson, R., Musgrave, V. H., Sorensen, H. B., Mignot, E., Jennum, P. J. 2024; 71 (8): 2506-2517

  Abstract

  Obstructive sleep apnea (OSA) is a common, underdiagnosed sleep-related breathing disorder with serious health implications Objective - We propose a deep transfer learning approach for sleep stage classification and sleep apnea (SA) detection using wrist-worn consumer sleep technologies (CST). Methods - Our model is based on a deep convolutional neural network (DNN) utilizing accelerometers and photo-plethysmography signals from nocturnal recordings. The DNN was trained and tested on internal datasets that include raw data from clinical and wrist-worn devices; external validation was performed on a hold-out test dataset containing raw data from a wrist-worn CST. Results - Training on clinical data improves performance significantly, and feature enrichment through a sleep stage stream gives only minor improvements. Raw data input outperforms feature-based input in CST datasets. The system generalizes well but performs slightly worse on wearable device data compared to clinical data. However, it excels in detecting events during REM sleep and is associated with arousal and oxygen desaturation. We found; cases that were significantly underestimated were characterized by fewer of such event associations. Conclusion - This study showcases the potential of using CSTs as alternate screening solution for undiagnosed cases of OSA. Significance - This work is significant for its development of a deep transfer learning approach using wrist-worn consumer sleep technologies, offering comprehensive validation for data utilization, and learning techniques, ultimately improving sleep apnea detection across diverse devices.

  View details for DOI 10.1109/TBME.2024.3378480

  View details for PubMedID 38498753

• Sleep Composition of Patients With Colorectal Cancer and Their Sleep-Partner Caregivers: Physical Health Correlates of Sleep Diary and Actigraphy Measurements. Psycho-oncology Ting, A., Tsai, T. C., Zeitzer, J. M., Mendez, A., Kim, Y. 2024; 33 (8): e9302

  Abstract

  Disturbed sleep is frequently identified in adult patients with cancer and their caregivers, with detrimental impact on physical health. Less known is the extent to which self-reported and actigraph-measured sleep patterns are similar between patients and their sleep-partner caregivers, and how these different modes of sleep measurements are related to physical health.Patients diagnosed with colorectal cancer and their sleep-partner caregivers (81 dyads) completed a questionnaire for physical functioning and collected saliva samples for seven consecutive days, from which cortisol slope was quantified. Additionally, participants completed a daily sleep diary and wore actigraph for 14 consecutive days, from which sleep duration, sleep onset latency (SOL), and duration of wake after sleep onset (WASO) were calculated.Participants reported sleep patterns that fell within or close to the optimal range, which were similar between patients and their caregivers. Self-reported and actigraph-measured sleep duration had moderate levels of agreement (ICC = 0.604), whereas SOL and WASO had poor agreement (ICC = 0.269). Among patients, longer self-reported WASO was associated with poorer physical health and flatter cortisol slope (p ≤ 0.013). Among caregivers, longer self-reported SOL was associated with poorer physical functioning, actigraph-measured WASO was associated with steeper cortisol slope, and longer self-reported sleep markers studied than actigraph-measured were associated with poorer physical functioning (p ≤ 0.042).Findings suggest that employing multiple assessment modes for sleep and physical health is vital for comprehensive understanding of sleep health. Furthermore, when addressing patients' sleep health, it may be beneficial to include their sleep-partner caregivers who may experience similar disturbed sleep.

  View details for DOI 10.1002/pon.9302

  View details for PubMedID 39123341

• Sleep insufficiency and bedtime irregularity in children with ADHD: A population-based analysis. Sleep medicine Leman, T. Y., Barden, S., Swisher, V. S., Joyce, D. S., Kaplan, K. A., Zeitzer, J. M., Loo, S. K., Ricketts, E. J. 2024; 121: 117-126

  Abstract

  Sleep is impaired in children with attention-deficit/hyperactivity disorder (ADHD). However, population-based examination of indicators of sleep insufficiency and bedtime irregularity is limited. This investigation examined associations between ADHD, weeknight sleep insufficiency, and bedtime irregularity in a nationally-representative child sample, and indicators of these sleep outcomes in ADHD.Parents of children aged 3-17 years with ADHD (n = 7671) were surveyed through the 2020-2021 National Survey of Children's Health. Inverse probability of treatment weighting generated a weighted matched control sample (n = 51,572). Weighted generalized linear models were performed without and with age-stratification to examine associations between ADHD and sleep, adjusting for sociodemographics in the full sample, and between nineteen sociodemographic and clinical variables and sleep in ADHD.Having ADHD was associated with increased odds of sleep insufficiency and bedtime irregularity relative to controls, even after adjusting for sociodemographic variables. In ADHD, older age was associated with lower sleep insufficiency and greater bedtime irregularity. Black race, increased poverty, higher ADHD severity, depression, and increased screen time were associated with greater sleep insufficiency and bedtime irregularity. Adverse childhood experiences (ACEs) were associated with greater sleep insufficiency. Behavioral/conduct problems, female sex, and absence of both ADHD medication use and ASD diagnosis were associated with poorer bedtime irregularity. Age-stratified results are reported in text.Children with ADHD face heightened risk for insufficient sleep and irregular bedtimes. Findings suggest intervention targets (e.g., Black race, poverty, depression, screen time) to improve both sleep insufficiency and bedtime irregularity. Results highlight ACEs and behavioral/conduct problems as targets to improve sleep insufficiency and bedtime regularity, respectively. Age-stratified findings are discussed.

  View details for DOI 10.1016/j.sleep.2024.06.015

  View details for PubMedID 38959718

• DYADIC INVESTIGATION OF POST-TRAUMATIC STRESS SYMPTOMS AND DAILY SLEEP HEALTH IN PATIENTS WITH CANCER AND THEIR CAREGIVERS Tsai, T., Mitchell, H., Zeitzer, J., Ting, A., Laurenceau, J., Spiegel, D., Kim, Y. LIPPINCOTT WILLIAMS & WILKINS. 2024: A182

  View details for Web of Science ID 001290655500443

• The impact of screen use on sleep health across the lifespan: A National Sleep Foundation consensus statement. Sleep health Hartstein, L. E., Mathew, G. M., Reichenberger, D. A., Rodriguez, I., Allen, N., Chang, A. M., Chaput, J. P., Christakis, D. A., Garrison, M., Gooley, J. J., Koos, J. A., Van Den Bulck, J., Woods, H., Zeitzer, J. M., Dzierzewski, J. M., Hale, L. 2024

  Abstract

  To achieve consensus on whether screen-based digital media (1) in general, (2) via prebedtime content, and (3) via prebedtime light impairs sleep health in (a) childhood, (b) adolescence, and (c) adulthood. Furthermore, to address whether employing behavioral strategies and interventions may reduce the potential negative effects of screens on sleep health.The National Sleep Foundation convened a 16-person multidisciplinary expert panel ("Panel"). Panelists met virtually 5 times throughout 2023, during which they followed a modified Delphi RAND/UCLA Appropriateness Method to reach consensus.The Panel conducted a literature review starting with 2209 articles, narrowed down to 522 relevant empirical articles and 52 relevant review articles. The search was refined to include 35 experimental/intervention studies that examined whether there was a causal link between screen-based digital media and sleep. In addition, panelists reviewed 5 recent relevant systematic review articles. After reviewing the summarized current literature, panelists voted on 10 candidate statements about whether screen use impairs sleep health. The Panel met virtually to discuss the results of the first round of votes, which was then followed by a second round of voting, ultimately achieving consensus on 5 out of the 10 statements.The Panel achieved consensus that (1) in general, screen use impairs sleep health among children and adolescents, (2) the content of screen use before sleep impairs sleep health of children and adolescents, and (3) behavioral strategies and interventions may attenuate the negative effects of screen use on sleep health.

  View details for DOI 10.1016/j.sleh.2024.05.001

  View details for PubMedID 38806392

• CIRCADIAN PROTEINS AND CIRCADIAN PHASE ESTIMATION IN HEALTHY ADULTS Specht, A., Saha, P., Cederberg, K., Bueno, F., Arrona-Palacios, A., Pardilla-Delgado, E., Ruiz-Herrera, N., Zitting, K., Kramer, A., Zeitzer, J., Czeisler, C., Duffy, J., Mignot, E. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/sleep/zsae067.0009

  View details for Web of Science ID 001262172000010

• CIRCADIAN REST-ACTIVITY RHYTHM PATTERNS AND PHYSICAL PERFORMANCE IN COMMUNITY-DWELLING OLDER MEN Qiao, Y., Chen, D., Zeitzer, J., Ancoli-Israel, S., Blackwell, T., Bradshaw, P., Posner, A., Redline, S., Tranah, G., Yaffe, K., Stone, K. OXFORD UNIV PRESS INC. 2024

  View details for DOI 10.1093/sleep/zsae067.0001

  View details for Web of Science ID 001262172000002

• ASSOCIATION OF INSOMNIA WITH OBJECTIVE SHORT SLEEP DURATION AND OTHER PHENOTYPES WITH MORTALITY IN OLDER PERSONS Miner, B., Pan, Y., Cho, G., Knauert, M., Yaggi, H., Gill, T., Stone, K., Ensrud, K., Zeitzer, J., Yaffe, K., Doyle, M. OXFORD UNIV PRESS INC. 2024

  View details for Web of Science ID 001262172001280

• PHYSICAL HEALTH CORRELATES OF SUBJECTIVE AND OBJECTIVE SLEEP MARKERS IN PATIENTS WITH CANCER AND THEIR CAREGIVERS Kim, Y., Tsai, T., Ting, A., Zeitzer, J., Ramos, A., Mendez, A. OXFORD UNIV PRESS INC. 2024

  View details for Web of Science ID 001262172001426

• Reconsidering the spectral distribution of light: Do people perceive watts or photons? LIGHTING RESEARCH & TECHNOLOGY Martinsons, C., Behar-Cohen, F., Bergen, T., Blattner, P., Herf, M., Gronfier, C., Houser, K., Jost, S., Tengelin, M., Obein, G., Schlangen, L., Simonot, L., Spitschan, M., Torriglia, A., Zeitzer, J. 2024

  View details for DOI 10.1177/14771535241246060

  View details for Web of Science ID 001216872300001

• Reconsidering the spectral distribution of light: Do people perceive watts or photons? Lighting research & technology (London, England : 2001) Martinsons, C., Behar-Cohen, F., Bergen, T., Blattner, P., Herf, M., Gronfier, C., Houser, K., Jost, S., Tengelin, M. N., Obein, G., Schlangen, L., Simonot, L., Spitschan, M., Torriglia, A., Zeitzer, J. 2024: 14771535241246060

  Abstract

  The spectral distribution is a fundamental property of non-monochromatic optical radiation. It is commonly used in research and practical applications when studying how light interacts with matter and living organisms, including humans. In the field of lighting, mis-conceptions about the spectral distribution of light are responsible for unfounded claims, which pervade the scientific and technical communities. Starting from the definition of the spectral distribution, this paper describes the ambiguities and errors associated with a purely graphical analysis of the spectral distribution. It also emphasizes the importance of considering the particle nature of light in research involving both visual and non-visual effects, which implies using the spectral distribution expressed in the photon system of units, a system that has been seldom used in lighting research for historical reasons. The authors encourage lighting engineers and researchers to determine which system is best suited to their work and then proceed with the correct use of spectral distributions and of spectral weighting functions for applications involving optical radiation.

  View details for DOI 10.1177/14771535241246060

  View details for PubMedID 39404668

  View details for PubMedCentralID PMC7616565

• Impaired 24-h activity patterns are associated with an increased risk of Alzheimer's disease, Parkinson's disease, and cognitive decline. Alzheimer's research & therapy Winer, J. R., Lok, R., Weed, L., He, Z., Poston, K. L., Mormino, E. C., Zeitzer, J. M. 2024; 16 (1): 35

  Abstract

  Sleep-wake regulating circuits are affected during prodromal stages in the pathological progression of both Alzheimer's disease (AD) and Parkinson's disease (PD), and this disturbance can be measured passively using wearable devices. Our objective was to determine whether accelerometer-based measures of 24-h activity are associated with subsequent development of AD, PD, and cognitive decline.This study obtained UK Biobank data from 82,829 individuals with wrist-worn accelerometer data aged 40 to 79 years with a mean (± SD) follow-up of 6.8 (± 0.9) years. Outcomes were accelerometer-derived measures of 24-h activity (derived by cosinor, nonparametric, and functional principal component methods), incident AD and PD diagnosis (obtained through hospitalization or primary care records), and prospective longitudinal cognitive testing.One hundred eighty-seven individuals progressed to AD and 265 to PD. Interdaily stability (a measure of regularity, hazard ratio [HR] per SD increase 1.25, 95% confidence interval [CI] 1.05-1.48), diurnal amplitude (HR 0.79, CI 0.65-0.96), mesor (mean activity; HR 0.77, CI 0.59-0.998), and activity during most active 10 h (HR 0.75, CI 0.61-0.94), were associated with risk of AD. Diurnal amplitude (HR 0.28, CI 0.23-0.34), mesor (HR 0.13, CI 0.10-0.16), activity during least active 5 h (HR 0.24, CI 0.08-0.69), and activity during most active 10 h (HR 0.20, CI 0.16-0.25) were associated with risk of PD. Several measures were additionally predictive of longitudinal cognitive test performance.In this community-based longitudinal study, accelerometer-derived metrics were associated with elevated risk of AD, PD, and accelerated cognitive decline. These findings suggest 24-h rhythm integrity, as measured by affordable, non-invasive wearable devices, may serve as a scalable early marker of neurodegenerative disease.

  View details for DOI 10.1186/s13195-024-01411-0

  View details for PubMedID 38355598

  View details for PubMedCentralID 4163039

• Fatigued but not sleepy? An empirical investigation of the differentiation between fatigue and sleepiness in sleep disorder patients in a cross-sectional study. Journal of psychosomatic research Suh, S., Lok, R., Weed, L., Cho, A., Mignot, E., Leary, E. B., Zeitzer, J. M. 2024; 178: 111606

  Abstract

  Sleepiness and fatigue are common complaints among individuals with sleep disorders. The two concepts are often used interchangeably, causing difficulty with differential diagnosis and treatment decisions. The current study investigated sleep disorder patients to determine which factors best differentiated sleepiness from fatigue.The study used a subset of participants from a multi-site study (n = 606), using a cross-sectional study design. We selected 60 variables associated with either sleepiness or fatigue, including demographic, mental health, and lifestyle factors, medical history, sleep questionnaires, rest-activity rhythms (actigraphy), polysomnographic (PSG) variables, and sleep diaries. Fatigue was measured with the Fatigue Severity Scale and sleepiness was measured with the Epworth Sleepiness Scale. A Random Forest machine learning approach was utilized for analysis.Participants' average age was 47.5 years (SD 14.0), 54.6% female, and the most common sleep disorder diagnosis was obstructive sleep apnea (67.4%). Sleepiness and fatigue were moderately correlated (r = 0.334). The model for fatigue (explained variance 49.5%) indicated depression was the strongest predictor (relative explained variance 42.7%), followed by insomnia severity (12.3%). The model for sleepiness (explained variance 17.9%), indicated insomnia symptoms was the strongest predictor (relative explained variance 17.6%). A post hoc receiver operating characteristic analysis indicated depression could be used to discriminate fatigue (AUC = 0.856) but not sleepiness (AUC = 0.643).The moderate correlation between fatigue and sleepiness supports previous literature that the two concepts are overlapping yet distinct. Importantly, depression played a more prominent role in characterizing fatigue than sleepiness, suggesting depression could be used to differentiate the two concepts.

  View details for DOI 10.1016/j.jpsychores.2024.111606

  View details for PubMedID 38359639

• FEELING TIRED BUT NOT SLEEPY? AN EMPIRICAL INVESTIGATION OF THE DIFFERENTIATION BETWEEN FATIGUE AND SLEEPINESS IN SLEEP DISORDER PATIENTS Suh, S., Lok, R., Weed, L., Cho, A., Mignot, E., Leary, E., Zeitzer, J. ELSEVIER. 2024: 105

  View details for Web of Science ID 001295366700275

• FULLY AUTOMATED DETECTION OF ISOLATED RAPID-EYE-MOVEMENT SLEEP BEHAVIOR DISORDER USING ACTIGRAPHY Brink-Kjaer, A., Winer, J., Zeitzer, J. M., Sorensen, H. D., Jennum, P., Mignot, E., During, E. ELSEVIER. 2024: 302

  View details for Web of Science ID 001295366702156

• Dyadic Investigation of Posttraumatic Stress Symptoms and Daily Sleep Health in Patients with Cancer and their Caregivers. Psychosomatic medicine Tsai, T. C., Mitchell, H. R., Zeitzer, J., Ting, A., Laurenceau, J. P., Spiegel, D., Kim, Y. 2024

  Abstract

  Cancer can be a traumatic experience affecting multidimensional aspects of sleep among patients and caregivers. This study examined the differential associations of cancer-related post-traumatic stress symptoms (PTSS) with various sleep markers in this population.Patients newly diagnosed with colorectal cancer (n = 138, mean age = 56.93 years, 31.88% female, 60.14% Hispanic, 6.53 months post-diagnosis) and their sleep-partner caregivers (n = 138, mean age = 55.32 years, 68.12% female, 57.97% Hispanic) completed questionnaires assessing the four PTSS clusters (intrusion, avoidance, alterations in arousal and reactivity, negative alterations in cognitions and mood). Participants also completed daily sleep diaries for 14 consecutive days, from which sleep onset latency (SOL), wake after sleep onset (WASO), and sleep duration were derived.Actor-partner interdependence model revealed that caregivers' greater alterations in arousal and reactivity were associated with their own longer SOL (b = 14.54, p < .001) and their patients' longer sleep duration (b = 0.47, p = .040), whereas patients' arousal and reactivity were associated with their caregivers' shorter SOL (b = -8.34, p = .047) and WASO (b = -8.12, p = .019). Patients' and caregivers' greater negative alterations in cognitions and mood were associated with patients' longer SOL (b = 8.89, p = .016) and shorter sleep duration (b = -0.40, p = .038), respectively. Caregivers' greater intrusion was related to their own shorter SOL (b = -10.92, p = .002).The four PTSS clusters, particularly arousal and reactivity and negative cognitions and mood, have distinct associations with sleep markers individually and dyadically in patients and caregivers affected by cancer. Investigations of psychosocial and biobehavioral pathways underlying these relations are warranted. Tailored trauma treatments and sleep interventions may improve the well-being of this population.

  View details for DOI 10.1097/PSY.0000000000001283

  View details for PubMedID 38345316

• Emotion regulation and heart rate variability may identify the optimal posttraumatic stress disorder treatment: analyses from a randomized controlled trial. Frontiers in psychiatry Mathersul, D. C., Zeitzer, J. M., Schulz-Heik, R. J., Avery, T. J., Bayley, P. J. 2024; 15: 1331569

  Abstract

  Introduction: High variability in response and retention rates for posttraumatic stress disorder (PTSD) treatment highlights the need to identify "personalized" or "precision" medicine factors that can inform optimal intervention selection before an individual commences treatment. In secondary analyses from a non-inferiority randomized controlled trial, behavioral and physiological emotion regulation were examined as non-specific predictors (that identify which individuals are more likely to respond to treatment, regardless of treatment type) and treatment moderators (that identify which treatment works best for whom) of PTSD outcome.Methods: There were 85 US Veterans with clinically significant PTSD symptoms randomized to 6 weeks of either cognitive processing therapy (CPT; n = 44) or a breathing-based yoga practice (Sudarshan kriya yoga; SKY; n = 41). Baseline self-reported emotion regulation (Difficulties in Emotion Regulation Scale) and heart rate variability (HRV) were assessed prior to treatment, and self-reported PTSD symptoms were assessed at baseline, end-of-treatment, 1-month follow-up, and 1-year follow-up.Results: Greater baseline deficit in self-reported emotional awareness (similar to alexithymia) predicted better overall PTSD improvement in both the short- and long-term, following either CPT or SKY. High self-reported levels of emotional response non-acceptance were associated with better PTSD treatment response with CPT than with SKY. However, all significant HRV indices were stronger moderators than all self-reported emotion regulation scales, both in the short- and long-term. Veterans with lower baseline HRV had better PTSD treatment response with SKY, whereas Veterans with higher or average-to-high baseline HRV had better PTSD treatment response with CPT.Conclusions: To our knowledge, this is the first study to examine both self-reported emotion regulation and HRV, within the same study, as both non-specific predictors and moderators of PTSD treatment outcome. Veterans with poorer autonomic regulation prior to treatment had better PTSD outcome with a yoga-based intervention, whereas those with better autonomic regulation did better with a trauma-focused psychological therapy. Findings show potential for the use of HRV in clinical practice to personalize PTSD treatment.Clinical trial registration: ClinicalTrials.gov identifier, NCT02366403.

  View details for DOI 10.3389/fpsyt.2024.1331569

  View details for PubMedID 38389985

• Circadian protein expression patterns in healthy young adults. Sleep health Specht, A., Kolosov, G., Cederberg, K. L., Bueno, F., Arrona-Palacios, A., Pardilla-Delgado, E., Ruiz-Herrera, N., Zitting, K. M., Kramer, A., Zeitzer, J. M., Czeisler, C. A., Duffy, J. F., Mignot, E. 2023

  Abstract

  To explore how the blood plasma proteome fluctuates across the 24-hour day and identify a subset of proteins that show endogenous circadian rhythmicity.Plasma samples from 17 healthy adults were collected hourly under controlled conditions designed to unmask endogenous circadian rhythmicity; in a subset of 8 participants, we also collected samples across a day on a typical sleep-wake schedule. A total of 6916 proteins were analyzed from each sample using the SomaScan aptamer-based multiplexed platform. We used differential rhythmicity analysis based on a cosinor model with mixed effects to identify a subset of proteins that showed circadian rhythmicity in their abundance.One thousand and sixty-three (15%) proteins exhibited significant daily rhythmicity. Of those, 431 (6.2%) proteins displayed consistent endogenous circadian rhythms on both a sleep-wake schedule and under controlled conditions: it included both known and novel proteins. When models were fitted with two harmonics, an additional 259 (3.7%) proteins exhibited significant endogenous circadian rhythmicity, indicating that some rhythmic proteins cannot be solely captured by a simple sinusoidal model. Overall, we found that the largest number of proteins had their peak levels in the late afternoon/evening, with another smaller group peaking in the early morning.This study reveals that hundreds of plasma proteins exhibit endogenous circadian rhythmicity in humans. Future analyses will likely reveal novel physiological pathways regulated by circadian clocks and pave the way for improved diagnosis and treatment for patients with circadian disorders and other pathologies. It will also advance efforts to include knowledge about time-of-day, thereby incorporating circadian medicine into personalized medicine.

  View details for DOI 10.1016/j.sleh.2023.10.005

  View details for PubMedID 38087675

• ENLIGHT: A consensus checklist for reporting laboratory-based studies on the non-visual effects of light in humans. EBioMedicine Spitschan, M., Kervezee, L., Lok, R., McGlashan, E., Najjar, R. P. 2023; 98: 104889

  Abstract

  There is no consensus on reporting light characteristics in studies investigating non-visual responses to light. This project aimed to develop a reporting checklist for laboratory-based investigations on the impact of light on non-visual physiology.A four-step modified Delphi process (three questionnaire-based feedback rounds and one face-to-face group discussion) involving international experts was conducted to reach consensus on the items to be included in the checklist. Following the consensus process, the resulting checklist was tested in a pilot phase with independent experts.An initial list of 61 items related to reporting light-based interventions was condensed to a final checklist containing 25 items, based upon consensus among experts (final n = 60). Nine items were deemed necessary to report regardless of research question or context. A description of each item is provided in the accompanying Explanation and Elaboration (E&E) document. The independent pilot testing phase led to minor textual clarifications in the checklist and E&E document.The ENLIGHT Checklist is the first consensus-based checklist for documenting and reporting ocular light-based interventions for human studies. The implementation of the checklist will enhance the impact of light-based research by ensuring comprehensive documentation, enhancing reproducibility, and enabling data aggregation across studies.Network of European Institutes for Advanced Study (NETIAS) Constructive Advanced Thinking (CAT) programme; Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust, 204686/Z/16/Z); Netherlands Organisation for Health Research and Development VENI fellowship (2020-09150161910128); U.S. Department of Defense Grant (W81XWH-16-1-0223); National University of Singapore (NUHSRO/2022/038/Startup/08); and National Research Foundation Singapore (NRF2022-THE004-0002).

  View details for DOI 10.1016/j.ebiom.2023.104889

  View details for PubMedID 38043137

• A threshold by any other name: is five minutes of wake 'long' enough to degrade sleep quality? Sleep Lok, R., Chawra, D., Zeitzer, J. M. 2023

  View details for DOI 10.1093/sleep/zsad295

  View details for PubMedID 37950748

• US Veterans Show Improvements in Subjective but Not Objective Sleep following Treatment for Posttraumatic Stress Disorder: Secondary Analyses from a Randomised Controlled Trial DEPRESSION AND ANXIETY Mathersul, D. C., Schulz-Heik, R., Avery, T. J., Allende, S., Zeitzer, J. M., Bayley, P. J. 2023; 2023

  View details for DOI 10.1155/2023/7001667

  View details for Web of Science ID 001054964900001

• Early time-restricted eating advances sleep in late sleepers: a pilot randomized controlled trial. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Blum, D. J., Hernandez, B., Zeitzer, J. M. 2023

  Abstract

  STUDY OBJECTIVES: This study evaluated the effects of early time-restricted eating (eTRE) on shifting the timing of sleep among late sleepers. Primary outcomes included actigraphy- and sleep diary-derived sleep onset, mid-sleep phase, and wake time with total sleep time as a secondary outcome.METHODS: Fifteen healthy adults with habitual late sleep timing were randomized to receive either eTRE or sleep and nutrition hygiene (control) via one, 30-minute synchronous video session. Participants completed an initial 1-week baseline phase followed by a 2-week intervention phase. Measures included continuous sleep monitoring and sleep and nutrition diaries.RESULTS: Linear-mixed effects modeling demonstrated that eTRE significantly advanced sleep timing compared to controls. Self-reported sleep onset [56.1 (20.5, 91.7) minutes], midpoint [19.5 (7.2, 31.9) minutes], and offset [42.2 (2.9, 81.5) minutes] each moved earlier in eTRE as compared to controls. Similarly, objectively determined sleep onset [66.5 (29.6, 103.4) minutes], midpoint [21.9 (9.1, 34.7) minutes], and offset [39.3 (1.3, 77.3) minutes] each moved earlier in eTRE as compared to controls. TST had a non-significant increase in the eTRE group as compared to controls.CONCLUSIONS: Late sleepers who were instructed in a single session about eTRE significantly advanced their sleep timing, especially sleep onset. eTRE shows potential as a clinical strategy for advancing sleep timing in late sleepers.CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Registry; Title: FAST Asleep: It's All About Timing; URL: https://www.chictr.org.cn/showproj.html?proj=122504; Identifier: ChiCTR2100043691.

  View details for DOI 10.5664/jcsm.10754

  View details for PubMedID 37559551

• International e-Delphi Consensus Recommendations for the Assessment and Diagnosis of Circadian rest-Activity Rhythm Disorders (CARDs) in Patients with Cancer. Cancers Gouldthorpe, C., Ancoli-Israel, S., Cash, E., Innominato, P., Jakobsen, G., Lévi, F., Miaskowski, C., Parganiha, A., Pati, A. K., Pereira, D., Revell, V., Zeitzer, J. M., Davies, A. 2023; 15 (15)

  Abstract

  Circadian rest-Activity Rhythm Disorders (CARDs) are common in patients with cancer, particularly in advanced disease. CARDs are associated with increased symptom burden, poorer quality of life, and shorter survival. Research and reporting practices lack standardization, and formal diagnostic criteria do not exist. This electronic Delphi (e-Delphi) study aimed to formulate international recommendations for the assessment and diagnosis of CARDs in patients with cancer.An international e-Delphi was performed using an online platform (Welphi). Round 1 developed statements regarding circadian rest-activity rhythms, diagnostic criteria, and assessment techniques. Rounds 2 and 3 involved participants rating their level of agreement with the statements and providing comments until consensus (defined internally as 67%) and stability between rounds were achieved. Recommendations were then created and distributed to participants for comments before being finalized.Sixteen participants from nine different clinical specialties and seven different countries, with 5-35 years of relevant research experience, were recruited, and thirteen participants completed all three rounds. Of the 164 generated statements, 66% achieved consensus, and responses were stable between the final two rounds.The e-Delphi resulted in international recommendations for assessing and diagnosing CARDs in patients with cancer. These recommendations should ensure standardized research and reporting practices in future studies.

  View details for DOI 10.3390/cancers15153784

  View details for PubMedID 37568600

• 24 h Rest/Activity Rhythms in Older Adults with Memory Impairment: Associations with Cognitive Performance and Depressive Symptomatology. Advanced biology Antonsdottir, I. M., Low, D. V., Chen, D., Rabinowitz, J. A., Yue, Y., Urbanek, J., Wu, M. N., Zeitzer, J. M., Rosenberg, P. B., Friedman, L. F., Sheikh, J. I., Yesavage, J. A., Zipunnikov, V., Spira, A. P. 2023: e2300138

  Abstract

  Little is known about links of circadian rhythm alterations with neuropsychiatric symptoms and cognition in memory impaired older adults. Associations of actigraphic rest/activity rhythms (RAR) with depressive symptoms and cognition are examined using function-on-scalar regression (FOSR). Forty-four older adults with memory impairment (mean: 76.84 ± 8.15 years; 40.9% female) completed 6.37 ± 0.93 days of actigraphy, the Beck depression inventory-II (BDI-II), mini-mental state examination (MMSE) and consortium to establish a registry for Alzheimer's disease [CERAD] delayed word recall. FOSR models with BDI-II, MMSE, or CERAD as individual predictors adjusted for demographics (Models A1-A3) and all three predictors and demographics (Model B). In Model B, higher BDI-II scores are associated with greater activity from 12:00-11:50 a.m., 2:10-5:50 p.m., 8:40-9:40 p.m., 11:20-12:00 a.m., higher CERAD scores with greater activity from 9:20-10:00 p.m., and higher MMSE scores with greater activity from 5:50-10:50 a.m. and 12:40-5:00 p.m. Greater depressive symptomatology is associated with greater activity in midafternoon, evening, and overnight into midday; better delayed recall with greater late evening activity; and higher global cognitive performance with greater morning and afternoon activity (Model B). Time-of-day specific RAR alterations may affect mood and cognitive performance in this population.

  View details for DOI 10.1002/adbi.202300138

  View details for PubMedID 37423973

• Heart rate variability is a moderator of treatment outcome for posttraumatic stress disorder: Secondary analyses from a randomised controlled trial Mathersul, D., Schulz-Heik, J., Avery, T., Zeitzer, J., Bayley, P. ELSEVIER. 2023: 80

  View details for DOI 10.1016/j.ijpsycho.2023.05.208

  View details for Web of Science ID 001037996300207

• Improvements in Immediate and Delayed Memory With Insomnia Therapy and Their Associations With SWA in Older Adults Ahmadi, M., Krause, A. J., O'Hora, K. P., Hernandez, B., Lazzeroni, L., Zeitzer, J. M., Friedman, L. F., Posner, D., Kushida, C. A., Yesavage, J. A., Saletin, J., Goldstein-Piekarski, A. ELSEVIER SCIENCE INC. 2023: S301

  View details for Web of Science ID 000993018500730

• ASSOCIATIONS OF SELF-DISCLOSURE WITH SLEEP IN CANCER PATIENTS AND THEIR SLEEP-PARTNER CAREGIVERS: A DYADIC INVESTIGATION Tsai, T. C., Ajmera, N., Ting, A., Laurenceau, J., Zeitzer, J., Kim, Y. LIPPINCOTT WILLIAMS & WILKINS. 2023: A105

  View details for Web of Science ID 001167041400259

• PHASE SHIFTING IN RESPONSE TO LIGHT FLASH SEQUENCES DURING SLEEP Lok, R., Zeitzer, J. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001008232900315

• PERILS OF THE NIGHTTIME: IMPACT OF BEHAVIORAL TIMING AND PREFERENCE ON MENTAL AND PHYSICAL HEALTH Zeitzer, J., Lok, R., Weed, L., Winer, J. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001008232900019

• ADULTS WITH AND WITHOUT MILD COGNITIVE IMPAIRMENT SHOW SIMILAR TREATMENT ADHERENCE AND SLEEP IMPROVEMENT AFTER INSOMNIA THERAPY Morehouse, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2023

  View details for Web of Science ID 001008232900380

• Brief structured respiration practices enhance mood and reduce physiological arousal. Cell reports. Medicine Balban, M. Y., Neri, E., Kogon, M. M., Weed, L., Nouriani, B., Jo, B., Holl, G., Zeitzer, J. M., Spiegel, D., Huberman, A. D. 2023: 100895

  Abstract

  Controlled breathwork practices have emerged as potential tools for stress management and well-being. Here, we report a remote, randomized, controlled study (NCT05304000) of three different daily 5-min breathwork exercises compared with an equivalent period of mindfulness meditation over 1 month. The breathing conditions are (1) cyclic sighing, which emphasizes prolonged exhalations; (2) box breathing, which is equal duration of inhalations, breath retentions, and exhalations; and (3) cyclic hyperventilation with retention, with longer inhalations and shorter exhalations. The primary endpoints are improvement in mood and anxiety as well as reduced physiological arousal (respiratory rate, heart rate, and heart rate variability). Using a mixed-effects model, we show that breathwork, especially the exhale-focused cyclic sighing, produces greater improvement in mood (p < 0.05) and reduction in respiratory rate (p < 0.05) compared with mindfulness meditation. Daily 5-min cyclic sighing has promise as an effective stress management exercise.

  View details for DOI 10.1016/j.xcrm.2022.100895

  View details for PubMedID 36630953

• Fully Automated Detection of Isolated Rapid-Eye-Movement Sleep Behavior Disorder Using Actigraphy. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Brink-Kjaer, A., Winer, J., Zeitzer, J. M., Sorensen, H. B., Jennum, P., Mignot, E., During, E. 2023; 2023: 1-5

  Abstract

  Isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD) is caused by motor disinhibition during REM sleep and is a strong early predictor of Parkinson's disease. However, screening questionnaires for iRBD lack specificity due to other sleep disorders that mimic the symptoms. Nocturnal wrist actigraphy has shown promise in detecting iRBD by measuring sleep-related motor activity, but it relies on sleep diary-defined sleep periods, which are not always available. Our aim was to precisely detect iRBD using actigraphy alone by combining two actigraphy-based markers of iRBD - abnormal nighttime activity and 24-hour rhythm disruption. In a sample of 42 iRBD patients and 42 controls (21 clinical controls with other sleep disorders and 21 community controls) from the Stanford Sleep Clinic, the nighttime actigraphy model was optimized using automated detection of sleep periods. Using a subset of 38 iRBD patients with daytime data and 110 age-, sex-, and body-mass-index-matched controls from the UK Biobank, the 24-hour rhythm actigraphy model was optimized. Both nighttime and 24-hour rhythm features were found to distinguish iRBD from controls. To improve the accuracy of iRBD detection, we fused the nighttime and 24-hour rhythm disruption classifiers using logistic regression, which achieved a sensitivity of 78.9%, a specificity of 96.4%, and an AUC of 0.954. This study preliminarily validates a fully automated method for detecting iRBD using actigraphy in a general population.Clinical relevance- Actigraphy-based iRBD detection has potential for large-scale screening of iRBD in the general population.

  View details for DOI 10.1109/EMBC40787.2023.10341133

  View details for PubMedID 38083699

• A Flexible Deep Learning Architecture for Temporal Sleep Stage Classification Using Accelerometry and Photoplethysmography IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Olsen, M., Zeitzer, J. M., Richardson, R. N., Davidenko, P., Jennum, P. J., Sorensen, H. D., Mignot, E. 2023; 70 (1): 228-237

  Abstract

  Wrist-worn consumer sleep technologies (CST) that contain accelerometers (ACC) and photoplethysmography (PPG) are increasingly common and hold great potential to function as out-of-clinic (OOC) sleep monitoring systems. However, very few validation studies exist because raw data from CSTs are rarely made accessible for external use. We present a deep neural network (DNN) with a strong temporal core, inspired by U-Net, that can process multivariate time series inputs with different dimensionality to predict sleep stages (wake, light-, deep-, and REM sleep) using ACC and PPG signals from nocturnal recordings. The DNN was trained and tested on 3 internal datasets, comprising raw data both from clinical and wrist-worn devices from 301 recordings (PSG-PPG: 266, Wrist-worn PPG: 35). External validation was performed on a hold-out test dataset containing 35 recordings comprising only raw data from a wrist-worn CST. An accuracy = 0.71±0.09, 0.76±0.07, 0.73±0.06, and κ = 0.58±0.13, 0.64±0.09, 0.59±0.09 was achieved on the internal test sets. Our experiments show that spectral preprocessing yields superior performance when compared to surrogate-, feature-, raw data-based preparation. Combining both modalities produce the overall best performance, although PPG proved to be the most impactful and was the only modality capable of detecting REM sleep well. Including ACC improved model precision to wake and sleep metric estimation. Increasing input segment size improved performance consistently; the best performance was achieved using 1024 epochs (∼8.5 hrs.). An accuracy = 0.69±0.13 and κ = 0.58±0.18 was achieved on the hold-out test dataset, proving the generalizability and robustness of our approach to raw data collected with a wrist-worn CST.

  View details for DOI 10.1109/TBME.2022.3187945

  View details for Web of Science ID 000936179400023

  View details for PubMedID 35786544

• Optimizing Light Flash Sequence Duration to Shift Human Circadian Phase. Biology Joyce, D. S., Spitschan, M., Zeitzer, J. M. 2022; 11 (12)

  Abstract

  Unlike light input for forming images, non-image-forming retinal pathways are optimized to convey information about the total light environment, integrating this information over time and space. In a variety of species, discontinuous light sequences (flashes) can be effective stimuli, notably impacting circadian entrainment. In this study, we examined the extent to which this temporal integration can occur. A group of healthy, young (n = 20) individuals took part in a series of 16-day protocols in which we examined the impact of different lengths of light flash sequences on circadian timing. We find a significant phase change of -0.70 h in response to flashes that did not differ by duration; a 15-min sequence could engender as much change in circadian timing as 3.5-h sequences. Acute suppression of melatonin was also observed during short (15-min) exposures, but not in exposures over one hour in length. Our data are consistent with the theory that responses to light flashes are mediated by the extrinsic, rod/cone pathway, and saturate the response of this pathway within 15 min. Further excitation leads to no greater change in circadian timing and an inability to acutely suppress melatonin, indicating that this pathway may be in a refractory state following this brief light stimulation.

  View details for DOI 10.3390/biology11121807

  View details for PubMedID 36552316

• PASSIVE PHOTOTHERAPY INCREASES SLEEP DURATION IN TEENS Zeitzer, J. M. ELSEVIER SCIENCE INC. 2022: S302

  View details for DOI 10.1016/j.jaac.2022.07.652

  View details for Web of Science ID 000873567901346

• The Impact of Missing Data and Imputation Methods on the Analysis of 24-Hour Activity Patterns. Clocks & sleep Weed, L., Lok, R., Chawra, D., Zeitzer, J. 2022; 4 (4): 497-507

  Abstract

  The purpose of this study is to characterize the impact of the timing and duration of missing actigraphy data on interdaily stability (IS) and intradaily variability (IV) calculation. The performance of three missing data imputation methods (linear interpolation, mean time of day (ToD), and median ToD imputation) for estimating IV and IS was also tested. Week-long actigraphy records with no non-wear or missing timeseries data were masked with zeros or 'Not a Number' (NaN) across a range of timings and durations for single and multiple missing data bouts. IV and IS were calculated for true, masked, and imputed (i.e., linear interpolation, mean ToD and, median ToD imputation) timeseries data and used to generate Bland-Alman plots for each condition. Heatmaps were used to analyze the impact of timings and durations of and between bouts. Simulated missing data produced deviations in IV and IS for longer durations, midday crossings, and during similar timing on consecutive days. Median ToD imputation produced the least deviation among the imputation methods. Median ToD imputation is recommended to recapitulate IV and IS under missing data conditions for less than 24 h.

  View details for DOI 10.3390/clockssleep4040039

  View details for PubMedID 36278532

• Associations of 24-hour Light Exposure and Activity Patterns and Risk of Cognitive Impairment and Decline in Older Men: The MrOS Sleep Study. The journals of gerontology. Series A, Biological sciences and medical sciences Blackwell, T. L., Figueiro, M. G., Tranah, G. J., Zeitzer, J. M., Yaffe, K., Ancoli-Israel, S., Kado, D. M., Ensrud, K. E., Lane, N. E., Leng, Y., Stone, K. L., Osteoporotic Fractures in Men (MrOS) Study Group 2022

  Abstract

  BACKGROUND: Older men with worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline.METHODS: This cohort consisted of 1,036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009-2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify alignment of light-dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination, 3MS) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education and season.RESULTS: Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (Quartile 1 vs. Quartile 4, p=.02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation increase in phasor magnitude (95% CI 0.7-10.4, p=.03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS).CONCLUSIONS: Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve alignment of light and activity may slow cognitive decline in older adults.

  View details for DOI 10.1093/gerona/glac187

  View details for PubMedID 36156079

• Randomised clinical non-inferiority trial of breathing-based meditation and cognitive processing therapy for symptoms of post-traumatic stress disorder in military veterans. BMJ open Bayley, P. J., Schulz-Heik, R. J., Tang, J. S., Mathersul, D. C., Avery, T., Wong, M., Zeitzer, J. M., Rosen, C. S., Burn, A. S., Hernandez, B., Lazzeroni, L. C., Seppala, E. M. 2022; 12 (8): e056609

  Abstract

  OBJECTIVE: Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial.SETTING: Outpatient Veterans Affairs healthcare centre.PARTICIPANTS: 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study.INTERVENTIONS: SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks.MEASURES: The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS).RESULTS: Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6weeks (end of treatment) relative to baseline (SKY, -5.6, d=0.41, n=41: CPT, -6.8, d=0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (-1.2, 95%CI -5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT-SKY: -2.1, 95%CI -6.9 to 2.8) and 1-year (CPT-SKY: -1.8, 95%CI -6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1month, but SKY was inferior to CPT on both BDI-II and PANAS at 1year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95%CI 0.51 to 3.62, p=0.54).CONCLUSIONS: SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD.TRIAL REGISTRATION NUMBER: NCT02366403.

  View details for DOI 10.1136/bmjopen-2021-056609

  View details for PubMedID 36008059

• THE IMPACT OF NON-PHARMACOLOGICAL INSOMNIA THERAPY ON MOOD AND SLEEP IN MORNING AND EVENING CHRONOTYPES IN OLDER ADULTS Lopez, M., Krause, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A211-A212

  View details for Web of Science ID 000838094800474

• SLEEP-WAKE STABILITY AND VARIABILITY IN THE MIDDLE-AGED ADULT POPULATION: A UK BIOBANK STUDY Lok, R., Weed, L., Chawra, D., Winer, J., Zeitzer, J. OXFORD UNIV PRESS INC. 2022: A73-A74

  View details for Web of Science ID 000838094800159

• N2 AND WAKEFULNESS DRIVE SUBJECTIVE SLEEP SATISFACTION IN ADULTS Lok, R., Chawra, D., Hon, F., Ha, M., Kaplan, K., Zeitzer, J. OXFORD UNIV PRESS INC. 2022: A99

  View details for Web of Science ID 000838094800218

• ISOLATED REM SLEEP BEHAVIOR DISORDER IS ASSOCIATED WITH 24-HOUR RHYTHM DISRUPTION Winer, J., Lok, R., Cahuas, A., Bueno, F., Poston, K., Mormino, E., Zeitzer, J., During, E. OXFORD UNIV PRESS INC. 2022: A125

  View details for Web of Science ID 000838094800278

• DYADIC INVESTIGATIONS OF ADULT ATTACHMENT AND SLEEP IN ADULT CANCER PATIENTS AND THEIR CAREGIVERS Ting, A., Zeitzer, J., Wohlgemuth, W., Tsai, T. C., Ajmera, N., Kim, Y. LIPPINCOTT WILLIAMS & WILKINS. 2022: A67

  View details for Web of Science ID 000804854700203

• REST-ACTIVITY PROFILES AMONG US ADULTS IN A NATIONALLY REPRESENTATIVE SAMPLE: A FUNCTIONAL PRINCIPAL COMPONENT ANALYSIS Xiao, Q., Lu, J., Matthews, C., Zeitzer, J., Saint-Maurice, P., Bauer, C. OXFORD UNIV PRESS INC. 2022: A72

  View details for Web of Science ID 000838094800156

• NON-PHARMACOLOGICAL INSOMNIA THERAPY IS ROBUST TO CO-OCCURRING PAIN IN OLDER ADULTS Krause, A., Ahmadi, M., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Saletin, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A197-A198

  View details for Web of Science ID 000838094800441

• EFFECT OF SELF-REGULATION ON SLEEP IN COLORECTAL CANCER PATIENTS: THE MEDIATING ROLE OF NEGATIVE AFFECT RECOVERY Tsai, T. C., Ting, A., Llabre, M., Martinez, L., Zeitzer, J., Kim, Y. LIPPINCOTT WILLIAMS & WILKINS. 2022: A82

  View details for Web of Science ID 000804854700247

• THE EFFECT OF DISTINCT COMPONENTS OF CBT-I ON SLOW WAVE POWER AND ENERGY Ahmadi, M., Krause, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Saletin, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A197

  View details for Web of Science ID 000838094800440

• THE EFFECTS OF INSOMNIA THERAPY ON DEPRESSION, ANXIETY, AND DAILY FUNCTIONING IN INDIVIDUALS WITH INSOMNIA AND MILD COGNITIVE IMPAIRMENT Morehouse, A., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2022: A275-A276

  View details for Web of Science ID 000838094800623

• Circadian photoreception: The impact of light on human circadian rhythms. Progress in brain research Zeitzer, J. M., Lok, R. 2022; 273 (1): 171-180

  Abstract

  Light is the preeminent external influence in determining the position of the internal circadian clock relative to the outside world. In this chapter, we discuss the different parameters of light that impact how it influences the human circadian clock. We detail how the timing (phase), intensity, duration and temporal structure, and spectral composition all can modulate the impact of light on both the timing of the circadian clock as well as its amplitude. The neurobiological underpinnings of the system are briefly discussed in the context of understanding how light can evoke its observed effects on the circadian clock.

  View details for DOI 10.1016/bs.pbr.2022.04.005

  View details for PubMedID 35940715

• Non-Pharmacological Insomnia Therapy is Robust to Co-Occurring Pain in Older Adults Krause, A., Ahmadi, M., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Saletin, J., Goldstein-Piekarski, A. ELSEVIER SCIENCE INC. 2022: S370

  View details for Web of Science ID 000789022201277

• Circadian Sub-Groups in Bipolar I Disorder Gonzalez, R., Dwivedi, A., Zeitzer, J., Suppes, T., Tohen, M., Forero, A., Alvarado, L. ELSEVIER SCIENCE INC. 2022: S153-S154

  View details for Web of Science ID 000789022200377

• The Effect of Distinct Components of CBT-I on Slow Wave Power and Energy Ahmadi, M., Krause, A. J., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J. A., Saletin, J., Goldstein-Piekarski, A. ELSEVIER SCIENCE INC. 2022: S369-S370

  View details for Web of Science ID 000789022201276

• Emotion dysregulation and heart rate variability improve in US veterans undergoing treatment for posttraumatic stress disorder: Secondary exploratory analyses from a randomised controlled trial. BMC psychiatry Mathersul, D. C., Dixit, K., Schulz-Heik, R. J., Avery, T. J., Zeitzer, J. M., Bayley, P. J. 2022; 22 (1): 268

  Abstract

  BACKGROUND: Emotion regulation (ER) is a key process underlying posttraumatic stress disorder (PTSD), yet, little is known about how ER changes with PTSD treatment. Understanding these effects may shed light on treatment processes.METHODS: We recently completed a non-inferiority design randomised controlled trial demonstrating that a breathing-based yoga practice (Sudarshan kriya yoga; SKY) was not clinically inferior to cognitive processing therapy (CPT) across symptoms of PTSD, depression, or negative affect. Here, in secondary exploratory analyses (intent-to-treat N=85; per protocol N=59), we examined whether self-reported ER (Difficulties in Emotion Regulation Scale; DERS) and physiological ER (heart rate variability; HRV) improved with treatment for clinically significant PTSD symptoms among US Veterans.RESULTS: DERS-Total and all six subscales improved with small-to-moderate effect sizes (d=.24-.66) following CPT or SKY, with no differences between treatment groups. Following SKY (but not CPT), HR max-min (average difference between maximum and minimum beats per minute), LF/HF (low-to-high frequency) ratio, and normalised HF-HRV (high frequency power) improved (moved towards a healthier profile; d=.42-.55).CONCLUSIONS: To our knowledge, this is the first study to demonstrate that a breathing-based yoga (SKY) improved both voluntary/intentional and automatic/physiological ER. In contrast, trauma-focused therapy (CPT) only reliably improved self-reported ER. Findings have implications for PTSD treatment and interventions for emotional disorders more broadly.TRIAL REGISTRATION: Secondary analyses of ClinicalTrials.gov NCT02366403 .

  View details for DOI 10.1186/s12888-022-03886-3

  View details for PubMedID 35428258

• Rest-activity profiles among U.S. adults in a nationally representative sample: a functional principal component analysis. The international journal of behavioral nutrition and physical activity Xiao, Q., Lu, J., Zeitzer, J. M., Matthews, C. E., Saint-Maurice, P. F., Bauer, C. 2022; 19 (1): 32

  Abstract

  BACKGROUND: The 24-h rest and activity behaviors (i.e., physical activity, sedentary behaviors and sleep) are fundamental human behaviors essential to health and well-being. Functional principal component analysis (fPCA) is a flexible approach for characterizing rest-activity rhythms and does not rely on a priori assumptions about the activity shape. The objective of our study is to apply fPCA to a nationally representative sample of American adults to characterize variations in the 24-h rest-activity pattern, determine how the pattern differs according to demographic, socioeconomic and work characteristics, and examine its associations with general health status.METHODS: The current analysis used data from adults 25 or older in the National Health and Nutrition Examination Survey (NHANES, 2011-2014). Using 7-day 24-h actigraphy recordings, we applied fPCA to derive profiles for overall, weekday and weekend rest-activity patterns. We examined the association between each rest-activity profile in relation to age, gender, race/ethnicity, education, income and working status using multiple linear regression. We also used multiple logistic regression to determine the relationship between each rest-activity profile and the likelihood of reporting poor or fair health.RESULTS: We identified four distinct profiles (i.e., high amplitude, early rise, prolonged activity window, biphasic pattern) that together accounted for 86.8% of total variation in the study sample. We identified numerous associations between each rest-activity profile and multiple sociodemographic characteristics. We also found evidence suggesting the associations differed between weekdays and weekends. Finally, we reported that the rest-activity profiles were associated with self-rated health.CONCLUSIONS: Our study provided evidence suggesting that rest-activity patterns in human populations are shaped by multiple demographic, socioeconomic and work factors, and are correlated with health status.

  View details for DOI 10.1186/s12966-022-01274-4

  View details for PubMedID 35331274

• Duration invariance and intensity dependence of the human circadian system phase shifting response to brief light flashes. Proceedings. Biological sciences Joyce, D. S., Spitschan, M., Zeitzer, J. M. 2022; 289 (1970): 20211943

  Abstract

  The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterized by a delayed off-time following the cessation of light stimulation. Here, we exploited this unusual physiologic property to characterize the exquisite sensitivity of the human circadian system to flashed light. In a 34 h in-laboratory between-subjects design, we examined phase shifting in response to variable-intensity (3-9500 photopic lux) flashes at fixed duration (2 ms; n = 28 participants) and variable-duration (10 s-10 s) flashes at fixed intensity (2000 photopic lux; n = 31 participants). Acute melatonin suppression, objective alertness and subjective sleepiness during the flash sequence were also assessed. We find a dose-response relationship between flash intensity and circadian phase shift, with an indication of a possible threshold-like behaviour. We find a slight parametric relationship between flash duration and circadian phase shift. Consistent with prior studies, we observe no dose-response relationship to either flash intensity or duration and the acute impact of light on melatonin suppression, objective alertness or subjective sleepiness. Our findings are consistent with circadian responses to a sequence of flashes being mediated by rod or cone photoreceptors via ipRGC integration.

  View details for DOI 10.1098/rspb.2021.1943

  View details for PubMedID 35259981

• Investigation of the aging clock's intermittent-light responses uncovers selective deficits to green millisecond flashes. Journal of photochemistry and photobiology. B, Biology Kaladchibachi, S., Negelspach, D. C., Zeitzer, J. M., Fernandez, F. 1800; 228: 112389

  Abstract

  The central pacemaker of flies, rodents, and humans generates less robust circadian output signals across normative aging. It is not well understood how changes in light sensitivity might contribute to this phenomenon. In the present study, we summarize results from an extended data series (n=5681) showing that the locomotor activity rhythm of aged Drosophila can phase-shift normally to intermittently spaced episodes of bright polychromatic light exposure (600lx) but that deficits emerge in response to 8, 16, and 120-millisecond flashes of narrowband blue (lambdam, 452nm) and green (lambdam, 525nm) LED light. For blue, phase-resetting of the activity rhythm of older flies is not as energy efficient as it is in younger flies at the fastest flash-exposures tested (8 milliseconds), suggesting there might be different floors of light duration necessary to incur photohabituation in each age group. For green, the responses of older flies are universally crippled relative to those of younger flies across the slate of protocols we tested. The difference in green flash photosensitivity is one of the most salient age-related phenotypes that has been documented in the circadian phase-shifting literature thus far. These data provide further impetus for investigations on pacemaker aging and how it might relate to changes in the circadian system's responses to particular sequences of light exposure tuned for wavelength, intensity, duration, and tempo.

  View details for DOI 10.1016/j.jphotobiol.2022.112389

  View details for PubMedID 35086027

• Methodological Considerations for the Experimental Control of Photoreception in Humans MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 14-18

  View details for Web of Science ID 000951076000004

• Circadian Rhythms and ipRGCs MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 28-32

  View details for Web of Science ID 000951076000009

• Introduction MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 1-+

  View details for Web of Science ID 000951076000001

• Melanopsin-Driven Light Adaptation Modulates Rod- and Cone-Mediated Functions MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 21-23

  View details for Web of Science ID 000951076000006

• Future Directions, Unknowns, and Conclusions MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 39-41

  View details for Web of Science ID 000951076000012

• Melanopsin-Expressing ipRGCs Drive an Independent Dimension of Conscious Visual Perception in Humans MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 25-28

  View details for Web of Science ID 000951076000008

• The Non-image-Forming Pathways Set Arousal and Cognition MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 32-36

  View details for Web of Science ID 000951076000010

• Spatio-Temporal Response Properties of Melanopsin Photoreception MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 23-25

  View details for Web of Science ID 000951076000007

• Intrinsically Photosensitive Retinal Ganglion Cells MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 4-14

  View details for Web of Science ID 000951076000003

• The Pupil as a Measure of Non-image-Forming Vision MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 18-21

  View details for Web of Science ID 000951076000005

• Harnessing Light in the Built Environment MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 36-39

  View details for Web of Science ID 000951076000011

• Evidence for the Non-image-Forming Pathways and Novel Retinal Photoreceptors MELANOPSIN VISION Joyce, D. S., Houser, K. W., Peirson, S. N., Zeitzer, J. M., Zele, A. J., Joyce, D., Houser, K., Peirson, S., Zeitzer, J., Zele, A. 2022: 2-4

  View details for Web of Science ID 000951076000002

• Chronbiologically-based sub-groups in bipolar I disorder: A latent profile analysis. Journal of affective disorders Gonzalez, R., Dwivedi, A., Zeitzer, J., Suppes, T., Tohen, M., Forero, A., Alvarado, A. 2021

  Abstract

  BACKGROUND: Bipolar disorder presents with significant phenotypic heterogeneity. The aim of this study was to investigate whether bipolar disorder, type I (BDI) subjects could be meaningfully classified into homogeneous groups according to activity, sleep, and circadian characteristics using latent profile analysis (LPA). We hypothesized that distinct BDI sub-groups would be identified based primarily on circadian-associated markers.MATERIALS AND METHODS: 105 individuals with BDI were included in the study. Seventeen activity, sleep, and circadian characteristics were assessed via actigraphy and clinical assessments. LPA was conducted to stratify our sample into homogenous sub-groups. Differences between groups on demographic, clinical, activity, sleep, and circadian characteristics were explored.RESULTS: Two distinct groups were identified, a High Chronobiological Disturbance group (HCD) (56%, N = 59) and a Low Chronobiological Disturbance group (LCD) (41%; N = 46). Circadian variables were the defining characteristics in sub-group determination. Large effect sizes and magnitudes of association were noted in circadian variables between HCD and LCD sub-groups. Several circadian rhythm variables accounted for a large percentage of the variance between HCD and LCD sub-groups. No differences were noted between sub-groups on demographic characteristics and the psychiatric medications currently in use. Mood state did not significantly impact sub-group differences.LIMITATIONS: The protocol was cross-sectional in design. Longitudinal studies are required to determine the stability of the identified sub-groups.CONCLUSION: LPA was able to identify sub-groups in BDI with circadian variables being the most distinguishing factors in determining sub-group class membership. Future research should explore the role that circadian characteristics can play in defining sub-phenotypes of bipolar disorder.

  View details for DOI 10.1016/j.jad.2021.12.010

  View details for PubMedID 34879259

• Self-reported and actigraphic short sleep duration in older adults. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Miner, B., Stone, K. L., Zeitzer, J. M., Han, L., Doyle, M., Blackwell, T., Gill, T. M., Redeker, N. S., Hajduk, A., Yaggi, H. K. 2021

  Abstract

  STUDY OBJECTIVES: Persons > 65 years with short sleep duration (≤ 6 hours) are at risk for adverse outcomes, but the accuracy of self-reported sleep duration may be affected by reduced symptom awareness. We evaluated the performance characteristics of self-reported versus objectively-measured sleep duration in this age group.METHODS: In 2,980 men from the Osteoporotic Fractures in Men Sleep Study (MrOS) and 2,855 women from the Study of Osteoporotic Fractures (SOF), we examined the agreement and accuracy of self-reported versus actigraphy-measured short and normal (> 6 but < 9 hours) sleep duration. We evaluated associations of select factors (demographics, medical, physical, and neuropsychiatric conditions, medication and substance use, and sleep-related measures) with risk of false-negative (normal sleep duration by self-report but short sleep duration by actigraphy) and false-positive (short sleep duration by self-report and normal sleep duration by actigraphy) designations, respectively, using logistic regression.RESULTS: Average ages were 76.3 ± 5.5 and 83.5 ± 3.7 years in men and women, respectively. There was poor agreement between self-reported and actigraphic sleep duration (Kappa ≤ 0.24). False-negatives occurred in nearly half and false-positives in over a quarter of older persons. In multivariable models in men and women, false-negatives were independently associated with obesity, daytime sleepiness, and napping, while false-positives were significantly lower with obesity.CONCLUSIONS: Under- and over-reporting of short sleep is common among older persons. Reliance on self-report may lead to missed opportunities to prevent adverse outcomes or unnecessary interventions. Self-reported sleep duration should be objectively confirmed when evaluating the effect of sleep duration on health outcomes.

  View details for DOI 10.5664/jcsm.9584

  View details for PubMedID 34338629

• Heart rate and heart rate variability as outcomes and longitudinal moderators of treatment for pain across follow-up in Veterans with Gulf War illness. Life sciences Mathersul, D. C., Dixit, K., Avery, T. J., Schulz-Heik, R. J., Zeitzer, J. M., Mahoney, L. A., Cho, R. H., Bayley, P. J. 2021: 119604

  Abstract

  AIMS: Accumulating evidence suggests Gulf War illness (GWI) is characterised by autonomic nervous system dysfunction (higher heart rate [HR], lower heart rate variability [HRV]). Yoga - an ancient mind-body practice combining mindfulness, breathwork, and physical postures - is proposed to improve autonomic dysfunction yet this remains untested in GWI. We aimed to determine (i) whether HR and HRV improve among Veterans with GWI receiving either yoga or cognitive behavioural therapy (CBT) for pain; and (ii) whether baseline autonomic functioning predicts treatment-related pain outcomes across follow-up.MAIN METHODS: We present secondary analyses of 24-hour ambulatory cardiac data (mean HR, square root of the mean squared differences between successive R-R intervals [RMSSD], high frequency power [HF-HFV], and low-to-high frequency ratio [LF/HF] extracted from a 5-min window during the first hour of sleep) from our randomised controlled trial of yoga versus CBT for pain among Veterans with GWI (ClinicalTrials.govNCT02378025; N = 75).KEY FINDINGS: Veterans who received CBT tended towards higher mean HR at end-of-treatment. Better autonomic function (lower mean HR, higher RMSSD/HF-HRV) at baseline predicted greater reductions in pain across follow-up, regardless of treatment group. Better baseline autonomic function (mid-range-to-high RMSSD/HF-HRV) also predicted greater pain reductions with yoga, while worse baseline autonomic function (higher mean HR, lower RMSSD/HF-HRV) predicted greater pain reductions with CBT.SIGNIFICANCE: To our knowledge, this is the first study to suggest that among Veterans with GWI, HR may increase with CBT yet remain stable with yoga. Furthermore, HR and HRV moderated pain outcome across follow-up for yoga and CBT.

  View details for DOI 10.1016/j.lfs.2021.119604

  View details for PubMedID 33984356

• RELATIVE EFFECTIVENESS OF COGNITIVE BEHAVIORAL THERAPY AND ITS COMPONENTS IN IMPROVING INSOMNIA SYMPTOMS IN OLDER ADULTS O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2021: A144

  View details for Web of Science ID 000698984300360

• PHYSIOLOGICAL CORRELATES OF THE EPWORTH SLEEPINESS SCALE REVEAL DIFFERENT DIMENSIONS OF DAYTIME SLEEPINESS. Lok, R., Zeitzer, J. OXFORD UNIV PRESS INC. 2021: A45

  View details for Web of Science ID 000698984300109

• EFFICACY OF CBT-I AND ITS COMPONENTS ON HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN OLDER ADULTS Showen, K., O'Hora, K., Hernandez, B., Lazzeroni, L., Zeitzer, J., Friedman, L., Posner, D., Kushida, C., Yesavage, J., Goldstein-Piekarski, A. OXFORD UNIV PRESS INC. 2021: A143-A144

  View details for Web of Science ID 000698984300359

• Social dominance and multiple dimensions of psychopathology: An experimental test of reactivity to leadership and subordinate roles. PloS one Johnson, S. L., Swerdlow, B. n., Tharp, J. A., Chen, S. n., Tackett, J. n., Zeitzer, J. n. 2021; 16 (4): e0250099

  Abstract

  Theory and research suggest that social dominance is important for multiple forms of psychopathology, and yet few studies have considered multiple dimensions of psychopathology simultaneously, and relatively few have used well-validated behavioral indices.Among 81 undergraduates, we used a well-validated experimental approach of assigning participants to a leadership or subordinate position, and we examined how self-rated severity of depression, social anxiety, manic tendencies, and psychopathy relate to psychophysiological and affective reactivity to this role.Consistent with hypotheses, manic symptoms related to more discomfort in the subordinate role compared to the leadership role, as evidenced by more decline in positive affect, more discomfort, and a larger RSA decline, while depression symptoms related to a more positive response to the subordinate role than the leadership role, including more positive affect and more comfort in the assigned role. Social anxiety was related to discomfort regardless of the assigned role, and those with higher psychopathy symptoms did not show differential response to assigned roles.Findings are limited by the mild symptom levels and absence of hormonal data.Findings provide novel transdiagnostic evidence for the importance of social dominance to differentiate diverse forms of psychopathology.

  View details for DOI 10.1371/journal.pone.0250099

  View details for PubMedID 33909641

• Translation and Validation of a Chinese Version of the Cleveland Adolescent Sleepiness Questionnaire. Nature and science of sleep Yang, Y., Chang, H., Hsu, C., Zeitzer, J. M. 2021; 13: 695-702

  Abstract

  Purpose: The Cleveland Adolescent Sleepiness Questionnaire was originally developed and published in English and has served as a valid and effective tool for the assessment of adolescents' experiences with sleepiness in a variety of situations. To allow for comparisons between sleepiness in adolescents from different cultures, and with different linguistic backgrounds, reliable and valid measurement tools are necessary. The purpose of this study was to translate and validate a Chinese version of the Cleveland Adolescent Sleepiness Questionnaire (C-CASQ).Materials and Methods: Sensitivity, specificity, internal consistency, and criterion validity data for the C-CASQ were tested using 458 adolescents in Taiwan. Data from 191 participants were used to establish internal consistency reliability and conduct exploratory factor analysis (EFA), while data from 267 participants were used to establish criterion validity and conduct confirmatory factor analysis (CFA). Initial criterion validity was established through a comparison of the C-CASQ with scores from the Chinese version of the Morningness-Eveningness Scale for Children, a measure of chronotype.Results: EFA resulted in four factors, consistent with the original English version of the CASQ, while CFA established goodness of fit. The scale demonstrated acceptable to good internal consistency (alpha = 0.77~0.86). Initial criterion validity was evident as the total score and each of the subscale scores on the C-CASQ was significantly higher (greater sleepiness) in evening-types.Conclusion: The C-CASQ appears to be a psychometrically sound measure to evaluate sleepiness in Chinese-speaking adolescents.

  View details for DOI 10.2147/NSS.S262572

  View details for PubMedID 34104022

• REST-ACTIVITY RHYTHM PATTERNS AND PHYSICAL FUNCTIONAL PERFORMANCE IN COMMUNITY-DWELLING OLDER MEN Chen, D., Tranah, G., Bradshaw, P., Blackwell-Hoge, T., Zeitzer, J., Ancoli-Israel, S., Yaffe, K., Stone, K. OXFORD UNIV PRESS. 2021: 336-337

  View details for Web of Science ID 000842009901559

• Physiological correlates of the Epworth Sleepiness Scale reveal different dimensions of daytime sleepiness. Sleep advances : a journal of the Sleep Research Society Lok, R., Zeitzer, J. M. 2021; 2 (1): zpab008

  Abstract

  The Epworth Sleepiness Scale is commonly used to examine self-reported daytime sleepiness in clinical populations; the physiologic correlates of this scale, however, are not well understood. Furthermore, how well this scale correlates with parallel objective and self-reported concepts of daytime sleepiness is not well described. As such, we used machine learning algorithms to examine the association between Epworth Sleepiness Scale scores and 55 sleep and medical variables in the Sleep Heart Health Study (N = 2105). Secondary analyses examined data stratified by age and gender and the relationship between the Epworth and other measures of daytime sleepiness. Analyses of the main data set resulted in low explained variance (7.15%-10.0%), with self-reported frequency of not getting enough sleep as most important predictor (10.3%-13.9% of the model variance). Stratification by neither age nor gender significantly improved explained variance. Cross-correlational analysis revealed low correlation of other daytime sleepiness measures to Epworth scores. We find that Epworth scores are not well explained by habitual or polysomnographic sleep values, or other biomedical characteristics. These analyses indicate that there are different, potentially orthogonal dimensions of the concept of "daytime sleepiness" that may be driven by different aspects of sleep physiology. As the physiologic correlates of the Epworth Sleepiness Scale remain to be elucidated, interpretation of the clinical meaning of these scores should be done with caution.

  View details for DOI 10.1093/sleepadvances/zpab008

  View details for PubMedID 34250482

• Nonparametric parameters of 24-hour rest-activity rhythms and long-term cognitive decline and incident cognitive impairment in older men. The journals of gerontology. Series A, Biological sciences and medical sciences Xiao, Q., Sampson, J. N., LaCroix, A. Z., Shadyab, A. H., Zeitzer, J. M., Ancoli-Israel, S., Yaffe, K., Stone, K. 2021

  Abstract

  Altered 24-hour rest-activity rhythms may be associated with cognitive impairment in older adults, but evidence from prospective studies is limited. Non-parametric methods were used to assess actigraphy-based activity patterns in 2,496 older men. Incident cognitive impairment was assessed four times over 12 years using the Modified Mini Mental State Examination (3MS) and Trails B tests, self-reported medication use, and clinical diagnosis. The highest quartile (vs. the lowest) of intradaily variability and the lowest quartiles (vs. the highest) of interdaily stability and relative amplitude were associated with incident cognitive impairment ((Hazard ratio (95% confidence interval): 1.82 (1.31, 2.53)), 1.36 (0.99, 1.86), and 1.85 (1.33, 2.56), respectively). A larger increase in intradaily variability over 7.5 years was associated with a greater subsequent decline in 3MS scores but not in Trails B performance. In conclusion, less stable and more variable rest-activity rhythms may represent early biomarkers of cognitive impairment in older men.

  View details for DOI 10.1093/gerona/glab275

  View details for PubMedID 34558603

• Predicting incident dementia and mild cognitive impairment in older women with nonparametric analysis of circadian activity rhythms in the Study of Osteoporotic Fractures. Sleep Posner, A. B., Tranah, G. J., Blackwell, T. n., Yaffe, K. n., Ancoli-Israel, S. n., Redline, S. n., Leng, Y. n., Zeitzer, J. M., Chen, D. M., Webber, K. R., Stone, K. L. 2021

  Abstract

  Disrupted daily rhythms are associated with mild cognitive impairment (MCI) and dementia. The specific nature of how rhythms and cognition are related, however, is unknown. We hypothesized characteristics from a nonparametric estimate of circadian rest-activity rhythm patterns would be associated to the development of MCI or dementia.Wrist actigraphy from 1232 cognitively healthy, community-dwelling women (mean age 82.6 years) from the Study of Osteoporotic Fractures was used to estimate rest-activity patterns, including intradaily variability (IV), interdaily stability (IS), most active 10-hour period (M10), least active 5-hour period (L5), and relative amplitude (RA). Logistic regression examined associations of these predictors with 5-year incidence of MCI or dementia. Models were adjusted for potential confounders.Women with earlier sleep/wake times had higher risk of dementia, but not MCI, (early vs. average L5 midpoint: OR, 1.66; 95% CI, 1.08-2.55) as did women with smaller day/night activity differentials (low vs. high RA: OR, 1.96; 95% CI, 1.14-3.35). IV, IS, and M10 were not associated with MCI or dementia.The timing and difference in day/night amplitude, but not variability of activity, may be useful as predictors of dementia.

  View details for DOI 10.1093/sleep/zsab119

  View details for PubMedID 33964167

• Sleep Problems in Narcolepsy and the Role of Hypocretin/Orexin Deficiency. Frontiers of neurology and neuroscience Mignot, E., Zeitzer, J., Pizza, F., Plazzi, G. 2021; 45: 103-116

  Abstract

  Since its description in the 19th century, narcolepsy type 1 (NT1) has been considered as a model sleep disorder, and after the discovery of rapid eye movement (REM) sleep onset in the disorder, a gateway to understanding REM sleep. The discovery that NT1 is caused by hypocretin/orexin deficiency, together with neurochemical studies of this system, has helped to establish how this neuropeptide regulates the organization of sleep and wake in humans. Current analyses suggest that the main functions of the hypocretin/orexin system are (1) maintenance of wakefulness in the face of moderate sleep deprivation; (2) passive wake promotion, especially in the evening, driven by the circadian clock; (3) inhibition of REM sleep, with possible differential modulating effects on various subcomponents of the sleep-stage, explaining REM sleep dissociation events in NT1. Narcolepsy is also associated with an inability to consolidate sleep, a more complex phenotype that may result from secondary changes or be central to the role of hypocretin in coordinating the activity of other sleep- and wake-promoting systems. Novel technologies, such as the use of deep learning analysis of electroencephalographic signals, is revealing a complex pattern of sleep abnormalities in human narcolepsy that can be used diagnostically. The availability of novel devices measuring sleep 24 h per day also holds promise to provide new insights into how brain electrical activity and muscle tone are regulated by hypocretin.

  View details for DOI 10.1159/000514959

  View details for PubMedID 34052809

• A Temporal Threshold for Distinguishing Off-Wrist from Inactivity Periods: A Retrospective Actigraphy Analysis. Clocks & sleep Lok, R., Zeitzer, J. M. 2020; 2 (4): 466–72

  Abstract

  (1) Background. To facilitate accurate actigraphy data analysis, inactive periods have to be distinguished from periods during which the device is not being worn. The current analysis investigates the degree to which off-wrist and inactive periods can be automatically identified. (2) Methods. In total, 125 actigraphy records were manually scored for 'off-wrist' and 'inactivity' (99 collected with the Motionlogger AMI, 26 (sampling frequency of 60 (n = 20) and 120 (n = 6) s) with the Philips Actiwatch 2.) Data were plotted with cumulative frequency percentage and analyzed with receiver operating characteristic curves. To confirm findings, the thresholds determined in a subset of the Motionlogger dataset (n = 74) were tested in the remaining dataset (n = 25). (3) Results. Inactivity data lasted shorter than off-wrist periods, with 95% of inactive events being shorter than 11 min (Motionlogger), 20 min (Actiwatch 2; 60 s epochs) or 30 min (Actiwatch 2; 120 s epochs), correctly identifying 35, 92 or 66% of the off-wrist periods. The optimal accurate detection of both inactive and off-wrist periods for the Motionlogger was 3 min (Youden's Index (J) = 0.37), while it was 18 (J = 0.89) and 16 min (J = 0.81) for the Actiwatch 2 (60 and 120 s epochs, respectively). The thresholds as determined in the subset of the Motionlogger dataset showed similar results in the remaining dataset. (4) Conclusion. Off-wrist periods can be automatically identified from inactivity data based on a temporal threshold. Depending on the goal of the analysis, a threshold can be chosen to favor inactivity data's inclusion or accurate off-wrist detection.

  View details for DOI 10.3390/clockssleep2040034

  View details for PubMedID 33198122

• ADULT ATTACHMENT PREDICTS DAILY SLEEP VARIATION IN COLORECTAL CANCER PATIENTS Ting, A., Zeitzer, J. M., Wohlgemuth, W., Ramos, A., Madigan, E., Hahn, K., Kim, Y. LIPPINCOTT WILLIAMS & WILKINS. 2020: A216

  View details for Web of Science ID 000549961200588

• ROLE OF ADULT ATTACHMENT AND INTIMACY IN SLEEP IN COLORECTAL CANCER PATIENTS AND SPOUSAL CAREGIVERS Ting, A., Zeitzer, J., Hahn, K., Pedreira, P., Kim, Y. OXFORD UNIV PRESS INC. 2020: S645

  View details for Web of Science ID 000546262401514

• IMPACT OF SUVOREXANT ON TOTAL DAYTIME SLEEP HOURS IN SHIFT WORKERS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL FIELD TRIAL Zeitzer, J. M., Joyce, D. S., Sterkel, A. L., Quevedo, Y. L., Hernandez, B., Holty, J. OXFORD UNIV PRESS INC. 2020: A297

  View details for Web of Science ID 000554588501001

• COMPARATIVE EFFECTIVENESS OF SLEEP APNEA SCREENING TOOLS DURING INPATIENT REHABILITATION FOR MODERATE TO SEVERE TBI Richardson, R., Schwartz, D., Drasher-Phillips, L., Ketchum, J., Calero, K., Dahdah, M., Monden, K., Bell, K., Hoffman, J., Magalang, U., Bogner, J., Whyte, J., Zeitzer, J. OXFORD UNIV PRESS INC. 2020: A231–A232

  View details for Web of Science ID 000554588500606

• Coherence between sleep detection by actigraphy and polysomnography in a multi-center, in-patient cohort of individuals with traumatic brain injury. PM & R : the journal of injury, function, and rehabilitation Zeitzer, J. M., Hon, F., Whyte, J., Monden, K. R., Bogner, J., Dahdah, M., Wittine, L., Bell, K. R., Nakase-Richardson, R. 2020

  Abstract

  INTRODUCTION: Sleep is increasingly recognizes as a crucial component to rapid and successful rehabilitation, especially from traumatic brain injuries (TBI). Assessment of longitudinal patterns of sleep in a hospital setting, however, are difficult and often the expertise or equipment to conduct such studies are not available. Actigraphy (wrist worn accelerometry) has been used for many years as a simple proxy measurement of sleep patterns, but its use has not been thoroughly validated in individuals with TBI.OBJECTIVE: To determine the validity of different sensitivity settings of actigraphy analysis to optimize its use as a proxy for recording sleep patterns in individuals with a traumatic brain injury (TBI).DESIGN: Comparison of actigraphy to criterion standard polysomnographic (PSG)-determination of sleep on a single overnight study.SETTING: Six rehabilitation hospitals in the TBI Model System.PARTICIPANTS: 227 consecutive, medically stable individuals with a TBI.INTERVENTIONS: Not applicable.MAIN OUTCOME MEASURE: Concordance between PSG- and actigraphy-determined sleep using different sensitivity threshold settings (low, medium, high, automated).RESULTS: Bland-Altman plots revealed increasing error with increasing amounts of wake during the sleep episode. Precision-recall statistics indicate that with less sensitive actigraphy thresholds, episodes identified as "wake" are usually 'wake', but many true episodes of 'wake' are missed. With more sensitive actigraphy thresholds, more episodes of 'wake' are identified, but only some of these are true episodes of 'wake'.CONCLUSIONS: In hospitalized patients with TBI and poor sleep, actigraphy underestimates the level of sleep disruption and has poor concordance with PSG-determined sleep. Alternate methods of scoring sleep from actigraphy data are necessary in this population. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/pmrj.12353

  View details for PubMedID 32125095

• PSG Validation of minute-to-minute scoring for sleep and wake periods in a consumer wearable device. PloS one Cheung, J. n., Leary, E. B., Lu, H. n., Zeitzer, J. M., Mignot, E. n. 2020; 15 (9): e0238464

  Abstract

  Actigraphs are wrist-worn devices that record tri-axial accelerometry data used clinically and in research studies. The expense of research-grade actigraphs, however, limit their widespread adoption, especially in clinical settings. Tri-axial accelerometer-based consumer wearable devices have gained worldwide popularity and hold potential for a cost-effective alternative. The lack of independent validation of minute-to-minute accelerometer data with polysomnographic data or even research-grade actigraphs, as well as access to raw data has hindered the utility and acceptance of consumer-grade actigraphs.Sleep clinic patients wore a consumer-grade wearable (Huami Arc) on their non-dominant wrist while undergoing an overnight polysomnography (PSG) study. The sample was split into two, 20 in a training group and 21 in a testing group. In addition to the Arc, the testing group also wore a research-grade actigraph (Philips Actiwatch Spectrum). Sleep was scored for each 60-s epoch on both devices using the Cole-Kripke algorithm.Based on analysis of our training group, Arc and PSG data were aligned best when a threshold of 10 units was used to examine the Arc data. Using this threshold value in our testing group, the Arc has an accuracy of 90.3%±4.3%, sleep sensitivity (or wake specificity) of 95.5%±3.5%, and sleep specificity (wake sensitivity) of 55.6%±22.7%. Compared to PSG, Actiwatch has an accuracy of 88.7%±4.5%, sleep sensitivity of 92.6%±5.2%, and sleep specificity of 60.5%±20.2%, comparable to that observed in the Arc.An optimized sleep/wake threshold value was identified for a consumer-grade wearable Arc trained by PSG data. By applying this sleep/wake threshold value for Arc generated accelerometer data, when compared to PSG, sleep and wake estimates were adequate and comparable to those generated by a clinical-grade actigraph. As with other actigraphs, sleep specificity plateaus due to limitations in distinguishing wake without movement from sleep. Further studies are needed to evaluate the Arc's ability to differentiate between sleep and wake using other sources of data available from the Arc, such as high resolution accelerometry and photoplethysmography.

  View details for DOI 10.1371/journal.pone.0238464

  View details for PubMedID 32941498

• Effect of artificial dawn light on cardiovascular function, alertness, and balance in middle-aged and older adults. Sleep Gabel, V. n., Miglis, M. n., Zeitzer, J. M. 2020

  Abstract

  When arising in the morning, many older people experience dizziness and difficulty maintaining proper balance, as the cardiovascular system is not able to compensate to the postural shift (standing) and maintain sufficient blood flow to the brain. Such changes in cardiovascular function are observed in young individuals exposed to a dawn simulation light. In this study, we examined whether exposure to a dawn simulation light could impact cardiovascular function and consequent changes in balance in middle-aged and older adults.Twenty-three participants (67.3±8.8 y), 12 of whom reported a history of dizziness in the morning, underwent two overnight stays in our laboratory. During both nights, they slept in complete darkness, except for the last 30 minutes of one of the nights during which a dawn simulation light was used. Continuous blood pressure and heart rate were monitored. Subjective and objective alertness, salivary cortisol, and mobile and standing balance were examined upon arising.Dawn simulation light decreased (33%) the amount of sleep before morning awakening, lowered blood pressure (6.24 mmHg), and increased heart rate (0.93 bpm). Despite these changes in physiology, there was no significant impact of dawn simulation on subjective or objective alertness, measures of standing or ambulatory balance, morning cortisol awakening response, or cardiovascular function after awakening.While the dawn simulation did cause an increase in wake and a change in cardiovascular function prior to morning arousal in older adults, we could find no evidence of a functional change in either cardiovascular function or balance upon standing.

  View details for DOI 10.1093/sleep/zsaa082

  View details for PubMedID 32307533

• A comparison of sleep, depressive symptoms, and parental perceptions between U.S. and Taiwan adolescents with self-reported sleep problems. Sleep advances : a journal of the Sleep Research Society Yang, Y., Kaplan, K. A., Zeitzer, J. M. 2020; 1 (1): zpaa004

  Abstract

  Study Objectives: Inadequate sleep is pervasive among teens worldwide, resulting in daytime sleepiness and, in some cases, depressive symptoms. In addition to their own behavioral choices, parent perceptions may also play a role in adolescent sleep. This study conducted a preliminary evaluation of the antecedents and consequences of sleep factors among adolescents in the United States and Taiwan.Methods: Participants were adolescents with self-reported sleep concerns from academically similar schools in Taiwan (n = 548) and northern California, United States (n = 128). Questionnaires on sleep and mood were administered to both the teens and parents.Results: While Taiwanese students' self-reported sleep behavior was generally better than U.S. students (p < .01), Taiwanese students had higher overall self-reported sleepiness (p < .01). Furthermore, Taiwanese parents reported teen sleep durations of 6.53 ± .827 hours per night during the week (with 45% perceiving this as sufficient), while U.S. parents reported teen sleep durations of 7.22 ± .930 hours (with 27% perceiving this as sufficient). Adolescents in both cohorts had high levels of symptoms consistent with depression (Taiwan: 70%, United States: 62%), which was associated with shorter sleep times for both cohorts and evening chronotype in the Taiwanese, but not U.S., adolescents.Conclusions: Some differences exist between Taiwanese and U.S. adolescents, with generally better sleep and less sleepiness reported among students in the United States, and Taiwanese students' sleep influenced more strongly by chronotype. Furthermore, Taiwanese parents reported less concern about their child's insufficient sleep, despite the fact that inadequate sleep is strongly associated with depressive symptoms for both cohorts.

  View details for DOI 10.1093/sleepadvances/zpaa004

  View details for PubMedID 33345187

• Subjective sleep quality is poorly associated with actigraphy and heart rate measures in community-dwelling older men. Sleep medicine Faerman, A. n., Kaplan, K. A., Zeitzer, J. M. 2020; 73: 154–61

  Abstract

  There has been a proliferation in the use of commercially-available accelerometry- and heart rate-based wearable devices to monitor sleep. While the underlying technology is reasonable at detecting sleep quantity, the ability of these devices to predict subjective sleep quality is currently unknown. We tested whether the fundamental signals from such devices are useful in determining subjective sleep quality.Older, community-dwelling men (76.5 ± 5.77 years) enrolled in the Osteoporotic Fractures in Men Study (MrOS) participated in an overnight sleep study during which sleep was monitored with actigraphy (wrist-worn accelerometry) and polysomnography (PSG), including electrocardiography (N = 1141). Subjective sleep quality was determined the next morning using 5-point Likert-type scales of sleep depth and restfulness. Lasso and random forest regression models analyzed the relationship between actigraph-determined sleep variables, the shape of the activity patterns during sleep (functional principal component analysis), average heart rate, heart rate variability (HRV), demographics, and self-reported depression, anxiety, habitual sleep, and daytime sleepiness measures.Actigraphy data, in combination with heart rate, HRV, demographic, and psychological variables, do not predict well subjective sleep quality (R2 = 0.025 to 0.162).Findings are consistent with previous studies that objective sleep measures are not well correlated with subjective sleep quality. Developing validated biomarkers of subjective sleep quality could improve both existing and novel treatment modalities and advance sleep medicine towards precision healthcare standards.

  View details for DOI 10.1016/j.sleep.2020.04.012

  View details for PubMedID 32836083

• Evening salivary cortisol as a single stress marker in women with metastatic breast cancer. Psychoneuroendocrinology Allende, S. n., Medina, J. L., Spiegel, D. n., Zeitzer, J. M. 2020; 115: 104648

  Abstract

  Flattened diurnal salivary cortisol patterns predict shorter subsequent survival with breast, lung, and renal cell carcinomas. The underlying cause of this flattened slope is undetermined, though it has been hypothesized to be secondary to a deficit in the amplitude of the circadian clock. To gain greater insight into the portions of the diurnal salivary curve that are associated with cancer survival, we examined (1) which points in the diurnal curve are predictive of the slope of the curve and (2) whether elevated evening cortisol levels alone are associated with reduced HPA-axis feedback inhibition (i.e., decreased sensitivity to the dexamethasone suppression test).We examined study hypotheses on adult women with advanced breast cancer (age = 54.3 ± 9.58 years; n = 99) using non-parametric Wilcoxon's rank-sum tests, Spearman correlation coefficients and an accuracy formula based on a confusion matrix. Cortisol was sampled five times per day for three consecutive days, with dexamethasone administered late on the second day.Salivary cortisol concentrations did not vary between those with flat and steep slopes during the morning (p's > .05), but did vary in the evening (p's < 0.05). Furthermore, the concentration of the 2100h alone was 86% accurate in discriminating between individuals classified as having "flat" or "steep" slopes. Dexamethasone suppression was only associated with diurnal salivary cortisol slope (p = .0042).Evening cortisol levels are a sensitive indicator flattened diurnal cortisol slope, suggesting evening cortisol may also be a useful predictor of breast cancer survival. Future research should focus on determining the causes of abnormally increased evening cortisol.

  View details for DOI 10.1016/j.psyneuen.2020.104648

  View details for PubMedID 32171899

• RESTLESS LEGS SYNDROME: DOES IT START WITH A GUT FEELING? Blum, D. J., During, E., Barwick, F., Davidenko, P., Zeitzer, J., Parkar, S. ELSEVIER. 2019: S42

  View details for Web of Science ID 000558768400116

• NON-PARAMETRIC ANALYSIS OF REST-ACTIVITY RHYTHMS AND RISK OF INCIDENT MILD COGNITIVE IMPAIRMENT AND DEMENTIA IN OLDER WOMEN Stone, K., Blackwell, T., Yaffe, K., Zeitzer, J., Ancoli-Israel, S., Redline, S., Leng, Y., Tranah, G. ELSEVIER. 2019: S364–S365

  View details for Web of Science ID 000558768401174

• Sleep-wake disorders in Alzheimer's disease: further genetic analyses in relation to objective sleep measures. International psychogeriatrics Yesavage, J. A., Noda, A., Heath, A., McNerney, M. W., Domingue, B. W., Hernandez, Y., Benson, G., Hallmayer, J., O'Hara, R., Williams, L. M., Goldstein-Piekarski, A. N., Zeitzer, J. M., Fairchild, J. K. 2019: 1–7

  Abstract

  This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer's disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.

  View details for DOI 10.1017/S1041610219001777

  View details for PubMedID 31739820

• Comparative Effectiveness of Sleep Apnea Screening Instruments During Inpatient Rehabilitation Following Moderate to Severe TBI. Archives of physical medicine and rehabilitation Nakase-Richardson, R., Schwartz, D. J., Drasher-Phillips, L., Ketchum, J. M., Calero, K., Dahdah, M. N., Monden, K. R., Bell, K., Magalang, U., Hoffman, J., Whyte, J., Bogner, J., Zeitzer, J. M. 2019

  Abstract

  OBJECTIVE: To determine the diagnostic sensitivity and specificity and comparative effectiveness of traditional sleep apnea screening tools in traumatic brain injury (TBI) neurorehabilitation admissions.DESIGN: Prospective diagnostic comparative effectiveness trial of sleep apnea screening tools relative to the gold standard, attended Level 1 polysomnography including encephalography.SETTING: Six TBI Model System Inpatient Rehabilitation Centers PARTICIPANTS: Between 05/2017 and 02/2019, 452 of 896 screened were eligible for the trial with 348 consented (78% consented). Additional screening left 263 eligible for and completing polysomnography with final analyses completed on 248.INTERVENTION: Not applicable.MAIN OUTCOME: Area Under the Curve (AUC) of screening tools relative to total apnea hypopnea index≥15 (AHI, moderate to severe apnea) measured at a median of 47 days post-TBI (IQR 29-47).RESULTS: The Berlin high risk score (ROC-AUC=0.63) was inferior to the MAPI (ROC-AUC = 0.7802) (p=.0211, CI: 0.0181, 0.2233) and STOPBANG (ROC-AUC = 0.7852) (p=.0006, CI: 0.0629, 0.2302); both of which had comparable AUC (p=.7245, CI: -0.0472, 0.0678). Findings were similar for AHI≥30 (severe apnea); however, no differences across scales was observed at AHI>5. The pattern was similar across TBI severity subgroups except for post-traumatic amnesia (PTA) status wherein the MAPI outperformed the Berlin and STOPBANG. Youden's Index to determine risk yielded lower sensitivities but higher specificities relative to non-TBI samples.CONCLUSION: This study is the first to provide clinicians with data to support a choice for which sleep apnea screening tools are more effective during inpatient rehabilitation for TBI (STOPBANG, MAPI vs Berlin) to help reduce comorbidity and possibly improve neurologic outcome.

  View details for DOI 10.1016/j.apmr.2019.09.019

  View details for PubMedID 31705855

• Auditory psychomotor vigilance testing in older and young adults: a revised threshold setting procedure SLEEP AND BREATHING Gabel, V., Kass, M., Joyce, D. S., Spitschan, M., Zeitzer, J. M. 2019; 23 (3): 1021–25

  View details for DOI 10.1007/s11325-019-01859-7

  View details for Web of Science ID 000482433800040

• Optimization of circadian responses with shorter and shorter millisecond flashes. Biology letters Kaladchibachi, S., Negelspach, D. C., Zeitzer, J. M., Fernandez, F. 2019; 15 (8): 20190371

  Abstract

  Recent work suggests that the circadian pacemaker responds optimally to millisecond flashes of light, not continuous light exposure as has been historically believed. It is unclear whether these responses are influenced by the physical characteristics of the pulsing. In the present study, Drosophila (n = 2199) were stimulated with 8, 16 or 120 ms flashes. For each duration, the energy content of the exposure was systematically varied by changing the pulse irradiance and the number of stimuli delivered over a fixed 15 min administration window (64 protocols surveyed in all). Results showed that per microjoule invested, 8 ms flashes were more effective at resetting the circadian activity rhythm than 16- and 120 ms flashes (i.e. left shift of the dose-response curve, as well as a higher estimated maximal response). These data suggest that the circadian pacemaker's photosensitivity declines within milliseconds of light contact. Further introduction of light beyond a floor of (at least) 8 ms leads to diminishing returns on phase-shifting.

  View details for DOI 10.1098/rsbl.2019.0371

  View details for PubMedID 31387472

• Less is More: Ultrashort Light Flashes for Resetting the Human Circadian Clock Zeitzer, J. KARGER. 2019: 173

  View details for Web of Science ID 000496430500053

• Comparison of Alternative Scoring Paradigms of Rest-Activity Consolidation to Inform A Biomarker of Circadian Disruption after TBI Nakase-Richardson, R., Silva, M., Schwartz, D., Calero, K., Zeitzer, J. TAYLOR & FRANCIS LTD. 2019: 19

  View details for Web of Science ID 000466897000046

• The impact of chronotype on prosocial behavior PLOS ONE Solomon, N. L., Zeitzer, J. M. 2019; 14 (4)

  View details for DOI 10.1371/journal.pone.0216309

  View details for Web of Science ID 000466364800043

• PROTEOMIC BIOMARKERS OF CIRCADIAN TIME Ambati, A., Lin, L., Zitting, K., Duffy, J. F., Zeitzer, J., Spiegel, D., Czeisler, C. A., Mignot, E. OXFORD UNIV PRESS INC. 2019

  View details for Web of Science ID 000471071000044

• Feasibility of Actigraphy and Validity in Measuring Sleep during Rehabilitation for Traumatic Brain Injury (vol 99, pg e164, 2018) ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION Silva, M. A., Brennan, E., Schwartz, D. J., Zeitzer, J. M., Nakase-Richardson, R. 2019; 100 (4): 788

  View details for DOI 10.1016/j.apmr.2018.12.012

  View details for Web of Science ID 000462951800035

• A COMPARISON OF MEDICAL-GRADE ACTIGRAPHY DEVICES WITH POLYSOMNOGRAPHY DURING INPATIENT REHABILITATION FOR TRAUMATIC BRAIN INJURY (TBI). Guerrero, G. Y., Schwartz, D., Silva, M. Y., Zeitzer, J., Monden, K., Wittine, L., Bogner, J., Reljic, T., Nakase-Richardson, R. OXFORD UNIV PRESS INC. 2019

  View details for Web of Science ID 000471071003231

• RESTLESS LEG SYNDROME: DOES IT START WITH A GUT FEELING? Blum, D. J., During, E., Barwick, F., Davidenko, P., Zeitzer, J. M. OXFORD UNIV PRESS INC. 2019

  View details for Web of Science ID 000471071000011

• ALTERNATIVE SCORING PARADIGMS OF REST-ACTIVITY CONSOLIDATION (RAC) IN MODERATE TO SEVERE TRAUMATIC BRAIN INJURY (TBI) DURING INPATIENT REHABILITATION Richardson, R., Silva, M., Calero, K., Zeitzer, J. OXFORD UNIV PRESS INC. 2019

  View details for Web of Science ID 000471071002205

• The impact of chronotype on prosocial behavior. PloS one Solomon, N. L., Zeitzer, J. M. 2019; 14 (4): e0216309

  Abstract

  Chronotype (morningness/eveningness) is associated with preference for the timing of many types of behavior, most notably sleep. Chronotype is also associated with differences in the timing of various physiologic events as well as aspects of personality. One aspect linked to personality, prosocial behavior, has not been studied before in the context of chronotype. There are many variables contributing to who, when, and why one human might help another and some of these factors appear fixed, while some change over time or with the environment. It was our intent to examine prosocial behavior in the context of chronotype and environment.Randomly selected adults (N = 100, ages 18-72) were approached in a public space and asked to participate in a study. If the participants consented (n = 81), they completed the reduced Morning-Eveningness Questionnaire and the Stanford Sleepiness Scale, then prosocial behavior was assessed.We found that people exhibited greater prosocial behavior when they were studied further from their preferred time of day. This did not appear to be associated with subjective sleepiness or other environmental variables, such as ambient illumination. This suggests the importance of appreciating the differentiation between the same individual's prosocial behavior at different times of day. Future studies should aim at replicating this result in larger samples and across other measures of prosocial behavior.

  View details for PubMedID 31039208

• Predicting Subjective Sleep Quality Using Recurrent Neural Networks Boussard, J., Kochenderfer, M. J., Zeitzer, J. M., IEEE IEEE. 2019

  View details for Web of Science ID 000565046900023

• Estimating Representative Group Intrinsic Circadian Period from Illuminance-Response Curve Data. Journal of biological rhythms Stack, N. n., Zeitzer, J. M., Czeisler, C. n., Diniz Behn, C. n. 2019: 748730419886992

  Abstract

  The human circadian pacemaker entrains to the 24-h day, but interindividual differences in properties of the pacemaker, such as intrinsic period, affect chronotype and mediate responses to challenges to the circadian system, such as shift work and jet lag, and the efficacy of therapeutic interventions such as light therapy. Robust characterization of circadian properties requires desynchronization of the circadian system from the rest-activity cycle, and these forced desynchrony protocols are very time and resource intensive. However, circadian protocols designed to derive the relationship between light intensity and phase shift, which is inherently affected by intrinsic period, may be applied more broadly. To exploit this relationship, we applied a mathematical model of the human circadian pacemaker with a Markov-Chain Monte Carlo parameter estimation algorithm to estimate the representative group intrinsic period for a group of participants using their collective illuminance-response curve data. We first validated this methodology using simulated illuminance-response curve data in which the intrinsic period was known. Over a physiological range of intrinsic periods, this method accurately estimated the representative intrinsic period of the group. We also applied the method to previously published experimental data describing the illuminance-response curve for a group of healthy adult participants. We estimated the study participants' representative group intrinsic period to be 24.26 and 24.27 h using uniform and normal priors, respectively, consistent with estimates of the average intrinsic period of healthy adults determined using forced desynchrony protocols. Our results establish an approach to estimate a population's representative intrinsic period from illuminance-response curve data, thereby facilitating the characterization of intrinsic period across a broader range of participant populations than could be studied using forced desynchrony protocols. Future applications of this approach may improve the understanding of demographic differences in the intrinsic circadian period.

  View details for DOI 10.1177/0748730419886992

  View details for PubMedID 31779499

• Auditory psychomotor vigilance testing in older and young adults: a revised threshold setting procedure. Sleep & breathing = Schlaf & Atmung Gabel, V. n., Kass, M. n., Joyce, D. S., Spitschan, M. n., Zeitzer, J. M. 2019

  Abstract

  One of the most common ways to examine the daytime impact of sleep loss is the use of the psychomotor vigilance test (PVT). PVT metrics, including median reaction time (RT) and number of lapses, have been examined in a variety of studies in which both acute and chronic sleep times are manipulated. Most of these studies involve young, healthy individuals and use a visual stimulus. As light is a possible countermeasure to sleep loss, and sometimes incompatible with the use of visual PVT, PVT with auditory cues (aPVT) has been used. A threshold of 400 ms is commonly used to delineate lapses from normal RT in the aPVT. As aging can influence a variety of brain functions, we wanted to examine whether this lapse threshold was accurate for use in older adults.Twenty-eight young and 19 healthy older participants performed a 10-min auditory PVT approximately 90 min before habitual bedtime. The occurrence of lapses was determined by five objective RT thresholds: (1) 400 ms, (2) 500 ms, (3) 2 × median, (4) mean + 2 × SD, and (5) method 4 without outliers. Results of these methods were compared with a triplicate visual inspection of RT histograms to determine RT outside of the expected log normal distribution.In both groups, methods 1, 4, and 5 performed poorly, while methods 2 and 3 were adequate, though method 3 was statistically superior.In both age groups, the use of twice the median as an objective threshold had the best concurrence with visual scoring.

  View details for PubMedID 31069648

• Daytime midpoint as a digital biomarker for chronotype in bipolar disorder JOURNAL OF AFFECTIVE DISORDERS Kaufmann, C. N., Gershon, A., Depp, C. A., Miller, S., Zeitzer, J. M., Ketter, T. A. 2018; 241: 586–91

  Abstract

  Bipolar disorder (BD) is associated with later sleep and daily activity (evening rather than morning chronotype). Objective chronotype identification (e.g., based on actigraphs/smartphones) has potential utility, but to date, chronotype has mostly been assessed by questionnaires. Given the ubiquity of accelerometer-based devices (e.g. actigraphs/smartphones) worn/used during daytime and tendency to recharge rather than wear at night, we assessed chronotype using daytime (rather than sleep) interval midpoints.Sixty-one participants with BD type I (BD-I) or II (BD-II) and 61 healthy controls completed 25-50 days of continuous actigraphy. The Composite Scale of Morningness (CSM) was completed by a subset of this group. Daytime activity midpoint was calculated for each daytime interval, excluding naps. Evening chronotype was defined as having a daytime interval midpoint at or after 16:15:00 (4:15:00 PM).BD versus controls had delayed daytime midpoint (mean ± standard deviation) (16:49:07 ± 01:26:19 versus 16:12:51 ± 01:02:14, p < 0.01), and greater midpoint variability (73.3 ± 33.9 min versus 58.1 ± 18.3 min, p < 0.01). Stratifying by gender and age, females and adolescents with BD had delayed and more variable daytime midpoints versus controls. Adults with BD had greater midpoint variability than controls. Within-person mean and standard deviations of daytime midpoints were highly correlated with sleep midpoints (r = 0.99, p < 0.01 and r = 0.86, p < 0.01, respectively). Daytime midpoint mean was also significantly correlated with the CSM (r = -0.56, p < 0.01).Small sample size; analyses not fully accounting for daytime napping.Wrist actigraphy for determination of daytime midpoints is a potential tool to identify objective chronotype. Exploration of the use of consumer devices (wearables/smartphones) is needed.

  View details for PubMedID 30172210

• Morning physiological changes after a dawn simulation light Gabel, V., Zeitzer, J. M. WILEY. 2018

  View details for Web of Science ID 000444228300453

• THE EFFECTS OF CBT-I ON COGNITIVE FUNCTIONING IN INDIVIDUALS WITH INSOMNIA AND MILD COGNITIVE IMPAIRMENT Goldstein-Piekarski, A. N., O'Hora, K., Buchanan, A., Lee, C., Hernandez, B., Zeitzer, J. M., Friedman, L., Kushida, C., Yesavage, J. OXFORD UNIV PRESS INC. 2018: A154–A155

  View details for Web of Science ID 000431183400407

• THE ASSOCIATION OF COGNITIVE FUNCTION WITH 24-HOUR LIGHT EXPOSURE AND ACTIVITY PATTERNS IN OLDER MEN: A PILOT STUDY WITHIN THE MROS SLEEP STUDY Blackwell, T. L., Figueiro, M. G., Jones, G. E., Tranah, G. J., Zeitzer, J. M., Yaffe, K., Ancoli-Israel, S., Stone, K. L. OXFORD UNIV PRESS INC. 2018: A239–A240

  View details for Web of Science ID 000431183400646

• PSG VALIDATION OF MINUTE-TO-MINUTE SCORING FOR SLEEP AND WAKE PERIODS IN A CONSUMER WEARABLE DEVICE Cheung, J., Zeitzer, J., Lu, H., Leary, E., Mignot, E. OXFORD UNIV PRESS INC. 2018: A120–A121

  View details for Web of Science ID 000431183400315

• DAWN SIMULATION AS A PASSIVE COUNTERMEASURE TO MORNING DIZZINESS IN OLDER ADULTS Gabel, Zeitzer, J. M. OXFORD UNIV PRESS INC. 2018: A108–A109

  View details for Web of Science ID 000431183400283

• Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients SUPPORTIVE CARE IN CANCER Kim, Y., Carver, C. S., Hallmayer, J. F., Zeitzer, J. M., Palesh, O., Neri, E., Nouriani, B., Spiegel, D. 2018; 26 (4): 1181–88

  Abstract

  This study tested a theory linking a marker of low serotonergic function to both depression and impulsivity in a sample of advanced breast cancer patients, among whom elevated depressive symptoms and difficulty regulating emotions are commonly reported.A total of 95 patients provided blood samples for serotonin transporter polymorphic region of the gene (5-HTTLPR) and completed questionnaires that measured depressive symptoms and emotional impulsivity.Structural equation modeling revealed that the s allele of 5-HTTLPR was related to greater depressive symptoms (β = .20, p < .042) but only marginally to greater emotional impulsivity (β = .19, p < .068). Depressive symptoms and emotional impulsivity were positively related (β = .33, p < .003). Further tests explored possible mediation from genotype to one psychological variable via the other. Results suggest that depressive symptoms, particularly perceived interpersonal rejection, may be a pathway linking genotype to emotional impulsivity.Findings provide the first evidence that low serotonergic function contributes to both depression and impulsivity within a clinically meaningful sample. Furthermore, the link of s allele of 5-HTTLPR to emotional impulsivity was mediated by depressive symptoms, particularly perceptions of social rejection. Findings have implications for advanced breast cancer patients' treatment decision.

  View details for PubMedID 29090386

• The association between mood state and chronobiological characteristics in bipolar I disorder: a naturalistic, variable cluster analysis-based study INTERNATIONAL JOURNAL OF BIPOLAR DISORDERS Gonzalez, R., Suppes, T., Zeitzer, J., McClung, C., Tamminga, C., Tohen, M., Forero, A., Dwivedi, A., Alvarado, A. 2018; 6: 5

  Abstract

  Multiple types of chronobiological disturbances have been reported in bipolar disorder, including characteristics associated with general activity levels, sleep, and rhythmicity. Previous studies have focused on examining the individual relationships between affective state and chronobiological characteristics. The aim of this study was to conduct a variable cluster analysis in order to ascertain how mood states are associated with chronobiological traits in bipolar I disorder (BDI). We hypothesized that manic symptomatology would be associated with disturbances of rhythm.Variable cluster analysis identified five chronobiological clusters in 105 BDI subjects. Cluster 1, comprising subjective sleep quality was associated with both mania and depression. Cluster 2, which comprised variables describing the degree of rhythmicity, was associated with mania. Significant associations between mood state and cluster analysis-identified chronobiological variables were noted. Disturbances of mood were associated with subjectively assessed sleep disturbances as opposed to objectively determined, actigraphy-based sleep variables. No associations with general activity variables were noted. Relationships between gender and medication classes in use and cluster analysis-identified chronobiological characteristics were noted. Exploratory analyses noted that medication class had a larger impact on these relationships than the number of psychiatric medications in use.In a BDI sample, variable cluster analysis was able to group related chronobiological variables. The results support our primary hypothesis that mood state, particularly mania, is associated with chronobiological disturbances. Further research is required in order to define these relationships and to determine the directionality of the associations between mood state and chronobiological characteristics.

  View details for PubMedID 29457195

• Subjective versus objective evening chronotypes in bipolar disorder Journal of Affective Disorders Gershon, A., Kaufmann, C. N., Depp, C. A., Miller, S., Do, D., Zeitzer, J. M., Ketter, T. A. 2018; 225: 342–349

  Abstract

  Disturbed sleep timing is common in bipolar disorder (BD). However, most research is based upon self-reports. We examined relationships between subjective versus objective assessments of sleep timing in BD patients versus controls.We studied 61 individuals with bipolar I or II disorder and 61 healthy controls. Structured clinical interviews assessed psychiatric diagnoses, and clinician-administered scales assessed current mood symptom severity. For subjective chronotype, we used the Composite Scale of Morningness (CSM) questionnaire, using original and modified (1, ¾, ⅔, and ½ SD below mean CSM score) thresholds to define evening chronotype. Objective chronotype was calculated as the percentage of nights (50%, 66.7%, 75%, or 90% of all nights) with sleep interval midpoints at or before (non-evening chronotype) vs. after (evening chronotype) 04:15:00 (4:15:00a.m.), based on 25-50 days of continuous actigraph data.BD participants and controls differed significantly with respect to CSM mean scores and CSM evening chronotypes using modified, but not original, thresholds. Groups also differed significantly with respect to chronotype based on sleep interval midpoint means, and based on the threshold of 75% of sleep intervals with midpoints after 04:15:00. Subjective and objective chronotypes correlated significantly with one another. Twenty-one consecutive intervals were needed to yield an evening chronotype classification match of ≥ 95% with that made using the 75% of sleep intervals threshold.Limited sample size/generalizability.Subjective and objective chronotype measurements were correlated with one another in participants with BD. Using population-specific thresholds, participants with BD had a later chronotype than controls.

  View details for DOI 10.1016/j.jad.2017.08.055

  View details for PubMedCentralID PMC5626649

• Subjective versus objective evening chronotypes in bipolar disorder. Journal of affective disorders Gershon, A., Kaufmann, C. N., Depp, C. A., Miller, S., Do, D., Zeitzer, J. M., Ketter, T. A. 2018; 225: 342-349

  Abstract

  Disturbed sleep timing is common in bipolar disorder (BD). However, most research is based upon self-reports. We examined relationships between subjective versus objective assessments of sleep timing in BD patients versus controls.We studied 61 individuals with bipolar I or II disorder and 61 healthy controls. Structured clinical interviews assessed psychiatric diagnoses, and clinician-administered scales assessed current mood symptom severity. For subjective chronotype, we used the Composite Scale of Morningness (CSM) questionnaire, using original and modified (1, ¾, ⅔, and ½ SD below mean CSM score) thresholds to define evening chronotype. Objective chronotype was calculated as the percentage of nights (50%, 66.7%, 75%, or 90% of all nights) with sleep interval midpoints at or before (non-evening chronotype) vs. after (evening chronotype) 04:15:00 (4:15:00a.m.), based on 25-50 days of continuous actigraph data.BD participants and controls differed significantly with respect to CSM mean scores and CSM evening chronotypes using modified, but not original, thresholds. Groups also differed significantly with respect to chronotype based on sleep interval midpoint means, and based on the threshold of 75% of sleep intervals with midpoints after 04:15:00. Subjective and objective chronotypes correlated significantly with one another. Twenty-one consecutive intervals were needed to yield an evening chronotype classification match of ≥ 95% with that made using the 75% of sleep intervals threshold.Limited sample size/generalizability.Subjective and objective chronotype measurements were correlated with one another in participants with BD. Using population-specific thresholds, participants with BD had a later chronotype than controls.

  View details for DOI 10.1016/j.jad.2017.08.055

  View details for PubMedID 28843917

  View details for PubMedCentralID PMC5626649

• Correlates of sleep quality in midlife and beyond: a machine learning analysis. Sleep medicine Kaplan, K. A., Hardas, P. P., Redline, S., Zeitzer, J. M. 2017; 34: 162-167

  Abstract

  In older adults, traditional metrics derived from polysomnography (PSG) are not well correlated with subjective sleep quality. Little is known about whether the association between PSG and subjective sleep quality changes with age, or whether quantitative electroencephalography (qEEG) is associated with sleep quality. Therefore, we examined the relationship between subjective sleep quality and objective sleep characteristics (standard PSG and qEEG) across middle to older adulthood.Using cross-sectional analyses of 3173 community-dwelling men and women aged between 39 and 90 participating in the Sleep Heart Health Study, we examined the relationship between a morning rating of the prior night's sleep quality (sleep depth and restfulness) and polysomnographic, and qEEG descriptors of that single night of sleep, along with clinical and demographic measures. Multivariable models were constructed using two machine learning methods, namely lasso penalized regressions and random forests.Little variance was explained across models. Greater objective sleep efficiency, reduced wake after sleep onset, and fewer sleep-to-wake stage transitions were each associated with higher sleep quality; qEEG variables contributed little explanatory power. The oldest adults reported the highest sleep quality even as objective sleep deteriorated such that they would rate their sleep better, given the same level of sleep efficiency. Despite this, there were no major differences in the predictors of subjective sleep across the age span.Standard metrics derived from PSG, including qEEG, contribute little to explaining subjective sleep quality in middle-aged to older adults. The objective correlates of subjective sleep quality do not appear to systematically change with age despite a change in the relationship between subjective sleep quality and objective sleep efficiency.

  View details for DOI 10.1016/j.sleep.2017.03.004

  View details for PubMedID 28522086

• COGNITIVE AROUSAL IN OLDER INDIVIDUALS WITH INSOMNIA COMPLAINTS AROUSAL IN OLDER INDIVIDUALS WITH INSOMNIA COMPLAINTS Friedman, L., Hernandez, B., Buchanan, A., Dinh, M., Cooper, B., Hou, D., Posner, D., Kushida, C., Yesavage, J., Zeitzer, J. M. OXFORD UNIV PRESS INC. 2017: A129

  View details for DOI 10.1093/sleepj/zsx050.345

  View details for Web of Science ID 000433175000346

• VALIDATION OF MINUTE-TO-MINUTE SCORING FOR SLEEP AND WAKE PERIODS IN A CONSUMER WEARABLE DEVICE Cheung, J., Zeitzer, J., Leary, E. B., Mignot, E. OXFORD UNIV PRESS INC. 2017: A288

  View details for DOI 10.1093/sleepj/zsx050.777

  View details for Web of Science ID 000433175000777

• LIGHT FLASHES DURING SLEEP WITH ADJUNCT COGNITIVE BEHAVIORAL THERAPY INCREASES SLEEP IN TEENS Kaplan, K., Mashash, M., Williams, R., Batchelder, H., Starr-Glass, L., Zeitzer, J. OXFORD UNIV PRESS INC. 2017: A337

  View details for DOI 10.1093/sleepj/zsx050.905

  View details for Web of Science ID 000433175001125

• LIGHT AS A COUNTERMEASURE TO THE RISK OF FALLING DURING NOCTURNAL AWAKENINGS Gabel, Zeitzer, J. M. OXFORD UNIV PRESS INC. 2017: A316-A317

  View details for DOI 10.1093/sleepj/zsx050.853

  View details for Web of Science ID 000433175001073

• Eating Decisions Based on Alertness Levels After a Single Night of Sleep Manipulation: A Randomized Clinical Trial. Sleep Pardi, D., Buman, M., Black, J., Lammers, G. J., Zeitzer, J. M. 2017; 40 (2)

  Abstract

  To determine the relationship between an ecologically-relevant change in sleep behavior and its subsequent effects on daytime alertness and feeding behavior.Fifty healthy, young participants (10 male, 40 female) completed two 3-hour study sessions that were at least five days apart. The first session was a baseline evaluation. On the night prior to Session 2, the amount of time in bed was manipulated to be 60%-130% of the individual's habitual sleep time. Within both sessions, subjective (Stanford Sleepiness Scale) and objective (Psychomotor Vigilance Test) alertness were measured. During the middle of each session, a 40-minute ad libitum meal opportunity allowed participants to eat from eight different food items. Food healthfulness, caloric density, distribution, and number of calories were measured and compared to alertness levels.The induced variation in time in bed resulted in induced variation in both subjective and objective (p < .05) measures of alertness. Decreased subjective alertness was associated with increased total caloric consumption (p < .05), and a greater number of calories consumed from less healthy food (p < .05), as rated by both the investigators and by the participant. Decreased objective alertness was associated with less healthy food choices (p < .05), and the consumption of more food from the calorically-dense items (p < .05).Ecologically-relevant impairments in subjective and objective alertness are associated with increased caloric intake and dysfunctional eating decisions. People experiencing reduced alertness after modest sleep loss may be more willing to eat food they recognize as less healthful, and appear to prefer more calorically-dense foods.

  View details for DOI 10.1093/sleep/zsw039

  View details for PubMedID 28364494

• Anatomy and Physiology of the Circadian System SLEEP AND NEUROLOGIC DISEASE Najjar, R. P., Zeitzer, J. M., Miglis, M. G. 2017: 29–53

  View details for DOI 10.1016/B978-0-12-804074-4.00002-9

  View details for Web of Science ID 000422932000004

• Implementation of Actigraphy in Acute Traumatic Brain Injury (TBI) Neurorehabilitation Admissions: A Veterans Administration TBI Model Systems Feasibility Study PM&R Towns, S. J., Zeitzer, J., Kamper, J., Holcomb, E., Silva, M. A., Schwartz, D. J., Nakase-Richardson, R. 2016; 8 (11): 1046-1054

  Abstract

  Sleep problems and disorders are prevalent in patients with traumatic brain injury (TBI) and are associated with negative outcomes. Incidence varies because of challenges including differences in assessment methods, particularly in the acute stages of recovery when patients are cognitively impaired and unable to complete traditional self-report methods. Actigraphy (ACG) recently has been validated in the acute TBI rehabilitation setting and may serve as a superior method of assessing sleep-wake patterns at this stage of recovery. Although a few studies with small sample sizes have described the use of ACG, none have described feasibility and implementation protocols.To describe the feasibility and implementation protocol of ACG to evaluate sleep-wake patterns and white-light exposure data in patients with acute TBI during inpatient rehabilitation. Sleep-wake patterns and light exposure data are presented to characterize the sample using these methods to inform future research.Retrospective study.Acute inpatient rehabilitation unit at a Veterans' Affairs Polytrauma Rehabilitation Center.Veterans (age ≥18 years) admitted to inpatient rehabilitation and enrolled in the Traumatic Brain Injury Model Systems study who were admitted and discharged in the calendar year 2013.Veterans underwent actigraph watch placement as soon as possible after admission. Records from the calendar year 2013 were reviewed to determine the number of admissions that met study criteria and what percentage of those patients had 3 days of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected for the study sample.Percentage of patients who met study criteria and who had 72 hours of continuous ACG data collected. The barriers to successful watch placement in this population were reviewed. Average sleep, light, and wake data from available records were collected.Of 22 eligible Traumatic Brain Injury Model Systems admissions, 3 consecutive nights of ACG data were successfully obtained for 86% (n = 19) of the sample. Barriers to data collection included patient access due to abbreviated lengths of stay, staff availability for ACG placement, and data collection protocols to prevent loss of data in Veterans' Affairs computing systems.ACG is feasible for collecting data about sleep, wake, and light exposure in patients who are in acute TBI inpatient rehabilitation settings.III.

  View details for DOI 10.1016/j.pmrj.2016.04.005

  View details for Web of Science ID 000388553300003

  View details for PubMedID 27178377

• Daily Actigraphy Profiles Distinguish Depressive and Interepisode States in Bipolar Disorder. Clinical psychological science : a journal of the Association for Psychological Science Gershon, A., Ram, N., Johnson, S. L., Harvey, A. G., Zeitzer, J. M. 2016; 4 (4): 641-650

  Abstract

  Disruptions in activity are core features of mood states in bipolar disorder (BD). This study sought to identify activity patterns that discriminate between mood states in BD. Locomotor activity was collected using actigraphy for six weeks in participants with inter-episode BD type I (n=37) or participants with no lifetime mood disorders (n=39). The 24-hour activity pattern of each participant-day was characterized and within-person differences in activity patterns were examined across mood states. Results show that among participants with BD, depressive days are distinguished from other mood states by an overall lower activity level, and a pattern of later activity onset, a midday elevation of activity, and low evening activity. No distinct within-person activity patterns were found for hypomanic/manic days. Since activity can be monitored non-invasively for extended time periods, activity pattern identification may be leveraged to detect mood states in BD, thereby providing more immediate delivery of care.

  View details for PubMedID 27642544

• Indirect Effects of Behavioral Treatment for Insomnia on Depression, Anxiety, Perceived Stress and Telomere Length Yesavage, J. A., Yessengaliyeva, E., Hernandez, B., Noda, A., Thompson, S., Lee, R., Posner, D. A., Lin, J., Neylan, T., Zeitzer, J., Friedman, L. ELSEVIER SCIENCE INC. 2016: S84–S85

  View details for DOI 10.1016/j.jagp.2016.01.081

  View details for Web of Science ID 000408541600072

• Concordance of Actigraphy With Polysomnography in Traumatic Brain Injury Neurorehabilitation Admissions JOURNAL OF HEAD TRAUMA REHABILITATION Kamper, J. E., Garofano, J., Schwartz, D. J., Silva, M. A., Zeitzer, J., Modarres, M., Barnett, S. D., Nakase-Richardson, R. 2016; 31 (2): 117-125

  Abstract

  To examine concordance of accelerometer-based actigraphy (ACG) with polysomnography (PSG) in the determination of sleep states in inpatients with traumatic brain injury (TBI), and examine the impact of injury severity and comorbid conditions (spasticity, apnea) on concordance.This was a convenience sample of 50 participants with primarily severe TBI.This was a retrospective chart review of concurrent administration of PSG with ACG in nonconsecutive rehabilitation admissions with TBI.Total sleep time and sleep efficiency were measured by PSG and ACG.Moderate to strong correlations between ACG and PSG were observed for total sleep time (r = 0.78, P < .01) and sleep efficiency (r = 0.66, P < .01). PSG and ACG estimates of total sleep time (316 minutes vs 325 minutes, respectively) and sleep efficiency (78% vs 77%, respectively) were statistically indistinguishable.Actigraphy is a valid proxy for monitoring of sleep in this population across injury severity and common comorbidity groups. However, further research with larger sample sizes to examine concordance in patients with TBI with disorder of consciousness and spasticity is recommended.

  View details for DOI 10.1097/HTR.0000000000000215

  View details for Web of Science ID 000372981100005

• Concordance of Actigraphy With Polysomnography in Traumatic Brain Injury Neurorehabilitation Admissions. journal of head trauma rehabilitation Kamper, J. E., Garofano, J., Schwartz, D. J., Silva, M. A., Zeitzer, J., Modarres, M., Barnett, S. D., Nakase-Richardson, R. 2016; 31 (2): 117-125

  Abstract

  To examine concordance of accelerometer-based actigraphy (ACG) with polysomnography (PSG) in the determination of sleep states in inpatients with traumatic brain injury (TBI), and examine the impact of injury severity and comorbid conditions (spasticity, apnea) on concordance.This was a convenience sample of 50 participants with primarily severe TBI.This was a retrospective chart review of concurrent administration of PSG with ACG in nonconsecutive rehabilitation admissions with TBI.Total sleep time and sleep efficiency were measured by PSG and ACG.Moderate to strong correlations between ACG and PSG were observed for total sleep time (r = 0.78, P < .01) and sleep efficiency (r = 0.66, P < .01). PSG and ACG estimates of total sleep time (316 minutes vs 325 minutes, respectively) and sleep efficiency (78% vs 77%, respectively) were statistically indistinguishable.Actigraphy is a valid proxy for monitoring of sleep in this population across injury severity and common comorbidity groups. However, further research with larger sample sizes to examine concordance in patients with TBI with disorder of consciousness and spasticity is recommended.

  View details for DOI 10.1097/HTR.0000000000000215

  View details for PubMedID 26959665

• Ubiquity of Undiagnosed Sleep Disordered Breathing in Community-Dwelling Older Male Veterans. American journal of geriatric psychiatry Iqbal, N., Kinoshita, L. M., Noda, A., Friedman, L., Yesavage, J. A., Zeitzer, J. M. 2016; 24 (2): 170-173

  Abstract

  To determine the point prevalence of sleep disordered breathing (SDB) in a community-based sample of older male veterans and to determine if common markers of SDB apply to this population.Two hundred fourteen older male Veterans (age 55-89 years) were recruited for a study on post-traumatic stress disorder and cognitive decline. Questionnaires concerning anthropomorphic and psychological variables were obtained, as was an overnight polysomnographic examination of sleep.Only 13% of the participants lacked clinically meaningful SDB, whereas 33% had moderate SDB and 54% had severe SDB. Being overweight, self-reported snoring, and excessive daytime sleepiness all had good sensitivity (0.86-0.92) but very poor specificity (0.10-0.28) for the prediction of SDB.Undiagnosed SDB was more than threefold higher than expected in these community-dwelling older veterans. Traditional markers of SDB were not specific for predicting clinically relevant SDB.

  View details for DOI 10.1016/j.jagp.2015.08.004

  View details for PubMedID 26778348

• Sleep Disturbance, Diabetes, and Cardiovascular Disease in Postmenopausal Veteran Women GERONTOLOGIST Rissling, M. B., Gray, K. E., Ulmer, C. S., Martin, J. L., Zaslavsky, O., Gray, S. L., Hale, L., Zeitzer, J. M., Naughton, M., Woods, N. F., LaCroix, A., Calhoun, P. S., Stefanick, M., Weitlauf, J. C. 2016; 56: S54-S66

  Abstract

  To compare the prevalence and cardiometabolic health impact of sleep disturbance among postmenopausal Veteran and non-Veteran participants in the Women's Health Initiative (WHI).The prevalence of five categories of sleep disturbance--medication/alcohol use for sleep; risk for insomnia; risk for sleep disordered breathing [SDB]; risk for comorbid insomnia and SDB (insomnia + SDB); and aberrant sleep duration [SLD]--was compared in 3,707 Veterans and 141,354 non-Veterans using logistic or multinomial regression. Cox proportional hazards models were used to evaluate the association of sleep disturbance and incident cardiovascular disease (CVD) and Type 2 diabetes in Veterans and non-Veterans.Women Veterans were more likely to have high risk for insomnia + SDB relative to non-Veteran participants. However, prevalence of other forms of sleep disturbance was similar across groups. Baseline sleep disturbance was not differentially associated with cardiometabolic health outcomes in Veteran versus non-Veteran women. Risks for SDB and insomnia + SDB were both linked to heightened risk of CVD and diabetes; SLD was consistently linked with greater risk of CVD and diabetes in non-Veterans but less strongly and consistently in Veterans.Efforts to identify and treat sleep disturbances in postmenopausal women are needed and may positively contribute to the attenuation of cardiometabolic morbidity risk. Increased awareness of women Veterans' vulnerability to postmenopausal insomnia + SDB may be particularly important for health care providers who treat this population.

  View details for DOI 10.1093/geront/gnv668

  View details for Web of Science ID 000374221500007

  View details for PubMedID 26768391

• Moderators of acupuncture effectiveness in breast cancer survivors: Randomized clinical trial (RCT) Palesh, O., Haddad, N., Schnyer, R., Neri, E., Packer, M., Zeitzer, J. M., Manber, R. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/jco.2016.34.3_suppl.162

  View details for Web of Science ID 000378109500153

• Standing Balance and Spatiotemporal Aspects of Gait Are Impaired Upon Nocturnal Awakening in Healthy Late Middle-Aged and Older Adults JOURNAL OF CLINICAL SLEEP MEDICINE McBean, A. L., Najjar, R. P., Schuchard, R. A., Hall, C. D., Wang, C., Ku, B., Zeitzer, J. M. 2016; 12 (11): 1477-1486

  Abstract

  Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance.Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (< 0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline.Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (F(3,45) = 98.26, p < 0.001). Our a priori hypothesis was confirmed in that variation in stride velocity and center of pressure path length were significantly worse during the mid-sleep awakening compared to presleep baseline. Lighting conditions during the awakening, however, did not influence these parameters. In exploratory analyses, we found that over one-third of the tested gait and balance parameters were significantly worse at the midsleep awakening as compared to baseline (p < 0.05), and nearly one-quarter had medium to large effect sizes (Cohen d ≥ 0.5; r ≥ 0.3).Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights.

  View details for DOI 10.5664/jcsm.6270

  View details for Web of Science ID 000389996700007

  View details for PubMedID 27448415

  View details for PubMedCentralID PMC5078702

• A Bigger Bang for the Buck: Non-Image Forming Responses to Ultra-Short Light Flashes Najjar, R. P., Zeitzer, J. M. KARGER. 2016: 245

  View details for Web of Science ID 000406079500050

• Daily Actigraphy Profiles Distinguish Depressive and Interepisode States in Bipolar Disorder Clinical Psychological Science Gershon, A., Ram, N., Johnson, S. L., Harvey, A. G., Zeitzer, J. M. 2016; 4 (4): 641– 650

  Abstract

  Disruptions in activity are core features of mood states in bipolar disorder (BD). This study sought to identify activity patterns that discriminate between mood states in BD. Locomotor activity was collected using actigraphy for six weeks in participants with inter-episode BD type I (n=37) or participants with no lifetime mood disorders (n=39). The 24-hour activity pattern of each participant-day was characterized and within-person differences in activity patterns were examined across mood states. Results show that among participants with BD, depressive days are distinguished from other mood states by an overall lower activity level, and a pattern of later activity onset, a midday elevation of activity, and low evening activity. No distinct within-person activity patterns were found for hypomanic/manic days. Since activity can be monitored non-invasively for extended time periods, activity pattern identification may be leveraged to detect mood states in BD, thereby providing more immediate delivery of care.

  View details for DOI 10.1177/2167702615604613

  View details for PubMedCentralID PMC5022043

• Aberrant Nocturnal Cortisol as a Vulnerability Trait for More Rapid Progression of Advanced Breast Cancer Zeitzer, J., Nouriani, B., Rissling, M., Sledge, G., Palesh, O., Jo, B., Neri, E., Spiegel, D. NATURE PUBLISHING GROUP. 2015: S194–S195

  View details for Web of Science ID 000366597700347

• RCT utilizing acupuncture for management of insomnia associated with cancer. Palesh, O., Haddad, N., Schnyer, R., Zeitzer, J. M., Neri, E., Manber, R. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for Web of Science ID 000358036904196

• Increased Prevalence of Sleep Disordered Breathing in Older Veterans with PTSD Yesavage, J. A., Iqbal, N., Goodale, G., Noda, A., Hernandez, B., Cheng, J., Zeitzer, J. M., Friedman, L., Kinoshita, L. M. ELSEVIER SCIENCE INC. 2015: S180–S181

  View details for DOI 10.1016/j.jagp.2014.12.189

  View details for Web of Science ID 000350829500181

• Nocturia Reported in Nightly Sleep Diaries: Common Occurrence With Significant Implications? HEALTH PSYCHOLOGY Bliwise, D. L., Friedman, L., Hernandez, B., Zeitzer, J. M., Kushida, C. A., Yesavage, J. A. 2014; 33 (11): 1362-1365

  Abstract

  Nocturia (nocturnal awakenings associated with urination) is so common a nocturnal behavior that its association with poor sleep is often overlooked. This study examined nocturia and its potential role in poor sleep by examining reported nightly awakenings and associated bathroom trips.Sleep diaries were kept by 119 adults with poor sleep for intervals up to 14 days. Diaries collected data on nightly number of awakenings and nightly number of bathroom trips. The proportion of nocturnal awakenings accompanied by voiding for each night was calculated and averaged within each individual. Demographics and various health conditions were examined in relation to this measure.Nocturia was defined when at least two-thirds of all awakenings were associated with nocturnal voiding. Absence of nocturia was defined when less than one-third of awakenings were associated with voiding. Remaining cases were defined as having possible nocturia. Estimates of nocturia derived from prestudy screening were related to nocturia as defined by sleep diaries. Neither gender nor sleep apnea was associated with nocturia. Unadjusted analyses indicated that individuals with nocturia were more likely to have arthritis and attribute their nighttime awakenings to urge to void than individuals without nocturia.Nocturia is an exceedingly common phenomenon and may be associated with multiple morbidities. RESULTS are discussed in terms of causality and whether the perceived urge to void precedes or follows nocturnal awakening. Correlates of nocturia have important implications, because they can inform interventions that target brain (e.g., cognitive-behavioral treatments for insomnia, sedative/hypnotic medications) versus bladder (e.g., bladder control exercises, medications affecting urine production or urgency).

  View details for DOI 10.1037/a0034401

  View details for Web of Science ID 000344010300011

  View details for PubMedCentralID PMC4119089

• Nocturia reported in nightly sleep diaries: common occurrence with significant implications? Health psychology Bliwise, D. L., Friedman, L., Hernandez, B., Zeitzer, J. M., Kushida, C. A., Yesavage, J. A. 2014; 33 (11): 1362-1365

  Abstract

  Nocturia (nocturnal awakenings associated with urination) is so common a nocturnal behavior that its association with poor sleep is often overlooked. This study examined nocturia and its potential role in poor sleep by examining reported nightly awakenings and associated bathroom trips.Sleep diaries were kept by 119 adults with poor sleep for intervals up to 14 days. Diaries collected data on nightly number of awakenings and nightly number of bathroom trips. The proportion of nocturnal awakenings accompanied by voiding for each night was calculated and averaged within each individual. Demographics and various health conditions were examined in relation to this measure.Nocturia was defined when at least two-thirds of all awakenings were associated with nocturnal voiding. Absence of nocturia was defined when less than one-third of awakenings were associated with voiding. Remaining cases were defined as having possible nocturia. Estimates of nocturia derived from prestudy screening were related to nocturia as defined by sleep diaries. Neither gender nor sleep apnea was associated with nocturia. Unadjusted analyses indicated that individuals with nocturia were more likely to have arthritis and attribute their nighttime awakenings to urge to void than individuals without nocturia.Nocturia is an exceedingly common phenomenon and may be associated with multiple morbidities. RESULTS are discussed in terms of causality and whether the perceived urge to void precedes or follows nocturnal awakening. Correlates of nocturia have important implications, because they can inform interventions that target brain (e.g., cognitive-behavioral treatments for insomnia, sedative/hypnotic medications) versus bladder (e.g., bladder control exercises, medications affecting urine production or urgency).

  View details for DOI 10.1037/a0034401

  View details for PubMedID 24245840

• Implementation of objective sleep monitoring during acute neurorehabilitation: Feasibility and clinical findings Nakase-Richardson, R., Schwartz, D., Modarres, M., Zeitzer, J., Anderson, W., Midkiff, M. INFORMA HEALTHCARE. 2014: 770

  View details for Web of Science ID 000335017000615

• Challenges to be overcome using population-based sampling methods to recruit veterans for a study of post-traumatic stress disorder and traumatic brain injury BMC MEDICAL RESEARCH METHODOLOGY Bayley, P. J., Kong, J. Y., Helmer, D. A., Schneiderman, A., Roselli, L. A., Rosse, S. M., Jackson, J. A., Baldwin, J., Isaac, L., Nolasco, M., Blackman, M. R., Reinhard, M. J., Ashford, J. W., Chapman, J. C. 2014; 14

  Abstract

  Many investigators are interested in recruiting veterans from recent conflicts in Afghanistan and Iraq with Traumatic Brain Injury (TBI) and/or Post Traumatic Stress Disorder (PTSD). Researchers pursuing such studies may experience problems in recruiting sufficient numbers unless effective strategies are used. Currently, there is very little information on recruitment strategies for individuals with TBI and/or PTSD. It is known that groups of patients with medical conditions may be less likely to volunteer for clinical research. This study investigated the feasibility of recruiting veterans returning from recent military conflicts--Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF)--using a population-based sampling method.Individuals were sampled from a previous epidemiological study. Three study sites focused on recruiting survey respondents (n = 445) who lived within a 60 mile radius of one of the sites.Overall, the successful recruitment of veterans using a population-based sampling method was dependent on the ability to contact potential participants following mass mailing. Study enrollment of participants with probable TBI and/or PTSD had a recruitment yield (enrolled/total identified) of 5.4%. We were able to contact 146 individuals, representing a contact rate of 33%. Sixty-six of the individuals contacted were screened. The major reasons for not screening included a stated lack of interest in the study (n = 37), a failure to answer screening calls after initial contact (n = 30), and an unwillingness or inability to travel to a study site (n = 10). Based on the phone screening, 36 veterans were eligible for the study. Twenty-four veterans were enrolled, (recruitment yield = 5.4%) and twelve were not enrolled for a variety of reasons.Our experience with a population-based sampling method for recruitment of recent combat veterans illustrates the challenges encountered, particularly contacting and screening potential participants. The screening and enrollment data will help guide recruitment for future studies using population-based methods.

  View details for DOI 10.1186/1471-2288-14-48

  View details for Web of Science ID 000334440800001

  View details for PubMedID 24713131

• Bedtime misalignment and progression of breast cancer. Chronobiology international Hahm, B., Jo, B., Dhabhar, F. S., Palesh, O., Aldridge-Gerry, A., Bajestan, S. N., Neri, E., Nouriani, B., Spiegel, D., Zeitzer, J. M. 2014; 31 (2): 214-221

  Abstract

  Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness-Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes ("going to bed at preferred bedtime") (n = 72), and 46.9 months for women with misaligned bedtimes ("going to bed later or earlier than the preferred bedtime") (n = 13) (log rank p = 0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR = 0.539, 95% CI = 0.320-0.906, p = 0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR = 2.169, 95% CI = 1.124-4.187, p = 0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR = 1.641, 95% CI = 1.000-2.695, p = 0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR = 3.180, 95% CI = 1.327-7.616, p = 0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms.

  View details for DOI 10.3109/07420528.2013.842575

  View details for PubMedID 24156520

• Effects of body mass index-related disorders on cognition: preliminary results. Diabetes, metabolic syndrome and obesity : targets and therapy Yesavage, J. A., Kinoshita, L. M., Noda, A., Lazzeroni, L. C., Fairchild, J. K., Taylor, J., Kulick, D., Friedman, L., Cheng, J., Zeitzer, J. M., O'Hara, R. 2014; 7: 145-151

  Abstract

  Well-known risk factors for cognitive impairment are also associated with obesity. Research has highlighted genetic risk factors for obesity, yet the relationship of those risk factors with cognitive impairment is unknown. The objective of this study was to determine the associations between cognition, hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk factors of obesity were also examined.The sample consisted of 369 nondemented individuals aged 50 years or older from four community cohorts. Primary outcome measures included auditory verbal memory, as measured by the Rey Auditory Verbal Learning Test, and executive functioning, as measured by the Color-Word Interference Test of the Delis-Kaplan Executive Function System battery. Apnea-hypopnea index indicators were determined during standard overnight polysomnography. Statistical analyses included Pearson correlations and linear regressions.Poor executive function and auditory verbal memory were linked to cardiovascular risk factors, but not directly to obesity. Genetic factors appeared to have a small but measureable association to obesity.A direct linkage between obesity and poor executive function and auditory verbal memory is difficult to discern, possibly because nonobese individuals may show cognitive impairment due to insulin resistance and the "metabolic syndrome".

  View details for DOI 10.2147/DMSO.S60294

  View details for PubMedID 24855383

• Randomized controlled trial of pharmacological replacement of melatonin for sleep disruption in individuals with tetraplegia JOURNAL OF SPINAL CORD MEDICINE Zeitzer, J. M., Ku, B., Ota, D., Kiratli, B. J. 2014; 37 (1): 46-53

  Abstract

  To determine the effectiveness of a melatonin agonist for treating sleep disturbances in individuals with tetraplegia.Placebo-controlled, double-blind, crossover, randomized control trial.At home.Eight individuals with tetraplegia, having an absence of endogenous melatonin production and the presence of a sleep disorder. Interventions Three weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover, randomized order) with 2 weeks of baseline prior to and 2 weeks of washout between active conditions.Change in objective and subjective sleep.Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale, SF-36.We observed no consistent changes in either subjective or objective measures of sleep, including subjective sleep latency (P = 0.55, Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35, Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or objective sleep efficiency (P = 0.78, Friedman test). There were significant increases in both objective total sleep time (P < 0.05, Friedman test), subjective time in bed (P < 0.05, Friedman test), and subjective sleep quality (P < 0.05, Friedman test), although these occurred in both arms. There were no significant changes in any of the nine SF-36 subscale scores (Friedman test, Ps >Bonferroni adjusted α of 0.005).In this pilot study, we were unable to show effectiveness of pharmacological replacement of melatonin for the treatment of self-reported sleep problems in individuals with tetraplegia. Trial Registration ClinicalTrials.gov # NCT00507546.

  View details for DOI 10.1179/2045772313Y.0000000099

  View details for Web of Science ID 000337132500007

  View details for PubMedID 24090266

  View details for PubMedCentralID PMC4066551

• Retino-hypothalamic regulation of light-induced murine sleep. Frontiers in systems neuroscience Muindi, F., Zeitzer, J. M., Heller, H. C. 2014; 8: 135-?

  Abstract

  The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area (VLPO) and the suprachiasmatic nucleus (SCN). We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages.

  View details for DOI 10.3389/fnsys.2014.00135

  View details for PubMedID 25140132

  View details for PubMedCentralID PMC4121530

• Effects of body mass index-related disorders on cognition: preliminary results DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY Yesavage, J. A., Kinoshita, L. M., Noda, A., Lazzeroni, L. C., Fairchild, J., Taylor, J., Kulick, D., Friedman, L., Cheng, J., Zeitzer, J. M., O'Hara, R. 2014; 7: 145–51

  View details for DOI 10.2147/DMSO.S60294

  View details for Web of Science ID 000213948100014

• Longitudinal assessment of sleep disordered breathing in Vietnam veterans with post-traumatic stress disorder NATURE AND SCIENCE OF SLEEP Yesavage, J. A., Kinoshita, L. M., Noda, A., Lazzeroni, L. C., Fairchild, J., Friedman, L., Sekhon, G., Thompson, S., Cheng, J., Zeitzer, J. M. 2014; 6: 123–27

  View details for DOI 10.2147/NSS.S65034

  View details for Web of Science ID 000213883600014

• Correspondence of plasma and salivary cortisol patterns in women with breast cancer. Neuroendocrinology Zeitzer, J. M., Nouriani, B., Neri, E., Spiegel, D. 2014; 100 (2-3): 153-161

  Abstract

  The 'diurnal slope' of salivary cortisol has been used as a measure of stress and circadian function in a variety of reports with several detailing its association with cancer progression. The relationship of this slope, typically a negative value from high morning concentrations to low evening concentrations, to the underlying daily variation in total plasma cortisol throughout the 24-hour cycle, however, has never been reported.To examine the relationship between the diurnal salivary cortisol slope and the underlying pattern of plasma cortisol in individuals with cancer, we examined a cohort of women with advanced breast cancer (n = 97) who had saliva and plasma collected during a modified 24-hour, constant posture protocol.We found that the steepness of the diurnal slope of salivary cortisol was correlated with the amplitude of plasma cortisol rhythm when the slope was calculated from samples taken at wake + 30 min and 9 PM (r = -0.29, p > 0.05). Other variants of salivary slope calculations were not significantly correlated with the amplitude of the plasma cortisol rhythm. Diurnal salivary cortisol slope steepness was not correlated with the time between habitual waking and the computed circadian peak of cortisol, but there was a correlation between diurnal slope steepness and the time between habitual waking and the time of the awakening spike of morning cortisol (r values <-0.23, p values <0.05).It therefore appears that in women with advanced breast cancer, diurnal salivary cortisol slope primarily represents aspects of the cortisol awakening response in relation to evening levels more than the circadian rhythm of total plasma cortisol. © 2014 S. Karger AG, Basel.

  View details for DOI 10.1159/000367925

  View details for PubMedID 25228297

  View details for PubMedCentralID PMC4304942

• Longitudinal assessment of sleep disordered breathing in Vietnam veterans with post-traumatic stress disorder. Nature and science of sleep Yesavage, J. A., Kinoshita, L. M., Noda, A., Lazzeroni, L. C., Fairchild, J. K., Friedman, L., Sekhon, G., Thompson, S., Cheng, J., Zeitzer, J. M. 2014; 6: 123-127

  Abstract

  Previous work has demonstrated the relatively high prevalence of risk factors for cognitive impairment, such as sleep disordered breathing (SDB) and obesity, in Vietnam War era veterans with post-traumatic stress disorder (PTSD). No data are currently available on the longitudinal stability of SDB as a risk factor for cognitive decline in that population, which this study now reports.Sample consisted of 48 veterans of the Vietnam War with PTSD who completed longitudinal sleep assessments over a 3-year period. The primary outcome measure, the Apnea-Hypopnea Index (AHI) indicator, was determined during standard overnight polysomnography. Body mass index (BMI) was calculated using standard measurements. Measures of cognitive function tapped auditory verbal memory as measured by the Rey Auditory Verbal Learning Test and executive functioning as measured by the Color-Word Interference Test of the Delis-Kaplan Executive Function System battery. Statistical analyses included mixed effects modeling.In this sample, AHI increased significantly by 2.19 points per year (β=2.19; P<0.005). AHI worsened over the 3-year period, increasing from a mean of 18.7±15.7 to 24.7±17.4 points. Neither BMI nor cognition showed significant change over the 3-year period.SDB worsened in a group of veterans of the Vietnam War with PTSD over a 3-year period. The worsening of SDB over time suggests the need for appropriate countermeasures in populations at risk for progression of the condition.

  View details for DOI 10.2147/NSS.S65034

  View details for PubMedID 25378962

  View details for PubMedCentralID PMC4219637

• Actigraphy-Measured Sleep Disruption as a Predictor of Survival among Women with Advanced Breast Cancer. Sleep Palesh, O., Aldridge-Gerry, A., Zeitzer, J. M., Koopman, C., Neri, E., Giese-Davis, J., Jo, B., Kraemer, H., Nouriani, B., Spiegel, D. 2014; 37 (5): 837-842

  Abstract

  Poor sleep, prevalent among cancer survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Using a prospective research design, this study aimed to clarify the relationship between objective measures of sleep efficiency and sleep disruption with survival among women with advanced breast cancer.We examined sleep quality and duration via wrist-worn actigraphy and sleep diaries for 3 days among 97 women in whom advanced breast cancer was diagnosed (age = 54.6 ± 9.8 years). Sleep efficiency was operationalized using actigraphy as the ratio of total sleep time to total sleep time plus wake after sleep onset.As hypothesized, better sleep efficiency was found to predict a significant reduction in overall mortality (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.98; P < 0.001) at median 6 y follow-up. This relationship remained significant (HR, 0.94; 95% CI, 0.91-0.97; P < 0.001) even after adjusting for other known prognostic factors (age, estrogen receptor status, cancer treatment, metastatic spread, cortisol levels, and depression). Secondary hypotheses were also supported (after adjusting for baseline prognostic factors) showing that less wake after sleep onset (HR, 0.41; 95% CI, 0.25-0.67; P < 0.001), fewer wake episodes, (HR, 0.93; 95% CI, 0.88-0.98; P = 0.007); and shorter wake episode duration (HR, 0.29; 95% CI, 0.14-0.58; P < 0.001) also contributed to reductions in overall mortality.These findings show that better sleep efficiency and less sleep disruption are significant independent prognostic factors in women with advanced breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral and/or pharmacologic therapy could improve survival in women with advanced breast cancer.

  View details for DOI 10.5665/sleep.3642

  View details for PubMedID 24790261

  View details for PubMedCentralID PMC3985107

• Actigraphy Measured Sleep Disruption as a Predictor of Survival Among Women with Advanced Breast Cancer Spiegel, D., Palesh, O., Aldridge-Gerry, A., Zeitzer, J., Koopman, C., Giese-Davis, J., Jo, B., Kraemer, H., Neri, E., Nouriani, B. NATURE PUBLISHING GROUP. 2013: S352–S353

  View details for Web of Science ID 000209477100572

• Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer. Sleep medicine Aldridge-Gerry, A., Zeitzer, J. M., Palesh, O. G., Jo, B., Nouriani, B., Neri, E., Spiegel, D. 2013; 14 (11): 1178-1186

  Abstract

  Sleep disturbance is prevalent among women with metastatic breast cancer (MBC). Our study examined the relationship of depression and marital status to sleep assessed over three nights of polysomnography (PSG).Women with MBC (N=103) were recruited; they were predominately white (88.2%) and 57.8±7.7 years of age. Linear regression analyses assessed relationships among depression, marital status, and sleep parameters.Women with MBC who reported more depressive symptoms had lighter sleep (e.g., stage 1 sleep; P<.05), less slow-wave sleep (SWS) (P<.05), and less rapid eye movement (REM) sleep (P<.05). Single women had less total sleep time (TST) (P<.01), more wake after sleep onset (WASO) (P<.05), worse sleep efficiency (SE) (P<.05), lighter sleep (e.g., stage 1; P<.05), and less REM sleep (P<.05) than married women. Significant interactions indicated that depressed and single women had worse sleep quality than partnered women or those who were not depressed.Women with MBC and greater symptoms of depression had increased light sleep and reduced SWS and REM sleep, and single women had worse sleep quality and greater light sleep than married counterparts. Marriage was related to improved sleep for women with more depressive symptoms.

  View details for DOI 10.1016/j.sleep.2013.07.012

  View details for PubMedID 24074694

• Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer SLEEP MEDICINE Aldridge-Gerry, A., Zeitzer, J. M., Palesh, O. G., Jo, B., Nouriani, B., Neri, E., Spiegel, D. 2013; 14 (11): 1178-1186

  Abstract

  Sleep disturbance is prevalent among women with metastatic breast cancer (MBC). Our study examined the relationship of depression and marital status to sleep assessed over three nights of polysomnography (PSG).Women with MBC (N=103) were recruited; they were predominately white (88.2%) and 57.8±7.7 years of age. Linear regression analyses assessed relationships among depression, marital status, and sleep parameters.Women with MBC who reported more depressive symptoms had lighter sleep (e.g., stage 1 sleep; P<.05), less slow-wave sleep (SWS) (P<.05), and less rapid eye movement (REM) sleep (P<.05). Single women had less total sleep time (TST) (P<.01), more wake after sleep onset (WASO) (P<.05), worse sleep efficiency (SE) (P<.05), lighter sleep (e.g., stage 1; P<.05), and less REM sleep (P<.05) than married women. Significant interactions indicated that depressed and single women had worse sleep quality than partnered women or those who were not depressed.Women with MBC and greater symptoms of depression had increased light sleep and reduced SWS and REM sleep, and single women had worse sleep quality and greater light sleep than married counterparts. Marriage was related to improved sleep for women with more depressive symptoms.

  View details for DOI 10.1016/j.sleep.2013.07.012

  View details for Web of Science ID 000326625400021

  View details for PubMedID 24074694

• A survey study of the association between mobile phone use and daytime sleepiness in California high school students BMC PUBLIC HEALTH Nathan, N., Zeitzer, J. 2013; 13

  Abstract

  Mobile phone use is near ubiquitous in teenagers. Paralleling the rise in mobile phone use is an equally rapid decline in the amount of time teenagers are spending asleep at night. Prior research indicates that there might be a relationship between daytime sleepiness and nocturnal mobile phone use in teenagers in a variety of countries. As such, the aim of this study was to see if there was an association between mobile phone use, especially at night, and sleepiness in a group of U.S. teenagers.A questionnaire containing an Epworth Sleepiness Scale (ESS) modified for use in teens and questions about qualitative and quantitative use of the mobile phone was completed by students attending Mountain View High School in Mountain View, California (n = 211).Multivariate regression analysis indicated that ESS score was significantly associated with being female, feeling a need to be accessible by mobile phone all of the time, and a past attempt to reduce mobile phone use. The number of daily texts or phone calls was not directly associated with ESS. Those individuals who felt they needed to be accessible and those who had attempted to reduce mobile phone use were also ones who stayed up later to use the mobile phone and were awakened more often at night by the mobile phone.The relationship between daytime sleepiness and mobile phone use was not directly related to the volume of texting but may be related to the temporal pattern of mobile phone use.

  View details for DOI 10.1186/1471-2458-13-840

  View details for PubMedID 24028604

• Control of sleep and wakefulness in health and disease. Progress in molecular biology and translational science Zeitzer, J. M. 2013; 119: 137-54

  Abstract

  Sleep and wake are actively promoted states of consciousness that are dependent on a network of state-modulating neurons arising from both the brain stem and hypothalamus. This network helps to coordinate the occurrence of a sleep state in billions of cortical neurons. In many neurological diseases, there is a specific disruption to one of the components of this network. Under conditions of such disruptions, we often gain an improved understanding of the underlying function of the specific component under nonpathological conditions. The loss or dysfunction of one of the hypothalamic or brain stem regions that are responsible for promotion of sleep or wake can lead to disruptions in sleep and wake states that are often subtle, but sometime quite pronounced and of significant medical importance. By understanding the neural substrate and its pathophysiology, one can more appropriately target therapies that might help the specific sleep disruption. This chapter reviews what is currently understood about the neurobiological underpinnings of sleep and wake regulation and how various pathologies evoke changes in these regulatory mechanisms.

  View details for DOI 10.1016/B978-0-12-396971-2.00006-3

  View details for PubMedID 23899597

• The acute effects of light on murine sleep during the dark phase: importance of melanopsin for maintenance of light-induced sleep. European journal of neuroscience Muindi, F., Zeitzer, J. M., Colas, D., Heller, H. C. 2013; 37 (11): 1727-1736

  Abstract

  Light exerts a direct effect on sleep and wakefulness in nocturnal and diurnal animals, with a light pulse during the dark phase suppressing locomotor activity and promoting sleep in the former. In the present study, we investigated this direct effect of light on various sleep parameters by exposing mice to a broad range of illuminances (0.2-200 μW/cm(2) ; equivalent to 1-1000 lux) for 1 h during the dark phase (zeitgeber time 13-14). Fitting the data with a three-parameter log model indicated that ∼0.1 μW/cm(2) can generate half the sleep response observed at 200 μW/cm(2) . We observed decreases in total sleep time during the 1 h following the end of the light pulse. Light reduced the latency to sleep from ~30 min in darkness (baseline) to ~10 min at the highest intensity, although this effect was invariant across the light intensities used. We then assessed the role of melanopsin during the rapid transition from wakefulness to sleep at the onset of a light pulse and the maintenance of sleep with a 6-h 20 μW/cm(2) light pulse. Even though the melanopsin knockout mice had robust induction of sleep (~35 min) during the first hour of the pulse, it was not maintained. Total sleep decreased by almost 65% by the third hour in comparison with the first hour of the pulse in mice lacking melanopsin, whereas only an 8% decrease was observed in wild-type mice. Collectively, our findings highlight the selective effects of light on murine sleep, and suggest that melanopsin-based photoreception is primarily involved in sustaining light-induced sleep.

  View details for DOI 10.1111/ejn.12189

  View details for PubMedID 23510299

• Actigraphy measured sleep disruption as a predictor of survival in advanced breast cancer Palesh, O., Gerry, A., Zeitzer, J. M., Koopman, C., Jo, B., Neri, E., Nouriani, B., Spiegel, D. AMER SOC CLINICAL ONCOLOGY. 2013

  View details for Web of Science ID 000335419603015

• Losing sleep over cancer: Relationships with negative affect, blood pressure, and disease-free interval among women with metastatic breast cancer. Gerry, A., Palesh, O., Rissling, M., Zeitzer, J. M., Dhabhar, F. S., Jo, B., Neri, E., Nouriani, B., Spiegel, D. AMER SOC CLINICAL ONCOLOGY. 2013

  View details for Web of Science ID 000335419602808

• Phenotyping apathy in individuals with Alzheimer disease using functional principal component analysis. American journal of geriatric psychiatry Zeitzer, J. M., David, R., Friedman, L., Mulin, E., Garcia, R., Wang, J., Yesavage, J. A., Robert, P. H., Shannon, W. 2013; 21 (4): 391-397

  Abstract

  To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD).Examination of ad libitum 24-hour ambulatory gross motor activity patterns.Community-dwelling, outpatient.Ninety-two individuals with AD, 35 of whom had apathy.Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA).Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test).There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

  View details for DOI 10.1016/j.jagp.2012.12.012

  View details for PubMedID 23498386

• CANCER PROGRESSION AND ALTERATIONS OF SLEEP ARCHITECTURE IN WOMEN WITH METASTATIC BREAST CANCER Aldridge-Gerry, A., Zeitzer, J., Palesh, O., Dhabhar, F., Jo, B., Neri, E., Nouriani, B., Spiegel, D. SPRINGER. 2013: S159

  View details for Web of Science ID 000209928001199

• NATURAL KILLER (NK) CELL DIURNAL RHYTHMS AND SLEEP DISRUPTION IN METASTATIC BREAST CANCER Dhabhar, F. S., Jo, B., Neri, E., Zeitzer, J., Bricker, N. M., Nouriani, B., Aldridge-Gerry, A., Spiegel, D. SPRINGER. 2013: S160

  View details for Web of Science ID 000209928001201

• OBESITY IN WOMEN WITH METASTATIC BREAST CANCER IS ASSOCIATED WITH DISRUPTED CIRCADIAN RHYTHMS, POOR SLEEP, DEPRESSION AND REDUCED PHYSICAL ACTIVITY Palesh, O., Koopman, C., Zeitzer, J., Aldridge-Gerry, A., Neri, E., Mustian, K., Nouriani, B., Spiegel, D. SPRINGER. 2013: S160

  View details for Web of Science ID 000209928001200

• Nocturia Compounds Nocturnal Wakefulness in Older Individuals with Insomnia JOURNAL OF CLINICAL SLEEP MEDICINE Zeitzer, J. M., Bliwise, D. L., Hernandez, B., Friedman, L., Yesavage, J. A. 2013; 9 (3): 259-262

  Abstract

  To determine the impact of nocturia on objective measures of sleep in older individuals with insomnia.The sleep and toileting patterns of a group of community-dwelling older men (n = 55, aged 64.3 ± 7.52 years) and women (n = 92, aged 62.5 ± 6.73 years) with insomnia were studied for two weeks using sleep logs and one week using actigraphy. The relationships between nocturia and various sleep parameters were analyzed with ANOVA and linear regression.More than half (54.2% ± 39.9%) of all log-reported nocturnal awakenings were associated with nocturia. A greater number of trips to the toilet was associated with worse log-reported restedness (p < 0.01) and sleep efficiency (p < 0.001), as well as increases in actigraph-derived measures of the number and length of nocturnal wake bouts (p < 0.001) and wake after sleep onset (p < 0.001). Actigraph-determined wake bouts were 11.5% ± 23.5% longer on nights on which there was a trip to the toilet and wake after sleep onset was 20.8% ± 33.0% longer during these nights.Nocturia is a common occurrence in older individuals with insomnia and is significantly associated with increased nocturnal wakefulness and decreased subjective restedness after sleep.

  View details for DOI 10.5664/jcsm.2492

  View details for Web of Science ID 000316209800010

  View details for PubMedID 23493881

  View details for PubMedCentralID PMC3578689

• Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD SLEEP AND BREATHING Kinoshita, L. M., Yesavage, J. A., Noda, A., Jo, B., Hernandez, B., Taylor, J., Zeitzer, J. M., Friedman, L., Fairchild, J. K., Cheng, J., Kuschner, W., O'Hara, R., Holty, J. C., Scanlon, B. K. 2012; 16 (4): 1201-1209

  Abstract

  The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults.The PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea-hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO(2), mean SpO(2)) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed.In regression models, AHI (β = -4.099; p < 0.01) and hypertension (β = -4.500; p < 0.05) predicted RAVLT; hypertension alone (β = 9.146; p < 0.01) predicted CWIT. ROC analyses selected min SpO(2) cut-points of 85% for RAVLT (κ = 0.27; χ² = 8.23, p < 0.01) and 80% for CWIT (κ = 0.25; χ² = 12.65, p < 0.01). Min SpO(2) cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO(2), β = 4.452; p < 0.05; hypertension, β = -4.332; p < 0.05), and in separate models for CWIT (min SpO(2), β = -8.286; p < 0.05; hypertension, β = -8.993; p < 0.01).OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.

  View details for DOI 10.1007/s11325-011-0632-8

  View details for Web of Science ID 000311301700038

  View details for PubMedID 22193972

• Decreased Daytime Motor Activity Associated With Apathy in Alzheimer Disease: An Actigraphic Study AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY David, R., Mulin, E., Friedman, L., Le Duff, F., Cygankiewicz, E., Deschaux, O., Garcia, R., Yesavage, J. A., Robert, P. H., Zeitzer, J. M. 2012; 20 (9): 806-814

  Abstract

  Across all stages of Alzheimer disease (AD), apathy is the most common neuropsychiatric symptom. Studies using the Neuropsychiatric Inventory (NPI) have found that apathy is present in up to 70% of individuals with Alzheimer disease. One of the main difficulties in assessing apathy and other neuropsychiatric symptoms is the absence of reliable, objective measures. Motor activity assessment using ambulatory actigraphy could provide an indirect, objective evaluation of apathy. The aim of our study was to assess the relationship between apathy and daytime motor activity in AD, using ambulatory actigraphy.One hundred seven AD outpatients wore a wrist actigraph (Motionlogger) during seven consecutive 24-hour periods to evaluate motor activity. Participants were divided into two subgroups according to their apathy subscores on the NPI: individuals with apathy (NPI-apathy subscores >4) and those without. Daytime mean motor activity scores were compared between the two subgroups.Individuals with AD who had symptoms of apathy (n = 43; age = 79 ± 4.7 years; Mini-Mental State Examination = 20.9 ± 4.8) had significantly lower daytime mean motor activity than AD patients without apathy (n = 64; age = 76.3 ± 7.7; Mini-Mental State Examination = 21.5 ± 4.7), while nighttime mean motor activity did not significantly differ between the two subgroups.Ambulatory actigraphy could be added to currently used questionnaires as a simple, objective technique for assessing apathy in the routine assessment of AD patients.

  View details for DOI 10.1097/JGP.0b013e31823038af

  View details for Web of Science ID 000308078500010

  View details for PubMedID 21997602

• Psychosocial correlates of sleep architecture in women with advanced breast cancer. 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Gerry, A. A., Jo, B., Palesh, O., Zeitzer, J., Neri, E., Spiegel, D. AMER SOC CLINICAL ONCOLOGY. 2012

  View details for Web of Science ID 000318009800188

• Brief morning light treatment for sleep/wake disturbances in older memory-impaired individuals and their caregivers SLEEP MEDICINE Friedman, L., Spira, A. P., Hernandez, B., Mather, C., Sheikh, J., Ancoli-Israel, S., Yesavage, J. A., Zeitzer, J. M. 2012; 13 (5): 546-549

  Abstract

  Scheduled exposure to bright light (phototherapy) has been used, with varying degrees of success, to treat sleep disruption in older individuals. Most of these studies have been done in institutional settings and have used several hours of daily light exposure. Such a regimen in the home setting may be untenable, especially when the individual with the sleep disruption has memory impairment and is being cared for by a family member. As such, we examined the effectiveness of a "user-friendly" phototherapy protocol that would be readily usable in the home environment.We exposed a group of 54 older caregiver/care recipient dyads, in which the care recipient had memory impairment, to two weeks of morning bright light phototherapy. Dyads were exposed to either bright white (∼4200 lux) or dim red (∼90 lux) light for 30 min every day, starting within 30 min of rising. All subjects also received sleep hygiene therapy. Objective (actigraphy) and subjective measures of sleep and mood were obtained at baseline and at the end of the two weeks of phototherapy.In care recipients, actigraphy- and log-determined time in bed and total sleep time declined in the active condition (p<0.05, ANOVA); there was no corresponding change in subjective insomnia symptoms (p's>0.37, ANOVA). The decrease in the time in bed was associated with an earlier out of bed time in the morning (p<0.001, Pearson correlation). The decrease in the total sleep time was associated with a decrease in sleep efficiency (p<0.001, Pearson correlation) and an increase in wake after sleep onset (p<0.001, Pearson correlation). In caregivers, there were no differential changes in actigraphic measures of sleep (p's>0.05, ANOVA). Actigraphy-measured wake after sleep onset and sleep efficiency did, however, improve in both conditions, as did sleepiness, insomnia symptoms, and depressive symptomatology (p's<0.05, ANOVA).Exposure to this regimen of phototherapy diminished sleep in older individuals with memory impairments. Their caregivers, however, experienced an improvement in sleep and mood that appeared independent of the phototherapy and likely due to participation in this protocol or the sleep hygiene therapy.

  View details for DOI 10.1016/j.sleep.2011.11.013

  View details for Web of Science ID 000303346800016

  View details for PubMedID 22406033

  View details for PubMedCentralID PMC3337852

• Time-course of cerebrospinal fluid histamine in the wake-consolidated squirrel monkey JOURNAL OF SLEEP RESEARCH Zeitzer, J. M., Kodama, T., Buckmaster, C. L., Honda, Y., Lyons, D. M., Nishino, S., Mignot, E. 2012; 21 (2): 189-194

  Abstract

  Central nervous system (CNS) histamine is low in individuals with narcolepsy, a disease characterized by severe fragmentation of both sleep and wake. We have developed a primate model, the squirrel monkey, with which we can examine the role of the CNS in the wake-consolidation process, as these primates are day-active, have consolidated wake and sleep and have cerebrospinal fluid (CSF) that is readily accessible. Using this model and three distinct protocols, we report herein on the role of CNS histamine in the wake consolidation process. CSF histamine has a robust daily rhythm, with a mean of 24.9 ± 3.29 pg mL(-1) , amplitude of 31.7 ± 6.46 pg mL(-1) and a peak at 17:49 ± 70.3 min (lights on 07:00-19:00 hours). These levels are not significantly affected by increases (up to 161 ± 40.4% of baseline) or decreases (up to 17.2 ± 2.50% of baseline) in locomotion. In direct contrast to the effects of sleep deprivation in non-wake-consolidating mammals, in whom CSF histamine increases, pharmacologically induced sleep (γ-hydroxybutyrate) and wake (modafinil) have no direct effects on CSF histamine concentrations. These data indicate that the time-course of histamine in CSF in the wake-consolidated squirrel monkey is robust against variation in activity and sleep and wake-promoting pharmacological compounds, and may indicate that histamine physiology plays a role in wake-consolidation such as is present in the squirrel monkey and humans.

  View details for DOI 10.1111/j.1365-2869.2011.00957.x

  View details for Web of Science ID 000301931500010

  View details for PubMedID 21910776

  View details for PubMedCentralID PMC3237761

• Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: Preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep SLEEP MEDICINE Nova, P., Hernandez, B., Ptolemy, A. S., Zeitzer, J. M. 2012; 13 (4): 362-367

  Abstract

  To examine the validity of a novel caffeine intake questionnaire and to examine the effects of caffeine on sleep in college students.One-week, ad libitum behavior of 50 university students (28 female, 22 male; aged 20.9 ± 1.78 years) was examined with sleep logs, wrist actigraphy, and a novel daily questionnaire assessing caffeine intake at different times of day. Saliva samples were collected for caffeine assessment (questionnaire validation) and DNA extraction, and for analysis of a single nucleotide polymorphism in the adenosine receptor 2A (ADORA2A) gene.The caffeine questionnaire was able to accurately predict salivary concentrations of caffeine (R(2) = 0.41, P<0.001). Estimations of integrated salivary caffeine concentration during sleep were correlated with wake after sleep onset (WASO) most strongly in morning-type individuals (R(2) = 0.49; P<0.001, ANOVA), less so in intermediate chronotypes (R(2) = 0.16; P<0.001, ANOVA), and not significantly in evening-types (R(2) = 0.00098; P = 0.13, ANOVA). Using multivariate modeling methods we found that the ADORA2A genotype did not moderate the effects of caffeine on WASO, but did independently alter WASO such that those with the CC genotype had nearly three-times as much WASO as those with CT or TT.Our questionnaire was able to accurately predict salivary caffeine concentrations and helped to describe a novel relationship between the effects of caffeine on sleep and genotype and chronotype.

  View details for DOI 10.1016/j.sleep.2011.11.011

  View details for Web of Science ID 000303346300007

  View details for PubMedID 22333316

• Sleep-Disordered Breathing in Vietnam Veterans with Posttraumatic Stress Disorder AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yesavage, J. A., Kinoshita, L. M., Kimball, T., Zeitzer, J., Friedman, L., Noda, A., David, R., Hernandez, B., Lee, T., Cheng, J., O'Hara, R. 2012; 20 (3): 199-204

  Abstract

  : To study the prevalence of sleep-disordered breathing (SDB) in Vietnam- era veterans.: This was an observational study of Vietnam-era veterans using unattended, overnight polysomnography, cognitive testing, and genetic measures.: A sample of 105 Vietnam-era veterans with posttraumatic stress disorder: 69% had an Apnea Hypopnea Index >10. Their mean body mass index was 31, "obese" by Centers for Disease Control and Prevention criteria, and body mass index was significantly associated with Apnea Hypopnea Index (Spearman r = 0.41, N = 97, p < 0.0001). No significant effects of sleep-disordered breathing or apolipoprotein status were found on an extensive battery of cognitive tests.: There is a relatively high prevalence of SDB in these patients which raises the question of to what degree excess cognitive loss in older PTSD patients may be due to a high prevalence of SDB.

  View details for DOI 10.1097/JGP.0b013e3181e446ea

  View details for Web of Science ID 000300642300002

  View details for PubMedID 20808112

• Phenotyping Apathy in Individuals With Alzheimer Disease Using Functional Principal Component Analysis. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Zeitzer, J. M., David, R., Friedman, L., Mulin, E., Garcia, R., Wang, J., Yesavage, J. A., Robert, P. H., Shannon, W. 2012

  Abstract

  OBJECTIVES:: To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD). DESIGN:: Examination of ad libitum 24-hour ambulatory gross motor activity patterns. SETTING:: Community-dwelling, outpatient. PARTICIPANTS:: Ninety-two individuals with AD, 35 of whom had apathy. MEASUREMENTS:: Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA). RESULTS:: Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test). CONCLUSIONS:: There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.

  View details for DOI 10.1097/JGP.0b013e318248779d

  View details for PubMedID 22367164

  View details for PubMedCentralID PMC3368995

• Lower peak numbers, blunted diurnal rhythms of immune cell distribution, and sleep disruption in metastatic breast cancer Dhabhar, F. S., Jo, B., Neri, E., Zeitzer, J., Tillie, J. M., Bricker, N. M., Nouriani, B., Spiegel, D. CO-ACTION PUBLISHING. 2012

  View details for DOI 10.3402/ejpt.v3i0.19487

  View details for Web of Science ID 000208868500013

• LIGHT FLASHES PHASE SHIFT HUMAN CIRCADIAN RHYTHMS DURING AND WITHOUT DISTURBING SLEEP Zeitzer, J., Ruby, N. F., Heller, H. OXFORD UNIV PRESS INC. 2012: A63

  View details for Web of Science ID 000312996500173

• INDIVIDUAL DIFFERENCE FACTORS IN FLIGHT CONTROL AND DECISION MAKING PERFORMANCE Kennedy, Q., Taylor, J. L., Yesavage, J., Noda, A., Adamson, M. M., Murphy, G., Zeitzer, J. M. OXFORD UNIV PRESS INC. 2011: 552

  View details for Web of Science ID 000303602003510

• Effectiveness of evening phototherapy for insomnia is reduced by bright daytime light exposure SLEEP MEDICINE Zeitzer, J. M., Friedman, L., Yesavage, J. A. 2011; 12 (8): 805-807

  Abstract

  To examine the effect of ambulatory daytime light exposure on phase delays and on the advances produced by timed exposure to bright evening or morning light.As a subset of a larger study, 32 older (63.0 ± 6.43 years) adults with primary insomnia were randomized to an at-home, single-blind, 12-week, parallel-group study entailing daily exposure to 45 min of scheduled evening or morning bright (∼4000 lux) light. Light exposure patterns during the baseline and the last week of treatment were monitored using actigraphs with built-in illuminance detectors. Circadian phase was determined through analysis of in-laboratory collected plasma melatonin.Less daytime light exposure during the last week of treatment was significantly associated with larger phase delays in response to evening light (r's>0.78). Less daytime light exposure during the last week of treatment was also associated with a significant delay in wake time (r's>-0.75). There were no such relationships between light exposure history and phase advances in response to morning light.Greater light exposure during the daytime may decrease the ability of evening light, but not morning light, exposure to engender meaningful changes of circadian phase.

  View details for DOI 10.1016/j.sleep.2011.02.005

  View details for Web of Science ID 000295764800013

  View details for PubMedID 21855408

  View details for PubMedCentralID PMC3176957

• The Roles of COMT val158met Status and Aviation Expertise in Flight Simulator Performance and Cognitive Ability BEHAVIOR GENETICS Kennedy, Q., Taylor, J. L., Noda, A., Adamson, M., Murphy, G. M., Zeitzer, J. M., Yesavage, J. A. 2011; 41 (5): 700-708

  Abstract

  The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41-69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task.

  View details for DOI 10.1007/s10519-010-9436-z

  View details for Web of Science ID 000294297200008

  View details for PubMedID 21193954

  View details for PubMedCentralID PMC3163820

• Initial Cognitive Performance Predicts Longitudinal Aviator Performance JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J. A., Jo, B., Adamson, M. M., Kennedy, Q., Noda, A., Hernandez, B., Zeitzer, J. M., Friedman, L. F., Fairchild, K., Scanlon, B. K., Murphy, G. M., Taylor, J. L. 2011; 66 (4): 444-453

  Abstract

  The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age.We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise.Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age.These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.

  View details for DOI 10.1093/geronb/gbr031

  View details for Web of Science ID 000293251900007

  View details for PubMedID 21586627

  View details for PubMedCentralID PMC3132267

• Circadian Clock Gene Polymorphisms and Sleep-Wake Disturbance in Alzheimer Disease AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY Yesavage, J. A., Noda, A., Hernandez, B., Friedman, L., Cheng, J. J., Tinklenberg, J. R., Hallmayer, J., O'Hara, R., David, R., Robert, P., Landsverk, E., Zeitzer, J. M. 2011; 19 (7): 635-643

  Abstract

  One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes.One week of ad libitum ambulatory sleep data collection.At-home collection of sleep data and in-laboratory questionnaire.Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimer's Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimer's Disease Neuroimaging Initiative data set.Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined.Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance.It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

  View details for DOI 10.1097/JGP.0b013e31820d92b2

  View details for PubMedID 21709609

• Faster REM sleep EEG and worse restedness in older insomniacs with HLA DQB1*0602 PSYCHIATRY RESEARCH Zeitzer, J. M., Fisicaro, R. A., Grove, M. E., Mignot, E., Yesavage, J. A., Friedman, L. 2011; 187 (3): 397-400

  Abstract

  HLA DQB1*0602 is found in most individuals with hypocretin-deficient narcolepsy, a disorder characterized by a severe disruption of sleep and wake. Population studies indicate that DQB1*0602 may also be associated with normal phenotypic variation of rapid eye movement (REM) sleep. Disruption of REM sleep has been linked to specific symptoms of insomnia. We here examine the relationship of sleep and DQB1*0602 in older individuals (n=46) with primary insomnia, using objective (polysomnography, wrist actigraphy) and subjective (logs, scales) measures. DQB1*0602 positivity was similarly distributed in the older individuals with insomnia (24%) as in the general population (25%). Most sleep variables were statistically indistinguishable between DQB1*0602 positive and negative subjects except that those with the allele reported that they were significantly less well rested than those without it. When sleep efficiencies were lower than 70%, DQB1*0602 positive subjects reported being less well rested at the same sleep efficiency than those without the allele. Examination of EEG during REM sleep also revealed that DQB1*0602 positive subjects had EEG shifted towards faster frequencies compared with negative subjects. Thus, DQB1*0602 positivity is associated with both a shift in EEG power spectrum to faster frequencies during REM sleep and a diminution of restedness given the same sleep quantity.

  View details for DOI 10.1016/j.psychres.2011.01.007

  View details for Web of Science ID 000290506500014

  View details for PubMedID 21292329

  View details for PubMedCentralID PMC3079052

• Exposure to Room Light before Bedtime Suppresses Melatonin Onset and Shortens Melatonin Duration in Humans JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Gooley, J. J., Chamberlain, K., Smith, K. A., Khalsa, S. B., Rajaratnam, S. M., Van Reen, E., Zeitzer, J. M., Czeisler, C. A., Lockley, S. W. 2011; 96 (3): E463-E472

  Abstract

  Millions of individuals habitually expose themselves to room light in the hours before bedtime, yet the effects of this behavior on melatonin signaling are not well recognized.We tested the hypothesis that exposure to room light in the late evening suppresses the onset of melatonin synthesis and shortens the duration of melatonin production.In a retrospective analysis, we compared daily melatonin profiles in individuals living in room light (<200 lux) vs. dim light (<3 lux).Healthy volunteers (n = 116, 18-30 yr) were recruited from the general population to participate in one of two studies.Participants lived in a General Clinical Research Center for at least five consecutive days.Individuals were exposed to room light or dim light in the 8 h preceding bedtime.Melatonin duration, onset and offset, suppression, and phase angle of entrainment were determined.Compared with dim light, exposure to room light before bedtime suppressed melatonin, resulting in a later melatonin onset in 99.0% of individuals and shortening melatonin duration by about 90 min. Also, exposure to room light during the usual hours of sleep suppressed melatonin by greater than 50% in most (85%) trials.These findings indicate that room light exerts a profound suppressive effect on melatonin levels and shortens the body's internal representation of night duration. Hence, chronically exposing oneself to electrical lighting in the late evening disrupts melatonin signaling and could therefore potentially impact sleep, thermoregulation, blood pressure, and glucose homeostasis.

  View details for DOI 10.1210/jc.2010-2098

  View details for Web of Science ID 000288020600005

  View details for PubMedID 21193540

  View details for PubMedCentralID PMC3047226

• Association between COMT Polymorphisms and Apathy in Alzheimer's Disease Renaud, D., Friedman, L., Mulin, E., Noda, A., Le Duff, F., Garcia, R., Kennedy, Q., Robert, P. H., Yesavage, J. A., Zeitzer, J. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: A414

  View details for Web of Science ID 000288149302204

• Lack of Association Between COMT Polymorphisms and Apathy in Alzheimer's Disease JOURNAL OF ALZHEIMERS DISEASE David, R., Friedman, L., Mulin, E., Noda, A., Le Duff, F., Kennedy, Q., Garcia, R., Robert, P. H., Yesavage, J. A., Zeitzer, J. M. 2011; 27 (1): 155-161

  Abstract

  We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer's disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age = 79.3 ± 7.03 years; MMSE = 20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD.

  View details for DOI 10.3233/JAD-2011-110491

  View details for Web of Science ID 000296570400014

  View details for PubMedID 21785189

• MILLISECOND LIGHT FLASHES PHASE SHIFT HUMAN CIRCADIAN RHYTHMS Zeitzer, J., Ruby, N. F., Heller, H. OXFORD UNIV PRESS INC. 2011: A56

  View details for Web of Science ID 000299834400154

• DIFFERENTIAL EFFECTS OF MORNING LIGHT TREATMENT COMBINED WITH SLEEP HYGIENE THERAPY ON MEMORY-IMPAIRED INDIVIDUALS AND THEIR CAREGIVERS Friedman, L. F., Spira, A. P., Hernandez, B., Sheikh, J., Yesavage, J. A., Zeitzer, J. OXFORD UNIV PRESS INC. 2011: A217

  View details for Web of Science ID 000299834400627

• FUNCTIONAL PRINCIPAL COMPONENT ANALYSIS REVEALS DISRUPTED ACTIVITY RHYTHM IN INDIVIDUALS WITH ALZHEIMER'S DISEASE AND APATHY Zeitzer, J., David, R., Friedman, L. F., Mulin, E., Wang, J., Robert, P. H., Shannon, W. OXFORD UNIV PRESS INC. 2011: A249

  View details for Web of Science ID 000299834400724

• Relationship between Apathy and Sleep Disturbance in Mild and Moderate Alzheimer's Disease: An Actigraphic Study JOURNAL OF ALZHEIMERS DISEASE Mulin, E., Zeitzer, J. M., Friedman, L., Le Duff, F., Yesavage, J., Robert, P. H., David, R. 2011; 25 (1): 85-91

  Abstract

  Apathy is the most frequently reported neuropsychiatric symptom across all stages of Alzheimer's disease (AD). Both apathy and sleep disorders are known to have independent negative effects on the quality of life in individuals with AD. The aim of this study was to assess the relationship between apathy and sleep/wake patterns in individuals with AD using ambulatory actigraphy. One hundred and three non-institutionalized individuals with AD wore a wrist actigraph continuously over seven consecutive 24-h periods. Apathy was assessed using the Neuropsychiatric Inventory. Daytime mean motor activity (dMMA) was calculated from daytime wrist actigraphy data. Actigraphic parameters of sleep included total sleep time (TST), wake after sleep onset (WASO), time in bed (TIB), WASO normalized by TIB, sleep latency, and nighttime mean motor activity (nMMA). Among the 103 individuals with AD (aged 76.9 ± 7.2 years; MMSE = 21.4 ± 4.3), those with apathy had significantly lower dMMA, higher WASO (both raw and normalized), and spent more time in bed during the night than those without apathy. Sleep latency, nMMA and TST did not differ significantly between the two subgroups. To our knowledge, this study is the first to identify a relationship between apathy and sleep disturbance in those with mild or moderate AD: apathy was associated with increased TIB during the night and more WASO. These results suggest that AD patients with apathy have less consolidated nocturnal sleep than those without apathy.

  View details for DOI 10.3233/JAD-2011-101701

  View details for Web of Science ID 000293377700009

  View details for PubMedID 21335662

• Effects of sleep on the cardiovascular and thermoregulatory systems: a possible role for hypocretins JOURNAL OF APPLIED PHYSIOLOGY Schwimmer, H., Stauss, H. M., Abboud, F., Nishino, S., Mignot, E., Zeitzer, J. M. 2010; 109 (4): 1053-1063

  Abstract

  Sleep influences the cardiovascular, endocrine, and thermoregulatory systems. Each of these systems may be affected by the activity of hypocretin (orexin)-producing neurons, which are involved in the etiology of narcolepsy. We examined sleep in male rats, either hypocretin neuron-ablated orexin/ataxin-3 transgenic (narcoleptic) rats or their wild-type littermates. We simultaneously monitored electroencephalographic and electromyographic activity, core body temperature, tail temperature, blood pressure, electrocardiographic activity, and locomotion. We analyzed the daily patterns of these variables, parsing sleep and circadian components and changes between states of sleep. We also analyzed the baroreceptor reflex. Our results show that while core temperature and heart rate are affected by both sleep and time of day, blood pressure is mostly affected by sleep. As expected, we found that both blood pressure and heart rate were acutely affected by sleep state transitions in both genotypes. Interestingly, hypocretin neuron-ablated rats have significantly lower systolic and diastolic blood pressure during all sleep stages (non-rapid eye movement, rapid eye movement) and while awake (quiet, active). Thus, while hypocretins are critical for the normal temporal structure of sleep and wakefulness, they also appear to be important in regulating baseline blood pressure and possibly in modulating the effects of sleep on blood pressure.

  View details for DOI 10.1152/japplphysiol.00516.2010

  View details for Web of Science ID 000285344900016

  View details for PubMedID 20705949

• Sex Differences in Phase Angle of Entrainment and Melatonin Amplitude in Humans JOURNAL OF BIOLOGICAL RHYTHMS Cain, S. W., Dennison, C. F., Zeitzer, J. M., Guzik, A. M., Khalsa, S. B., Santhi, N., Schoen, M. W., Czeisler, C. A., Duffy, J. F. 2010; 25 (4): 288-296

  Abstract

  Studies of sex differences in the timing of human circadian rhythms have reported conflicting results. This may be because the studies conducted to date have not controlled for the masking effects of the rest activity cycle on the circadian rhythms being assessed. In the present analysis of data collected under controlled conditions, we examined sex differences in the timing of circadian rhythms while minimizing masking from behavioral and environmental factors using a constant routine (CR) protocol. All participants (28 women and 28 men paired by habitual wake time; age range, 18 30 years) maintained a regular self selected sleep wake schedule at home prior to the study. After 3 baseline days in the laboratory, participants began a CR. Women were found to have a significantly higher melatonin amplitude and lower temperature amplitude than men. While sleep timing was the same between the 2 groups, the timing of the circadian rhythms of core body temperature and pineal melatonin secretion was earlier relative to sleep time in women as compared to men. Sleep therefore occurred at a later biological time for women than men, despite being at the same clock time. Given that sleep propensity and structure vary with circadian phase and are impacted by circulating melatonin, these findings may have important implications for understanding sex differences in sleep timing and duration, diurnal preference, and the prevalence of sleep disorders such as insomnia.

  View details for DOI 10.1177/0748730410374943

  View details for Web of Science ID 000280610000006

  View details for PubMedID 20679498

• Preliminary evidence that plasma oxytocin levels are elevated in major depression PSYCHIATRY RESEARCH Parker, K. J., Kenna, H. A., Zeitzer, J. M., Keller, J., Blasey, C. M., Amico, J. A., Schatzberg, A. F. 2010; 178 (2): 359-362

  Abstract

  It is well established that the neuropeptide oxytocin (OT) is involved in regulating social behavior, anxiety, and hypothalamic-pituitary-adrenal (HPA) axis physiology in mammals. Because individuals with major depression often exhibit functional irregularities in these measures, we test in this pilot study whether depressed subjects (n=11) exhibit dysregulated OT biology compared to healthy control subjects (n=19). Subjects were hospitalized overnight and blood samples were collected hourly between 1800 and 0900h. Plasma levels of OT, the closely related neuropeptide argine-vasopressin (AVP), and cortisol were quantified. Results indicated that depressed subjects exhibit increased OT levels compared to healthy control subjects, and this difference is most apparent during the nocturnal peak. No depression-related differences in AVP or cortisol levels were discerned. This depression-related elevation in plasma OT levels is consistent with reports of increased hypothalamic OT-expressing neurons and OT mRNA in depressed patients. This present finding is likewise consistent with the hypothesis that dysregulated OT biology may be a biomarker of the emotional distress and impaired social relationships which characterize major depression. Additional research is required to elucidate the role of OT in the pathophysiology of this psychiatric disorder.

  View details for DOI 10.1016/j.psychres.2009.09.017

  View details for Web of Science ID 000279988900025

  View details for PubMedID 20494448

  View details for PubMedCentralID PMC2902664

• Non-pharmacologic management of sleep disturbance in Alzheimer's disease JOURNAL OF NUTRITION HEALTH & AGING David, R., Zeitzer, J., Friedman, L., Noda, A., O'Hara, R., Robert, P., Yesavage, J. A. 2010; 14 (3): 203-206

  Abstract

  Sleep and wake in Alzheimer's disease (AD) are often fragmented as manifested by bouts of wakefulness at night and napping during the day. Management of sleep disturbances in AD is important because of their negative impact on both patients and caregivers. Pharmacological treatments, mainly sedative-hypnotics and antipsychotics, are often used but can be associated with significant adverse effects. Non-pharmacological treatments represent a beneficial alternative approach to the management of sleep disturbances in AD since they are associated with fewer adverse effects and their efficacy can be sustained after treatment has been completed. The aim of this article is to review non-pharmacological treatments, such as sleep hygiene, sleep restriction therapy (SRT), cognitive behavioral therapy (CBT), light therapy, and continuous positive airway pressure (CPAP), for the management of sleep/wake disturbances in AD.

  View details for DOI 10.1007/s12603-010-0050-9

  View details for Web of Science ID 000276527000006

  View details for PubMedID 20191254

• Role of Healthy Sleep Practices: Alcohol/Caffeine/Exercise/Scheduling INSOMNIA: DIAGNOSIS AND TREATMENT Friedman, L., Zeitzer, J. M., Mumenthaler, M. S., Sateia, M. J., Buysse, D. J. 2010: 260-267

  View details for Web of Science ID 000356054900024

• EXPOSURE TO BRIGHT, MILLISECOND LIGHT FLASHES ENHANCE OBJECTIVE MEASURES OF NOCTURNAL ALERTNESS IN HUMANS Zeitzer, J., Fisicaro, R., Ruby, N. F., Heller, H. OXFORD UNIV PRESS INC. 2010: A90

  View details for Web of Science ID 000208208000260

• INCIDENTAL IMPROVEMENT OF DEPRESSION IN CAREGIVERS DURING NON-PHARMACOLOGIC TREATMENT OF SLEEP DISRUPTION IN INDIVIDUALS WITH MEMORY IMPAIRMENT Friedman, L. F., Mather, C., Spira, A. P., Hernandez, B., Kim, E., Wicks, D., Sheikh, J., Yesavage, J. A., Zeitzer, J. OXFORD UNIV PRESS INC. 2010: A353

  View details for Web of Science ID 000208208001541

• Modafinil and gamma-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep BEHAVIOURAL PHARMACOLOGY Zeitzer, J. M., Buckmaster, C. L., Landoltd, H., Lyons, D. M., Mignot, E. 2009; 20 (7): 643-652

  Abstract

  Hypocretin-1 is a hypothalamic neuropeptide that is important in the regulation of wake and the lack of which results in the sleep disorder narcolepsy. Using a monkey that has consolidated wake akin to humans, we examined pharmacological manipulation of sleep and wake and its effects on hypocretin physiology. Monkeys were given the sleep-inducing γ-hydroxybutyrate (GHB) and the wake-inducing modafinil both in the morning and in the evening. Cerebrospinal fluid hypocretin-1 concentrations changed significantly in response to the drugs only when accompanied by a behavioral change (GHB-induced sleep in the morning or modafinil-induced wake in the evening). We also found that there was a large (180-fold) interindividual variation in GHB pharmacokinetics that explains variability in sleep induction in response to the drug. Our data indicate that the neurochemical concomitants of sleep and wake are capable of changing the physiological output of hypocretin neurons. Sleep independent of circadian timing is capable of decreasing cerebrospinal fluid hypocretin-1 concentrations. Furthermore, hypocretin neurons do not seem to respond to an 'effort' to remain awake, but rather keep track of time spent awake as a wake-promoting counterbalance to extended wakefulness.

  View details for DOI 10.1097/FBP.0b013e328331b9db

  View details for Web of Science ID 000270483300010

  View details for PubMedID 19752724

  View details for PubMedCentralID PMC2939929

• Elevated Anti-Streptococcal Antibodies in Patients with Recent Narcolepsy Onset SLEEP Aran, A., Lin, L., Nevsimalova, S., Plazzi, G., Hong, S. C., Weiner, K., Zeitzer, J., Mignot, E. 2009; 32 (8): 979-983

  Abstract

  Narcolepsy-cataplexy has long been thought to have an autoimmune origin. Although susceptibility to narcolepsy, like many autoimmune conditions, is largely genetically determined, environmental factors are involved based on the high discordance rate (approximately 75%) of monozygotic twins. This study evaluated whether Streptococcus pyogenes and Helicobacter pylori infections are triggers for narcolepsy.Retrospective, case-control.Sleep centers of general hospitals.200 patients with narcolepsy/hypocretin deficiency, with a primary focus on recent onset cases and 200 age-matched healthy controls. All patients were DQB1*0602 positive with low CSF hypocretin-1 or had clear-cut cataplexy.Participants were tested for markers of immune response to beta hemolytic streptococcus (anti-streptolysin O [ASO]; anti DNAse B [ADB]) and Helicobacter pylori [Anti Hp IgG], two bacterial infections known to trigger autoimmunity. A general inflammatory marker, C-reactive protein (CRP), was also studied. When compared to controls, ASO and ADB titers were highest close to narcolepsy onset, and decreased with disease duration. For example, ASO > or = 200 IU (ADB > or = 480 IU) were found in 51% (45%) of 67 patients within 3 years of onset, compared to 19% (17%) of 67 age matched controls (OR = 4.3 [OR = 4.1], P < 0.0005) or 20% (15%) of 69 patients with long-standing disease (OR = 4.0 [OR = 4.8], P < 0.0005]. CRP (mean values) and Anti Hp IgG (% positive) did not differ from controls.Streptococcal infections are probably a significant environmental trigger for narcolepsy.

  View details for Web of Science ID 000268557600004

  View details for PubMedID 19725248

• The effects of sleep on the cardiovascular and the thermoregulatory systems - possible role for hypocretin Schwimmer, H., Zeitzer, J. M., Yanagisawa, M., Nishino, S., Stauss, H. M., Abboud, F. M., Mignot, E. FEDERATION AMER SOC EXP BIOL. 2009

  View details for Web of Science ID 000208621505350

• Scheduled Bright Light for Treatment of Insomnia in Older Adults JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Friedman, L., Zeitzer, J. M., Kushida, C., Zhdanova, I., Noda, A., Lee, T., Schneider, B., Guilleminault, C., Sheikh, J., Yesavage, J. A. 2009; 57 (3): 441-452

  Abstract

  To determine whether bright light can improve sleep in older individuals with insomnia.Single-blind, placebo-controlled, 12-week, parallel-group randomized design comparing four treatment groups representing a factorial combination of two lighting conditions and two times of light administration.At-home light treatment; eight office therapy sessions.Thirty-six women and fifteen men (aged 63.6+/-7.1) meeting primary insomnia criteria recruited from the community.A 12-week program of sleep hygiene and exposure to bright ( approximately 4,000 lux) or dim light ( approximately 65 lux) scheduled daily in the morning or evening for 45 minutes.Within-group changes were observed for subjective (sleep logs, questionnaires) and objective (actigraphy, polysomnography) sleep measures after morning or evening bright light.Within-group changes for subjective sleep measures after morning or evening bright light were not significantly different from those observed after exposure to scheduled dim light. Objective sleep changes (actigraphy, polysomnography) after treatment were not significantly different between the bright and dim light groups. Scheduled light exposure was able to shift the circadian phase predictably but was unrelated to changes in objective or subjective sleep measures. A polymorphism in CLOCK predicted morningness but did not moderate the effects of light on sleep. The phase angle between the circadian system (melatonin midpoint) and sleep (darkness) predicted the magnitude of phase delays, but not phase advances, engendered by bright light.Except for one subjective measure, scheduled morning or evening bright light effects were not different from those of scheduled dim light. Thus, support was not found for bright light treatment of older individuals with primary insomnia.

  View details for DOI 10.1111/j.1532-5415.2008.02164.x

  View details for PubMedID 19187411

• Sleep apnea, apolipoprotein epsilon 4 allele, and TBI: Mechanism for cognitive dysfunction and development of dementia JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT O'Hara, R., Luzon, A., Hubbard, J., Zeitzer, J. M. 2009; 46 (6): 837-850

  Abstract

  Sleep apnea is prevalent among patients with traumatic brain injuries (TBIs), and initial studies suggest it is associated with cognitive impairments in these patients. Recent studies found that the apolipoprotein epsilon 4 (APOE epsilon 4) allele increases the risk for sleep disordered breathing, particularly sleep apnea. The APOE epsilon 4 allele is associated with cognitive decline and the development of dementia in the general population as well as in patients with TBI. These findings raise the question of whether patients with TBI who are APOE epsilon 4 allele carriers are more vulnerable to the negative effects of sleep apnea on their cognitive functioning. While few treatments are available for cognitive impairment, highly effective treatments are available for sleep apnea. Here we review these different lines of evidence, making a case that the interactive effects of sleep apnea and the APOE epsilon 4 allele represent an important mechanism by which patients with TBI may develop a range of cognitive and neurobehavioral impairments. Increased understanding of the relationships among sleep apnea, the APOE epsilon 4 allele, and cognition could improve our ability to ameliorate one significant source of cognitive impairment and risk for dementia associated with TBI.

  View details for DOI 10.1682/JRRD.2008.10.0140

  View details for Web of Science ID 000272638100015

  View details for PubMedID 20104407

• ASSOCIATION BETWEEN NIGHTTIME SLEEP AND DAYTIME ACTIVITY IN MEMORY-IMPAIRED INDIVIDUALS AND THEIR CAREGIVERS Friedman, L., Spira, A., Noda, A., Hernandez, B., Kim, E., Wicks, D., Sheikh, J., Yesavage, J., Zeitzer, J. M. OXFORD UNIV PRESS INC. 2009: A120

  View details for Web of Science ID 000265542000364

• HLA DQB1*0602 IS ASSOCIATED WITH SLEEP PERCEPTION IN OLDER INDIVIDUALS WITH INSOMNIA 23rd Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) Zeitzer, J., Grove, M. E., Mignot, E., Yesavage, J. A., Friedman, L. AMER ACAD SLEEP MEDICINE. 2009: A262–A262

  View details for Web of Science ID 000265542001152

• Neuropsychiatric diagnosis and management of chronic sequelae of war-related mild to moderate traumatic brain injury JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Halbauer, J. D., Ashford, J. W., Zeitzer, J. M., Adamson, M. M., Lew, H. L., Yesavage, J. A. 2009; 46 (6): 757-795

  Abstract

  Soldiers with a traumatic brain injury (TBI) present with an array of neuropsychiatric symptoms that can be grouped into nosological clusters: (1) cognitive dysfunctions: difficulties in memory, attention, language, visuospatial cognition, sensory-motor integration, affect recognition, and/or executive function typically associated with neocortical damage; (2) neurobehavioral disorders: mood, affect, anxiety, posttraumatic stress, and psychosis, as well as agitation, sleep problems, and libido loss, that may have been caused by damage to the cortex, limbic system, and/or brain stem monoaminergic projection systems; (3) somatosensory disruptions: impaired smell, vision, hearing, equilibrium, taste, and somatosensory perception frequently caused by trauma to the sensory organs or their projections through the brain stem to central processing systems; (4) somatic symptoms: headache and chronic pain; and (5) substance dependence. TBI-related cognitive impairment is common in veterans who have served in recent conflicts in the Middle East and is often related to blasts from improvised explosive devices. Although neurobehavioral disorders such as depression and posttraumatic stress disorder commonly occur after combat, the presentation of such disorders in those with head injury may pass undetected with use of current diagnostic criteria and neuropsychological instruments. With a multidimensional approach (such as the biopsychosocial model) applied to each symptom cluster, psychological, occupational, and social dysfunction can be delineated and managed.

  View details for DOI 10.1682/JRRD.2008.08.0119

  View details for Web of Science ID 000272638100010

  View details for PubMedID 20104402

• Insomnia in the context of traumatic brain injury JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT Zeitzer, J. M., Friedman, L., O'Hara, R. 2009; 46 (6): 827-835

  Abstract

  Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in the United States. One of the most common comorbidities of TBI is the disruption of normal sleep. While often viewed as a nuisance symptom, sleep disruption can delay TBI recovery and negatively affect many of the psychological (e.g., anxiety, depression) and neuromuscular (e.g., pain) sequelae of TBI, decreasing quality of life. Treatment of sleep disruption in the context of TBI is complicated by issues of an altered neuronal milieu, polypharmacy, and the complex relationship between the various comorbidities often found in patients with TBI. Given the growing number of veterans returning from combat with TBI and the elevated risk of comorbid disrupted sleep, both caused by and independent of TBI, a comprehensive review of sleep disruption and its treatment is of great relevance to the Department of Veterans Affairs.

  View details for DOI 10.1682/JRRD.2008.08.0099

  View details for Web of Science ID 000272638100014

  View details for PubMedID 20104406

• Vagal regulation, cortisol, and sleep disruption in women with metastatic breast cancer. Journal of clinical sleep medicine Palesh, O., Zeitzer, J. M., Conrad, A., Giese-Davis, J., Mustian, K. M., Popek, V., Nga, K., Spiegel, D. 2008; 4 (5): 441-449

  Abstract

  To determine the relationship between hypothalamic pituitary axis (HPA) dysregulation, vagal functioning, and sleep problems in women with metastatic breast cancer.Sleep was assessed by means of questionnaires and wrist actigraphy for 3 consecutive nights. The ambulatory, diurnal variation in salivary cortisol levels was measured at 5 time points over 2 days. Vagal regulation was assessed via respiratory sinus arrhythmia (RSA(TF)) during the Trier Social Stress Task.Ninety-nine women (54.6 +/- 9.62 years) with metastatic breast cancer.Longer nocturnal wake episodes (r = 0.21, p = 0.04, N=91) were associated with a flatter diurnal cortisol slope. Sleep disruption was also associated with diminished RSA(TF). Higher RSA baseline scores were significantly correlated with higher sleep efficiency (r = 0.39, p = 0.001, N=68) and correspondingly lower levels of interrupted sleep (waking after sleep onset, WASO; r = -0.38, p = 0.002, N=68), lower average length of nocturnal wake episodes (r = -0.43, p < 0.001, N=68), and a lower self-reported number of hours of sleep during a typical night (r = -0.27, p = 0.02, N=72). Higher RSA AUC was significantly related to higher sleep efficiency (r = 0.45, p < 0.001, N=64), and a correspondingly lower number of wake episodes (r = -0.27, p = 0.04, N=64), lower WASO (r = -0.40, p = 0.001, N=64), and with lower average length of nocturnal wake episodes (r = -0.41, p = 0.001, N=64). While demographics, disease severity, and psychological variables all explained some portion of the development of sleep disruption, 4 of the 6 sleep parameters examined (sleep efficiency, WASO, mean number of waking episodes, average length of waking episode) were best explained by RSA.These data provide preliminary evidence for an association between disrupted nocturnal sleep and reduced RSA the subsequent day, confirming an association between disrupted nocturnal sleep and flattened diurnal cortisol rhythm in women with metastatic breast cancer. They suggest that the stress-buffering effects of sleep may be associated with improved parasympathetic tone and normalized cortisol patterns during the day.

  View details for PubMedID 18853702

• Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial (vol 7, pg 136, 20008) LANCET NEUROLOGY Hughes, R. C., Donofrio, P., Bril, Bourgin, P., Zeitzer, J. M., Mignot, E., Chin, R. M., Neville, B. R., Peckham, C., Wade, A., Bedford, H., Scott, R. C., ICE Study Grp 2008; 7 (9): 771

  View details for DOI 10.1016/S1474-4422(08)70180-7

  View details for Web of Science ID 000258988400010

• CSF hypocretin-1 assessment in sleep and neurological disorders LANCET NEUROLOGY Bourgin, P., Zeitzer, J. M., Mignot, E. 2008; 7 (7): 649-662

  Abstract

  Concentrations of CSF hypocretin-1 (formerly orexin A) have been measured in many patients with sleep or neurological conditions. Low CSF hypocretin-1 is most predictive of narcolepsy in patients positive for HLA allele DQB1*0602, most of whom have cataplexy. By contrast, the diagnostic significance of low CSF hypocretin-1 is unclear in the presence of acute CNS inflammation or trauma. The clinical usefulness of CSF testing in hypersomnia that is symptomatic of a neurological disorder remains to be evaluated. Determination of CSF hypocretin-1 concentration to diagnose narcolepsy might be most useful in ambulatory patients with cataplexy but with a normal multiple sleep latency test (MSLT) result, or if MSLT is not interpretable, conclusive, or feasible. Because 98% of patients with hypocretin-1 deficiency are positive for HLA DQB1*0602, we suggest that HLA typing is a useful screen before lumbar puncture. Although hypocretin-1 deficiency in narcolepsy might have therapeutic relevance, additional research is needed in this area.

  View details for Web of Science ID 000257213600021

  View details for PubMedID 18565458

• Kleine-Levin syndrome: A systematic study of 108 patients ANNALS OF NEUROLOGY Arnulf, I., Lin, L., Gadoth, N., File, J., Lecendreux, M., Franco, P., Zeitzer, J., Lo, B., Faraco, J. H., Mignot, E. 2008; 63 (4): 482-493

  Abstract

  Kleine-Levin syndrome is a rare disorder characterized by relapsing-remitting episodes of hypersomnia, cognitive disturbances, and behavioral disturbances, such as hyperphagia and hypersexuality.We collected detailed clinical data and blood samples on 108 patients, 79 parent pairs, and 108 matched control subjects. We measured biological markers and typed human leukocyte antigen genes DR and DQ.Novel predisposing factors were identified including increased birth and developmental problems (odds ratio, 6.5). Jewish heritage was overrepresented, and five multiplex families were identified. Human leukocyte antigen typing was unremarkable. Patients were 78% male (mean age at onset, 15.7 +/- 6.0 years), averaged 19 episodes of 13 days, and were incapacitated 8 months over 14 years. The disease course was longer in men, in patients with hypersexuality, and when onset was after age 20. During episodes, all patients had hypersomnia, cognitive impairment, and derealization; 66% had megaphagia; 53% reported hypersexuality (principally men); and 53% reported a depressed mood (predominantly women). Patients were remarkably similar to control subjects between episodes regarding sleep, mood, and eating attitude, but had increased body mass index. We found marginal efficacy for amantadine and mood stabilizers, but found no increased family history for neuropsychiatric disorders.The similarity of the clinical and demographic features across studies strongly suggests that Kleine-Levin syndrome is a genuine disease entity. Familial clustering and increased prevalence in the Jewish population support a role for a major genetic susceptibility factor. Considering the inefficacy of available treatments, we propose that disease management should primarily be supportive and educational.

  View details for DOI 10.1002/ana.21333

  View details for Web of Science ID 000255454400011

  View details for PubMedID 18438947

• Vagal Regulation, Cortisol, and Sleep Disruption in Women with Metastatic Breast Cancer JOURNAL OF CLINICAL SLEEP MEDICINE Palesh, O., Zeitzer, J. M., Conrad, A., Giese-Davis, J., Mustian, K. M., Popek, V., Nga, K., Spiegel, D. 2008; 4 (5): 441-449

  Abstract

  To determine the relationship between hypothalamic pituitary axis (HPA) dysregulation, vagal functioning, and sleep problems in women with metastatic breast cancer.Sleep was assessed by means of questionnaires and wrist actigraphy for 3 consecutive nights. The ambulatory, diurnal variation in salivary cortisol levels was measured at 5 time points over 2 days. Vagal regulation was assessed via respiratory sinus arrhythmia (RSA(TF)) during the Trier Social Stress Task.Ninety-nine women (54.6 +/- 9.62 years) with metastatic breast cancer.Longer nocturnal wake episodes (r = 0.21, p = 0.04, N=91) were associated with a flatter diurnal cortisol slope. Sleep disruption was also associated with diminished RSA(TF). Higher RSA baseline scores were significantly correlated with higher sleep efficiency (r = 0.39, p = 0.001, N=68) and correspondingly lower levels of interrupted sleep (waking after sleep onset, WASO; r = -0.38, p = 0.002, N=68), lower average length of nocturnal wake episodes (r = -0.43, p < 0.001, N=68), and a lower self-reported number of hours of sleep during a typical night (r = -0.27, p = 0.02, N=72). Higher RSA AUC was significantly related to higher sleep efficiency (r = 0.45, p < 0.001, N=64), and a correspondingly lower number of wake episodes (r = -0.27, p = 0.04, N=64), lower WASO (r = -0.40, p = 0.001, N=64), and with lower average length of nocturnal wake episodes (r = -0.41, p = 0.001, N=64). While demographics, disease severity, and psychological variables all explained some portion of the development of sleep disruption, 4 of the 6 sleep parameters examined (sleep efficiency, WASO, mean number of waking episodes, average length of waking episode) were best explained by RSA.These data provide preliminary evidence for an association between disrupted nocturnal sleep and reduced RSA the subsequent day, confirming an association between disrupted nocturnal sleep and flattened diurnal cortisol rhythm in women with metastatic breast cancer. They suggest that the stress-buffering effects of sleep may be associated with improved parasympathetic tone and normalized cortisol patterns during the day.

  View details for Web of Science ID 000209777100009

  View details for PubMedCentralID PMC2576311

• Hypocretin deficiency in narcolepsy with atypical or without cataplexy Lin, L., Zeitzer, J., Einen, M., Zhang, J., Morkovitz, J., Bourgin, P., Mignot, E., Hong, S., Plazzi, G., Nevsimalova, S. OXFORD UNIV PRESS INC. 2008: A222

  View details for Web of Science ID 000255419001107

• Genetic polymorphism in clock predicts timing of circadian light sensitivity in humans Zeitzer, J., Friedman, L., Zhdanova, P., Lin, L., Kushida, C., Yesavage, J. A. AMER ACAD SLEEP MEDICINE. 2008: A365

  View details for Web of Science ID 000255419001536

• Preliminary evidence that hippocampal volumes in monkeys predict stress levels of adrenocorticotropic hormone BIOLOGICAL PSYCHIATRY Lyons, D. M., Parker, K. J., Zeitzer, J. M., Buckmaster, C. L., Schatzberg, A. F. 2007; 62 (10): 1171-1174

  Abstract

  Hippocampal volumes previously determined in monkeys by magnetic resonance imaging are used to test the hypothesis that small hippocampi predict increased stress levels of adrenocorticotropic hormone (ACTH).Plasma ACTH levels were measured after restraint stress in 19 male monkeys pretreated with saline or hydrocortisone. Monkeys were then randomized to an undisturbed control condition or intermittent social separations followed by new pair formations. After 17 months of exposure to the intermittent social manipulations, restraint stress tests were repeated to determine test/retest correlations.Individual differences in postrestraint stress ACTH levels over the 17-month test/retest interval were remarkably consistent for the saline (r(s) = .82, p = .0004) and hydrocortisone (r(s) = .78, p = .001) pretreatments. Social manipulations did not affect postrestraint stress ACTH levels, but monkeys with smaller hippocampal volumes responded to restraint after saline pretreatment with greater increases in ACTH levels with total brain volume variation controlled as a statistical covariate (beta = -.58, p = .031). Monkeys with smaller hippocampal volumes also responded with diminished sensitivity to glucocorticoid feedback determined by greater postrestraint ACTH levels after pretreatment with hydrocortisone (beta = -.68, p = .010).These findings support clinical reports that small hippocampi may be a risk factor for impaired regulation of the hypothalamic-pituitary-adrenal axis in humans with stress-related psychiatric disorders.

  View details for DOI 10.1016/i.biopsych.2007.03.012

  View details for Web of Science ID 000250905800015

  View details for PubMedID 17573043

  View details for PubMedCentralID PMC2129091

• Plasma melatonin rhythms in young and older humans during sleep, sleep deprivation, and wake SLEEP Zeitzer, J. M., Duffy, J. F., Lockley, S. W., Dijk, D., Czeisler, C. A. 2007; 30 (11): 1437-1443

  Abstract

  To determine the effects of sleep and sleep deprivation on plasma melatonin concentrations in humans and whether these effects are age-dependent.At least 2 weeks of regular at-home, sleep/wake schedule followed by 3 baseline days in the laboratory and at least one constant routine (sleep deprivation).General Clinical Research Center (GCRC), Brigham and Women's Hospital, Boston, MA.In Study 1, one group (<10 lux when awake) of 19 young men (18-30 y) plus a second group (<2 lux when awake) of 15 young men (20-28 y) and 10 young women (19-27 y); in Study 2, 90 young men (18-30 y), 18 older women (65-81 y), and 11 older men (64-75 y). All participants were in good health, as determined by medical and psychological screening.One to three constant routines with interspersed inversion of the sleep/wake cycle in those with multiple constant routines.Examination of plasma melatonin concentrations and core body temperature. Study 1. There was a small, but significant effect of sleep deprivation of up to 50 hours on melatonin concentrations (increase of 9.81 +/- 3.73%, P <0.05, compared to normally timed melatonin). There was also an effect of circadian phase angle with the prior sleep episode, such that if melatonin onset occurred <8 hours after wake time, the amplitude was significantly lower (22.4% +/- 4.79%, P <0.001). Study 2. In comparing melatonin concentrations during sleep to the same hours during constant wakefulness, in young men, melatonin amplitude was 6.7% +/- 2.1% higher(P <0.001) during the sleep episode. In older men, melatonin amplitude was 37.0% +/- 12.5% lower (P <0.05) during the sleep episode and in older women, melatonin amplitude was non-significantly 10.9% +/- 8.38% lower (P = 0.13) during the sleep episode.Both sleep and sleep deprivation likely influence melatonin amplitude, and the effect of sleep on melatonin appears to be age dependent.

  View details for Web of Science ID 000250724600005

  View details for PubMedID 18041478

• Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Zeitzer, J. M., Buckmaster, C. L., Lyons, D. M., Mignot, E. 2007; 293 (4): R1736-R1742

  Abstract

  The neuropeptides hypocretins (orexins), the loss of which results in the sleep disorder narcolepsy, are hypothesized to be involved in the consolidation of wakefulness and have been proposed to be part of the circadian-driven alertness signal. To elucidate the role of hypocretins in the consolidation of human wakefulness we examined the effect of wake extension on hypocretin-1 in squirrel monkeys, primates that consolidate wakefulness during the daytime as do humans. Wake was extended up to 7 h with hypocretin-1, cortisol, ghrelin, leptin, locomotion, and feeding, all being assayed. Hypocretin-1 (P < 0.01), cortisol (P < 0.001), and locomotion (P < 0.005) all increased with sleep deprivation, while ghrelin (P = 0.79) and leptin (P = 1.00) did not change with sleep deprivation. Using cross-correlation and multivariate modeling of these potential covariates along with homeostatic pressure (a measure of time awake/asleep), we found that time of day and homeostatic pressure together explained 44% of the variance in the hypocretin-1 data (P < 0.001), while cortisol did not significantly contribute to the overall hypocretin-1 variance. Locomotion during the daytime, but not during the nighttime, helped explain < 5% of the hypocretin-1 variance (P < 0.05). These data are consistent with earlier evidence indicating that in the squirrel monkey hypocretin-1 is mainly regulated by circadian inputs and homeostatic sleep pressure. Concomitants of wakefulness that affect hypocretin-1 in polyphasic species, such as locomotion, food intake, and food deprivation, likely have a more minor role in monophasic species, such as humans.

  View details for DOI 10.1152/ajpregu.00460.2007

  View details for Web of Science ID 000250088000033

  View details for PubMedID 17686881

• A physiologically based mathematical model of melatonin including ocular light suppression and interactions with the circadian pacemaker JOURNAL OF PINEAL RESEARCH St Hilaire, M. A., Gronfier, C., Zeitzer, J. M., Klerman, E. B. 2007; 43 (3): 294-304

  Abstract

  The rhythm of plasma melatonin concentration is currently the most accurate marker of the endogenous human circadian pacemaker. A number of methods exist to estimate circadian phase and amplitude from the observed melatonin rhythm. However, almost all these methods are limited because they depend on the shape and amplitude of the melatonin pulse, which vary among individuals and can be affected by environmental influences, especially light. Furthermore, these methods are not based on the underlying known physiology of melatonin secretion and clearance, and therefore cannot accurately quantify changes in secretion and clearance observed under different experimental conditions. A published physiologically-based mathematical model of plasma melatonin can estimate synthesis onset and offset of melatonin under dim light conditions. We amended this model to include the known effect of melatonin suppression by ocular light exposure and to include a new compartment to model salivary melatonin concentration, which is widely used in clinical settings to determine circadian phase. This updated model has been incorporated into an existing mathematical model of the human circadian pacemaker and can be used to simulate experimental protocols under a number of conditions.

  View details for DOI 10.1111/j.1600-079X.2007.00477.x

  View details for Web of Science ID 000249425400012

  View details for PubMedID 17803528

  View details for PubMedCentralID PMC2714090

• Sleep/wake fragmentation disrupts metabolism in a mouse model of narcolepsy JOURNAL OF PHYSIOLOGY-LONDON Zhang, S., Zeitzer, J. M., Sakurai, T., Nishino, S., Mignot, E. 2007; 581 (2): 649-663

  Abstract

  Recent population studies have identified important interrelationships between sleep duration and body weight regulation. The hypothalamic hypocretin/orexin neuropeptide system is able to influence each of these. Disruption of the hypocretin system, such as occurs in narcolepsy, leads to a disruption of sleep and is often associated with increased body mass index. We examined the potential interrelationship between the hypocretin system, metabolism and sleep by measuring locomotion, feeding, drinking, body temperature, sleep/wake and energy metabolism in a mouse model of narcolepsy (ataxin-ablation of hypocretin-expressing neurons). We found that locomotion, feeding, drinking and energy expenditure were significantly reduced in the narcoleptic mice. These mice also exhibited severe sleep/wake fragmentation. Upon awakening, transgenic and control mice displayed a similar rate of increase in locomotion and food/water intake with time. A lack of long wake episodes partially or entirely explains observed differences in overall locomotion, feeding and drinking in these transgenic mice. Like other parameters, energy expenditure also rose and fell depending on the sleep/wake status. Unlike other parameters, however, energy expenditure in control mice increased upon awakening at a greater rate than in the narcoleptic mice. We conclude that the profound sleep/wake fragmentation is a leading cause of the reduced locomotion, feeding, drinking and energy expenditure in the narcoleptic mice under unperturbed conditions. We also identify an intrinsic role of the hypocretin system in energy expenditure that may not be dependent on sleep/wake regulation, locomotion, or food intake. This investigation illustrates the need for coordinated study of multiple phenotypes in mouse models with altered sleep/wake patterns.

  View details for DOI 10.1113/jphysiol.2007.129510

  View details for Web of Science ID 000246756000022

  View details for PubMedID 17379635

  View details for PubMedCentralID PMC2075199

• Decreased sensitivity to phase-delaying effects of moderate intensity light in older subjects NEUROBIOLOGY OF AGING Duffy, J. F., Zeitzer, J. M., Czeisler, C. A. 2007; 28 (5): 799-807

  Abstract

  Aging is associated with a change in the relationship between the timing of sleep and circadian rhythms, such that the rhythms occur later with respect to sleep than in younger adults. To investigate whether a difference in the phase-delaying response to evening light contributes to this, we conducted a 9-day inpatient study in 10 healthy older (> or =65 y.o.) subjects. We assessed circadian phase in a constant routine, exposed each subject to a 6.5h broad-spectrum light stimulus beginning in the early biological night, and reassessed circadian phase. The stimuli spanned a range from very dim (approximately 2 lx) to very bright (approximately 8000 lx) indoor light. We found a significant dose-response relationship between illuminance and the phase shift of the melatonin rhythm, with evidence that sensitivity, but not the maximal response to light, differed from that of younger adults. These findings suggest an age-related reduction in the phase-delaying response to moderate light levels. However, our findings alone do not explain the altered phase relationship between sleep and circadian rhythms associated with aging.

  View details for DOI 10.1016/j.neurobiolaging.2006.03.005

  View details for Web of Science ID 000245109700018

  View details for PubMedID 16621166

  View details for PubMedCentralID PMC1855248

• Normal cerebrospinal fluid levels of hypocretin-1 (orexin A) in patients with fibromyalgia syndrome SLEEP MEDICINE Taiwo, O. B., Russell, I. J., Mignot, E., Lin, L., Michalek, J. E., Haynes, W., Xiao, Y., Zeiter, J. M., Larson, A. A. 2007; 8 (3): 260-265

  Abstract

  The hypothalamic neuropeptide hypocretin (orexin) modulates sleep-wake, feeding and endocrine functions. Cerebrospinal fluid (CSF) hypocretin-1 (Hcrt-1) concentrations are low in patients with narcolepsy-cataplexy, a sleep disorder characterized by hypersomnolence and rapid eye movement (REM) sleep abnormalities.We determined CSF Hcrt-1 concentrations of patients with the fibromyalgia syndrome (FMS), a condition characterized by fatigue, insomnia and in some cases daytime hypersomnolence.Basal CSF levels of Hcrt-1 in FMS did not differ from those in healthy normal controls.These findings suggest that abnormally low Hcrt-1 is not a likely cause of fatigue in FMS.

  View details for DOI 10.1016/j.sleep.2006.08.015

  View details for Web of Science ID 000246343100010

  View details for PubMedID 17369087

• In Alzheimer disease, increased wake fragmentation found in those with lower hypocretin-1 NEUROLOGY Friedman, L. F., Zeitzer, J. M., Lin, L., Hoff, D., Mignot, E., Peskind, E. R., Yesavage, J. A. 2007; 68 (10): 793-794

  View details for Web of Science ID 000244679900020

  View details for PubMedID 17339595

• Hypocretin-1 is inversely associated with wake fragmentation in Alzheimer's disease 21st Annual Meeting of the American-Professional-Sleep-Societies Zeitzer, J., Friedman, L., Lin, L., Mignot, E., Peskind, E., Yesavage, J. AMER ACAD SLEEP MEDICINE. 2007: A302–A302

  View details for Web of Science ID 000246224900882

• Neurobiology of Narcolepsy and Hypersomnia NEUROBIOLOGY OF DISEASE Mignot, E., Zeitzer, J. M., Gilman, S. 2007: 715–22

  View details for DOI 10.1016/B978-012088592-3/50068-2

  View details for Web of Science ID 000310853000067

• Diurnal fluctuations of histamine and glutathione levels in the primate CSF Kodama, T., Zeitzer, J. M., Honda, Y., Buckmaster, C. L., Lyons, D. M., Mignot, E., Nishino, S. BLACKWELL PUBLISHING. 2006: 239

  View details for Web of Science ID 000239966000663

• The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions TRENDS IN PHARMACOLOGICAL SCIENCES Zeitzer, J. M., Nishin, S., Mignot, E. 2006; 27 (7): 368-374

  Abstract

  Narcolepsy is characterized by excessive daytime sleepiness, cataplexy and other manifestations of dissociated rapid eye movement sleep. Narcolepsy is typically treated with amphetamine-like stimulants (sleepiness) and antidepressants (cataplexy). Newer compounds, such as modafinil (non-amphetamine wake-promoting compound for excessive daytime sleepiness) and sodium oxybate (short-acting sedative for fragmented nighttime sleep, cataplexy, excessive daytime sleepiness), are increasingly used. Recent discoveries indicate that the major pathophysiology of human narcolepsy is the loss of lateral hypothalamic neurons that produce the neuropeptide hypocretin (orexin). Approximately 90% of people diagnosed as having narcolepsy with cataplexy are hypocretin ligand deficient. This has led to the development of new diagnostic tests (cerebrospinal fluid hypocretin-1 measurements). Hypocretin receptor agonists are likely to be ideal therapeutic options for hypocretin-deficient narcolepsy but such compounds are still not available in humans.

  View details for DOI 10.1016/j.tips.2006.05.006

  View details for Web of Science ID 000239368900005

  View details for PubMedID 16766052

• Extracellular adenosine in the human brain during sleep and sleep deprivation: An in vivo microdialysis study SLEEP Zeitzer, J. M., Morales-Villagran, A., Maidment, N. T., Behnke, E. J., Ackerson, L. C., Lopez-Rodriguez, F., Fried, I., Engel, J., Wilson, C. L. 2006; 29 (4): 455-461

  Abstract

  To examine the pattern of extracellular adenosine in the human brain during sleep deprivation, sleep, and normal wake.Following recovery from implantation of clinical depth electrodes, epilepsy patients remained awake for 40 continuous hours, followed by a recovery sleep episode.Neurology ward at UCLA Medical Center.Seven male epilepsy patients undergoing depth electrode localization of pharmacologically refractory seizures.All subjects were implanted with depth electrodes, a subset of which were customized to contain microdialysis probes. Microdialysis samples were collected during normal sleep, sleep deprivation, and recovery sleep from human amygdalae (n = 8), hippocampus (n = 1), and cortex (n = 1).In none of the probes did we observe an increase in extracellular adenosine during the sleep deprivation. There was a significant, though very small, diurnal oscillation (2.5%) in 5 of the 8 amygdalae. There was no effect of epileptogenicity on the pattern of extracellular adenosine.Our observations, along with those in animal studies, indicate that the role of extracellular adenosine in regulating sleep pressure is not a global brain phenomenon but is likely limited to specific basal forebrain areas. Thus, if energy homeostasis is a function of sleep, an increased rate of adenosine release into the extracellular milieu of the amygdala, cortex, or hippocampus is unlikely to be a marker of such a process.

  View details for Web of Science ID 000237061300009

  View details for PubMedID 16676778

• Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion SPINAL CORD Scheer, F. A., Zeitzer, J. M., Ayas, N. T., Brown, R., Czeisler, C. A., Shea, S. A. 2006; 44 (2): 78-81

  Abstract

  Case-controlled preliminary observational study.Melatonin is usually secreted only at night and may influence sleep. We previously found that complete cervical spinal cord injury (SCI) interrupts the neural pathway required for melatonin secretion. Thus, we investigated whether the absence of night time melatonin in cervical SCI leads to sleep disturbances.General Clinical Research Center, Brigham and Women's Hospital, Boston, USA.In an ancillary analysis of data collected in a prior study, we assessed the sleep patterns of three subjects with cervical SCI plus absence of nocturnal melatonin (SCI levels: C4A, C6A, C6/7A) and two control patients with thoracic SCI plus normal melatonin rhythms (SCI levels: T4A, T5A). We also compared those results to the sleep patterns of 10 healthy control subjects.The subjects with cervical SCI had significantly lower sleep efficiency (median 83%) than the control subjects with thoracic SCI (93%). The sleep efficiency of subjects with thoracic SCI was not different from that of healthy control subjects (94%). There was no difference in the proportion of the different sleep stages, although there was a significantly increased REM-onset latency in subjects with cervical SCI (220 min) as compared to subjects with thoracic SCI (34 min). The diminished sleep in cervical SCI was not associated with sleep apnea or medication use.We found that cervical SCI is associated with decreased sleep quality. A larger study is required to confirm these findings. If confirmed, the absence of night time melatonin in cervical SCI may help explain their sleep disturbances, raising the possibility that melatonin replacement therapy could help normalize sleep in this group.

  View details for DOI 10.1038/sj.sc.3101784

  View details for Web of Science ID 000235068600002

  View details for PubMedID 16130027

  View details for PubMedCentralID PMC2882209

• Hypocretin/orexin effects on cardiovascular regulation during sleep schwimmer H.,,, Zeitzer, J. M., Masashi, Y., Nishino, S., Shengwen, Z., Mignot, E. OXFORD UNIV PRESS INC. 2006: A31

  View details for Web of Science ID 000237916700096

• Modeling the effects of homeostatic drive, circadian time, locomotor activity, and HPA axis activation on hypocretin-1 (orexin A) concentrations in the squirrel monkey Zeitzer, J., Buckmaster, C. L., Lyons, D. M., Mignot, E. OXFORD UNIV PRESS INC. 2006: A10

  View details for Web of Science ID 000237916700031

• Kleine-Levin syndrome: a systematic review of 186 cases in the literature BRAIN Arnulf, I., Zeitzer, J. M., File, J., Farber, N., Mignot, E. 2005; 128: 2763-2776

  Abstract

  Kleine-Levin syndrome (KLS) is a rare disorder with symptoms that include periodic hypersomnia, cognitive and behavioural disturbances. Large series of patients are lacking. In order to report on various KLS symptoms, identify risk factors and analyse treatment response, we performed a systematic review of 195 articles, written in English and non-English languages, which are available on Medline dating from 1962 to 2004. Doubtful or duplicate cases, case series without individual details and reviews (n = 56 articles) were excluded. In addition, the details of 186 patients from 139 articles were compiled. Primary KLS cases (n = 168) were found mostly in men (68%) and occurred sporadically worldwide. The median age of onset was 15 years (range 4-82 years, 81% during the second decade) and the syndrome lasted 8 years, with seven episodes of 10 days, recurring every 3.5 months (median values) with the disease lasting longer in women and in patients with less frequent episodes during the first year. It was precipitated most frequently by infections (38.2%), head trauma (9%), or alcohol consumption (5.4%). Common symptoms were hypersomnia (100%), cognitive changes (96%, including a specific feeling of derealization), eating disturbances (80%), hypersexuality (43%), compulsions (29%), and depressed mood (48%). In 75 treated patients (213 trials), somnolence decreased using stimulants (mainly amphetamines) in 40% of cases, while neuroleptics and antidepressants were of poor benefit. Only lithium (but not carbamazepine or other antiepileptics) had a higher reported response rate (41%) for stopping relapses when compared to medical abstention (19%). Secondary KLS (n = 18) patients were older and had more frequent and longer episodes, but had clinical symptoms and treatment responses similar to primary cases. In conclusion, KLS is a unique disease which may be more severe in female and secondary cases.

  View details for DOI 10.1093/brain/awh620

  View details for Web of Science ID 000233667500004

  View details for PubMedID 16230322

• Temporal dynamics of late-night photic stimulation of the human circadian timing system AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Zeitzer, J. M., Khalsa, S. B., Boivin, D. B., Duffy, J. F., Shanahan, T. L., Kronauer, R. E., Czeisler, C. A. 2005; 289 (3): R839-R844

  Abstract

  The light-dark cycle is the primary synchronizing factor that keeps the internal circadian pacemaker appropriately aligned with the environmental 24-h day. Although it is known that ocular light exposure can effectively shift the human circadian pacemaker and do so in an intensity-dependent manner, the curve that describes the relationship between light intensity and pacemaker response has not been fully characterized for light exposure in the late biological night. We exposed subjects to 3 consecutive days of 5 h of experimental light, centered 1.5 h after the timing of the fitted minimum of core body temperature, and show that such light can phase advance shift the human circadian pacemaker in an intensity-dependent manner, with a logistic model best describing the relationship between light intensity and phase shift. A similar sigmoidal relationship is also observed between light intensity and the suppression of plasma melatonin concentrations that occurs during the experimental light exposure. As with a simpler, 1-day light exposure during the early biological night, our data indicate that the human circadian pacemaker is highly sensitive even to typical room light intensities during the late biological night, with approximately 100 lux evoking half of the effects observed with light 10 times as bright.

  View details for DOI 10.1152/ajpregu.00232.2005

  View details for Web of Science ID 000231243700026

  View details for PubMedID 15890792

• Bilateral oculosympathetic paresis associated with loss of nocturnal melatonin secretion in patients with spinal cord injury JOURNAL OF SPINAL CORD MEDICINE Zeitzer, J. M., Ayas, N. T., Wu, A. D., Czeisler, C. A., Brown, R. 2005; 28 (1): 55-59

  Abstract

  Lesions along the sympathetic pathway to the eye produce oculosympathetic paresis (OSP, Horner's syndrome). The oculosympathetic pathway descends from the hypothalamus through the cervical spinal cord and ascends to the superior cervical ganglion (SCG), which innervates sympathetic targets in the ipsilateral face and eye. This pathway appears to closely co-localize with a similar retino-pineal neural pathway from the hypothalamus through the cervical spinal cord and SCG to the pineal gland. As such, lesions along this shared pathway, such as occur in neurologically complete injury to the cervical spinal cord (tetraplegia), would be predicted to result in simultaneous OSP and loss of pineal melatonin production. Loss of melatonin production may contribute to the pervasive sleep disruption observed in patients with tetraplegia.We assessed the presence of OSP by photographic documentation of ptosis and pupillary dilation response to cocaine eye drops in 5 individuals with neurologically complete damage to their upper thoracic or lower cervical spinal cord. We correlated these results with an analysis of the pattern of melatonin production in these same individuals.Bilateral OSP was present in individuals with cervical spinal cord injury; each also lacked significant production of melatonin. No evidence of OSP was observed in the 2 individuals with thoracic spinal cord injury below the level of the oculosympathetic pathway. Both had normal circadian rhythms of melatonin production, with timing and amplitude of the rhythm within normal parameters.The presence of bilateral oculosympathetic paresis can be predictive of the complete loss of the nocturnal production of melatonin.

  View details for Web of Science ID 000234835600012

  View details for PubMedID 15832904

• Reduced sleep efficiency in cervical spinal cord injury; Association with abolished nighttime melatonin secretion Scheer, F. A., Zeitzer, J. M., Ayas, N. T., Brown, R., Czeisler, C. A., Shea, S. A. OXFORD UNIV PRESS INC. 2005: A68

  View details for Web of Science ID 000228906100203

• Sleep-deprivation dose response effects on hypocretin-1 (orexin A) concentrations in a diurnal, sleep consolidating primate, the squirrel monkey Zeitzer, J., Buckmaster, C. L., Lyons, D. M., Mignot, E. OXFORD UNIV PRESS INC. 2005: A142

  View details for Web of Science ID 000228906100420

• Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release SLEEP Zhang, S. W., Zeitzer, J. M., Yoshida, Y., Wisor, J. P., Nishino, S., Edgar, D. M., Mignot, E. 2004; 27 (4): 619-627

  Abstract

  Hypocretins (orexins) are involved in the sleep disorder narcolepsy. While hypocretin-1 has a daily oscillation, little is known regarding the relative contribution of circadian and homeostatic components on hypocretin release. The effect of lesions of the suprachiasmatic nucleus (SCN) on hypocretin-1 in the cerebrospinal fluid (CSF) was examined.SCN-ablated (SCNx) and sham-operated control rats were implanted with activity-temperature transmitters. Animals were housed individually under 1 of 3 lighting conditions: 12-hour:12-hour light:dark cycle (LD), constant light (LL), and constant darkness (DD). Lesions were verified histologically and shown not to affect hypocretin-containing cells. Hypocretin-1 concentrations in the CSF were determined every 4 hours using radioimmunoassays.Control animals displayed robust circadian (LL, DD) and diurnal (LD) fluctuations in CSF hypocretin-1, locomotor activity, and temperature. Peak CSF hypocretin-1 was at the end of the active period. Activity, temperature, and CSF hypocretin-1 were arrhythmic in SCNx animals in LL and DD. In LD, a weak but significant fluctuation in activity and temperature but not CSF hypocretin-1 was observed in SCNx animals. We also explored correlations between CSF hypocretin-1, CSF corticosterone, and locomotor activity occurring prior to CSF sampling in arrhythmic SCNx rats under constant conditions. Significant correlations between hypocretin-1 and activity were observed both across and within animals, suggesting that interindividual and time-of-the-day differences in activity have significant effects on hypocretin release in arrhythmic animals. No correlation was found between CSF hypocretin-1 and corticosterone.Hypocretin-1 release is under SCN control. Locomotor activity influences the activity of the hypocretin neurons.

  View details for Web of Science ID 000223169300007

  View details for PubMedID 15282996

• Locomotor-dependent and -independent components to hypocretin-1 (orexinA) regulation in sleep-wake consolidating monkeys JOURNAL OF PHYSIOLOGY-LONDON Zeitzer, J. M., Buckmaster, C. L., Lyons, D. M., Mignot, E. 2004; 557 (3): 1045-1053

  Abstract

  The hypocretin system is involved in the integration of hypothalamic functions with sleep and wake. Hypocretin-1 release peaks at the end of the active period in both diurnal and nocturnal species. A role for hypocretin-1 in the generation of locomotor activity has been suggested by electrophysiological and neurochemical studies in rodents, dogs and cats. These species, however, do not consolidate wake into a single, daily bout and manipulations of locomotion elicit changes in wakefulness, making it difficult to parse the relative contribution of these two factors. We have examined the relationship between locomotion and hypocretin-1 in a wake-consolidating animal, the squirrel monkey (Saimiri sciureus). Strikingly, we found that restricting locomotion to 17% of usual activity had no significant effect on the normal diurnal rise in cerebrospinal fluid (CSF) hypocretin-1, despite an associated increase in CSF cortisol. Increasing locomotion to greater than baseline activity did not significantly increase CSF hypocretin-1 concentrations, but did appear to have a positive modulatory effect on CSF hypocretin-1. In this wake-consolidating animal, locomotion is not necessary for CSF hypocretin-1 to increase throughout the daytime, but high levels of locomotion are likely to provide a small positive feedback onto the hypocretin system.

  View details for DOI 10.1113/jphysiol.2004.061606

  View details for Web of Science ID 000222403700029

  View details for PubMedID 15107479

  View details for PubMedCentralID PMC1665142

• Locomotor-dependent and -independent regulation of hypocretin-1 (Orexin A) in the squirrel monkey Zeitzer, J., Buckmaster, C. L., Lyons, D. M., Mignot, E. OXFORD UNIV PRESS INC. 2004: 25

  View details for Web of Science ID 000223169400058

• Effect of suprachiasmatic nucleus lesions on rat cerebrospinal fluid hypocretin-1 regulation Zhang, S., Zeitzer, J. M., Yoshida, Y., Wisor, J. P., Nishino, S., Edgar, D. M., Mignot, E. OXFORD UNIV PRESS INC. 2004: 1

  View details for Web of Science ID 000223169400004

• Diurnal variation of cerebrospinal fluid hypocretin-1 (orexin-A) levels in control and depressed subjects 16th Annual Meeting of the Associated-Professional-Sleep-Societies Salomon, R. M., Ripley, B., Kennedy, J. S., Johnson, B., Schmidt, D., Zeitzer, J. M., Nishino, S., Mignot, E. ELSEVIER SCIENCE INC. 2003: 96–104

  Abstract

  Hypocretins, excitatory neuropeptides at monoaminergic synapses, appear to regulate human sleep-wake cycles. Undetectable cerebrospinal fluid hypocretin-1 levels are seen in narcolepsy, which is frequently associated with secondary depression. Shortened rapid eye movement latency is observed in both narcolepsy and depression. Cerebrospinal fluid hypocretin-1 levels have not been reported in mood disorders.We examined hypocretin-1 levels in 14 control and 15 depressed subjects. Cerebrospinal fluid was drawn continuously in supine subjects for 24 hours with an indwelling intrathecal catheter under entrained light-dark conditions. Depressed subjects were studied before and after 5 weeks of sertraline (n=10, three nonresponders) or bupropion (n=5, two nonresponders).Hypocretin-1 levels varied slightly (amplitude 10%) but significantly across the diurnal cycle in control subjects, with amplitude significantly reduced in depression (3%). Levels were lowest at midday, surprising for a hypothetically wake-promoting peptide. Mean hypocretin levels trended higher in depressive than in control subjects. Hypocretin-1 levels decreased modestly but significantly after sertraline (-14%) but not bupropion.Our results are consistent with previous physiologic findings in depression indicating dampened diurnal variations in hypocretin-1. The finding that sertraline but not bupropion slightly decreased cerebrospinal fluid hypocretin-1 indicates a serotoninergic influence on hypocretin tone.

  View details for DOI 10.1016/S0006-3223(03)01740-7

  View details for Web of Science ID 000184213800002

  View details for PubMedID 12873798

• Hypocretin regulation in a primate model of human wake regulation Zeitzer, J. M., Buckmaster, C. L., Lyons, D. M., Mignot, E. AMER ACADEMY SLEEP MEDICINE. 2003: A23

  View details for Web of Science ID 000182841100057

• Circadian and homeostatic regulation of hypocretin in a primate model: Implications for the consolidation of wakefulness JOURNAL OF NEUROSCIENCE Zeitzer, J. M., Buckmaster, C. L., Parker, K. J., Hauck, C. M., Lyons, D. M., Mignot, E. 2003; 23 (8): 3555-3560

  Abstract

  In humans, consolidation of wakefulness into a single episode can be modeled as the interaction of two processes, a homeostatic "hour-glass" wake signal that declines throughout the daytime and a circadian wake-promoting signal that peaks in the evening. Hypocretins, novel hypothalamic neuropeptides that are dysfunctional in the sleep disorder narcolepsy, may be involved in the expression of the circadian wake-promoting signal. Hypocretins (orexins) are wake-promoting peptides, but their role in normal human sleep physiology has yet to be determined. We examined the daily temporal pattern of hypocretin-1 in the cisternal CSF of the squirrel monkey, a New World primate with a pattern of wake similar to that of humans. Hypocretin-1 levels peaked in the latter third of the day, consistent with the premise that hypocretin-1 is involved in wake regulation. When we lengthened the wake period by 4 hr, hypocretin-1 concentrations remained elevated, indicating a circadian-independent component to hypocretin-1 regulation. Changes in the stress hormone cortisol were not correlated with hypocretin-1 changes. Although hypocretin-1 is at least partially activated by a reactive homeostatic mechanism, it is likely also regulated by the circadian pacemaker. In the squirrel monkey, hypocretin-1 works in opposition to the accumulating sleep drive during the day to maintain a constant level of wake.

  View details for Web of Science ID 000182475200052

  View details for PubMedID 12716965

• Regional analyses of CNS microdialysate glucose and lactate in seizure patients EPILEPSIA Cornford, E. M., Shamsa, K., Zeitzer, J. M., Enriquez, C. M., Wilson, C. L., Behnke, E. J., Fried, I., Engel, J. 2002; 43 (11): 1360-1371

  Abstract

  To correlate glucose (and lactate) results obtained from microdialysate to recent studies suggesting that glucose transporter activity may be significantly altered in seizures.We used a fluorometric technique to quantify glucose and lactate levels in microdialysates collected from two to four depth electrodes implanted per patient in the temporal and frontal lobes of a series of four patients. Hour-by-hour and day-to-day changes in brain glucose and lactate levels at the same site were recorded. Additionally we compared regional variations in lactate/glucose ratios around the predicted epileptogenic region.Lactate/glucose ratios in the range of 1-2:1 were the most commonly seen. When the lactate/glucose ratio was <1:1, we typically observed a relative increase in local glucose concentration (rather than decreased lactate), suggesting increased transport, perhaps without increased glycolysis. In some sites, lactate/glucose ratios of 3:1-15:1 were seen, suggesting that a circumscribed zone of inhibition of tricarboxylic acid cycle activity may have been locally induced. In these dialysates, collected from probes closer to the epileptogenic region, the large increase in lactate/glucose ratios was a result of both increased lactate and reduced glucose levels.We conclude that regional variations in brain extracellular glucose concentrations may be of greater magnitude than previously believed and become even more accentuated in partial seizure patients. Data from concomitant assays of microdialysate lactate and glucose may aid in understanding cerebral metabolism.

  View details for Web of Science ID 000179307900011

  View details for PubMedID 12423386

• Ultradian sleep-cycle variation of serotonin in the human lateral ventricle NEUROLOGY Zeitzer, J. M., Maidment, N. T., Behnke, E. J., Ackerson, L. C., Fried, I., Engel, J., Wilson, C. L. 2002; 59 (8): 1272-1274

  Abstract

  Serotonin is thought to be intimately involved in the regulation of sleep and waking in humans, though the evidence for such is indirect. Using in vivo microdialysis, the authors show that serotonin in human ventricular CSF covaries with the state of consciousness. They hypothesize that CSF serotonin may be acting in an endocrine-like manner through activation of known leptomeningeal serotonin receptors and possibly participating in modulation of choroidal production of CSF.

  View details for Web of Science ID 000178726700033

  View details for PubMedID 12391366

• Diurnal variation of CSF hypocretin-1 (orexin A) levels in control and depressed subjects Salomon, R. M., Ripley, B., Kennedy, J. S., Schmidt, D., Zeitzer, J., Nishino, S., Mignot, E. AMER ACAD SLEEP MEDICINE. 2002: A12–A13

  View details for Web of Science ID 000174927200019

• Peak of circadian melatonin rhythm occurs later within the sleep of older subjects AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM Duffy, J. F., Zeitzer, J. M., Rimmer, D. W., Klerman, E. B., Dijk, D. J., Czeisler, C. A. 2002; 282 (2): E297-E303

  Abstract

  We investigated the relationship between sleep timing and the timing of the circadian rhythm of plasma melatonin secretion in a group of healthy young and older subjects without sleep complaints. The timing of sleep and the phase of the circadian melatonin rhythm were earlier in the older subjects. The relationship between the plasma melatonin rhythm and the timing of sleep was such that the older subjects were sleeping and waking earlier relative to their nightly melatonin secretory episode. Consequently, the older subjects were waking at a time when they had higher relative melatonin levels, in contrast with younger subjects, whose melatonin levels were relatively lower by wake time. Our findings indicate that aging is associated not only with an advance of sleep timing and the timing of circadian rhythms but also with a change in the internal phase relationship between the sleep-wake cycle and the output of the circadian pacemaker. In healthy older subjects, the relative timing of the melatonin rhythm with respect to sleep may not play a causal role in sleep disruption.

  View details for Web of Science ID 000173460600007

  View details for PubMedID 11788360

• The role of hypocretins (orexins) in sleep regulation and narcolepsy ANNUAL REVIEW OF NEUROSCIENCE Taheri, S., Zeitzer, J. M., Mignot, E. 2002; 25: 283-313

  Abstract

  The hypocretins (orexins) are two novel neuropeptides (Hcrt-1 and Hcrt-2), derived from the same precursor gene, that are synthesized by neurons located exclusively in the lateral, posterior, and perifornical hypothalamus. Hypocretin-containing neurons have widespread projections throughout the CNS with particularly dense excitatory projections to monoaminergic centers such as the noradrenergic locus coeruleus, histaminergic tuberomammillary nucleus, serotoninergic raphe nucleus, and dopaminergic ventral tegmental area. The hypocretins were originally believed to be primarily important in the regulation of appetite; however, a major function emerging from research on these neuropeptides is the regulation of sleep and wakefulness. Deficiency in hypocretin neurotransmission results in the sleep disorder narcolepsy in mice, dogs, and humans. The hypocretins are also uniquely positioned to link sleep, appetite, and neuroendocrine control. The aim of this review is to describe and discuss the current knowledge regarding the hypocretin neurotransmitter system in narcolepsy and normal sleep.

  View details for DOI 10.1146/annurev.neuro.25.112701.142826

  View details for Web of Science ID 000177354800009

  View details for PubMedID 12052911

• Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Klerman, E. B., Zeitzer, J. M., Duffy, J. F., Khalsa, S. B., Czeisler, C. A. 2001; 86 (7): 3166-3170

  Abstract

  The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  View details for Web of Science ID 000169838300042

  View details for PubMedID 11443183

• Salivary melatonin as a phase marker in older subjects Dineen, S. S., Duffy, J. F., Hall, E. F., Zeitzer, J. M., Polidori, P., Czeisler, C. A. AMER ACAD SLEEP MEDICINE. 2001: A197

  View details for Web of Science ID 000168230900332

• Serotonin and dopamine in the human cortex and limbic system during a 40h sleep deprivation challenge Zeitzer, J. M., Lopez-Rodriguez, F., Behnke, E., Ackerson, L. C., Fried, Engel, J., Wilson, C. L. AMER ACAD SLEEP MEDICINE. 2001: A76

  View details for Web of Science ID 000168230900124

• Fluctuations in neurotransmitter concentrations in human brain dialysates during sleep or wakefulness, during epileptic seizures or following cognitive challenge 9th International Conference on In Vivo Methods Maidment, N. T., Fried, I., LOPEZ, F., Zeitzer, J. M., Behnke, E. B., Ackerson, L. C., Engel, J., Wilson, C. L. UNIV COLLEGE DUBLIN. 2001: 160–161

  View details for Web of Science ID 000175403700077

• Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness BEHAVIOURAL BRAIN RESEARCH Cajochen, C., Zeitzer, J. M., Czeisler, C. A., Dijk, D. J. 2000; 115 (1): 75-83

  Abstract

  Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to <3 lux for several hours. Light exerted an acute alerting response as assessed by a reduction in the incidence of slow-eye movements, a reduction of EEG activity in the theta-alpha frequencies (power density in the 5-9 Hz range) as well as a reduction in self-reported sleepiness. This alerting response was positively correlated with the degree of melatonin suppression by light. In accordance with the dose response function for circadian resetting and melatonin suppression, the responses of all three indices of alertness to variations in illuminance were consistent with a logistic dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

  View details for Web of Science ID 000089374500009

  View details for PubMedID 10996410

• Plasma melatonin concentrations decline with age? Reply AMERICAN JOURNAL OF MEDICINE Zeitzer, J. M., Duffy, J. F., Klerman, E. B., Shanahan, T. L., Dijk, D. J., Czeisler, C. A. 2000; 109 (4): 345

  View details for DOI 10.1016/S0002-9343(00)00518-0

  View details for Web of Science ID 000089356600019

• Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression JOURNAL OF PHYSIOLOGY-LONDON Zeitzer, J. M., Dijk, D. J., Kronauer, R. E., Brown, E. N., Czeisler, C. A. 2000; 526 (3): 695-702

  Abstract

  Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

  View details for Web of Science ID 000089202500022

  View details for PubMedID 10922269

  View details for PubMedCentralID PMC2270041

• Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Zeitzer, J. M., Ayas, N. T., Shea, S. A., Brown, R., Czeisler, C. A. 2000; 85 (6): 2189-2196

  Abstract

  The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

  View details for Web of Science ID 000088460500023

  View details for PubMedID 10852451

• Do plasma melatonin concentrations decline with age? AMERICAN JOURNAL OF MEDICINE Zeitzer, J. M., Daniels, J. E., Duffy, J. F., Klerman, E. B., Shanahan, T. L., Dijk, D. J., Czeisler, C. A. 1999; 107 (5): 432-436

  Abstract

  Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults.We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years).We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin.These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

  View details for Web of Science ID 000083583900004

  View details for PubMedID 10569297

• Resetting the melatonin rhythm with light in humans JOURNAL OF BIOLOGICAL RHYTHMS Shanahan, T. L., Zeitzer, J. M., Czeisler, C. A. 1997; 12 (6): 556-567

  Abstract

  The endogenous circadian rhythm of melatonin in humans provides information regarding the resetting response of the human circadian timing system to changes in the light-dark (LD) cycle. Alterations in the LD cycle have both acute and chronic effects on the observed melatonin rhythm. Investigations to date have firmly established that the melatonin rhythm can be reentrained following an inversion of the LD cycle. Exposure to bright light and darkness given over a series of days can rapidly induce large-magnitude phase shifts of the melatonin rhythm. Even single pulses of bright light can shift the timing of the melatonin rhythm. Recent data have demonstrated that lower light intensities than originally believed are capable of resetting the melatonin rhythm and that stimulation of photopically sensitive photoreceptors (i.e., cones) is sufficient to reset the endogenous circadian melatonin rhythm. In addition to phase resetting, exposure to light of critical timing, strength, and duration can attenuate the amplitude of the endogenous circadian rhythm of melatonin. Measurement of melatonin throughout resetting trials provides a dynamic view of the resetting response of the human circadian pacemaker to light. Future studies of the melatonin rhythm in humans may further characterize the resetting response of the human circadian timing system to light.

  View details for Web of Science ID A1997YJ44900010

  View details for PubMedID 9406030

• Photopic transduction implicated in human circadian entrainment NEUROSCIENCE LETTERS Zeitzer, J. M., Kronauer, R. E., Czeisler, C. A. 1997; 232 (3): 135-138

  Abstract

  Despite the preeminence of light as the synchronizer of the circadian timing system, the phototransductive machinery in mammals which transmits photic information from the retina to the hypothalamic circadian pacemaker remains largely undefined. To determine the class of photopigments which this phototransductive system uses, we exposed a group (n = 7) of human subjects to red light below the sensitivity threshold of a scotopic (i.e. rhodopsin/rod-based) system, yet of sufficient strength to activate a photopic (i.e. cone-based) system. Exposure to this light stimulus was sufficient to reset significantly the human circadian pacemaker, indicating that the cone pigments which mediate color vision can also mediate circadian vision.

  View details for Web of Science ID A1997XV84100004

  View details for PubMedID 9310298

• Widespread expression of functional D-1-dopamine receptors in fetal rat brain DEVELOPMENTAL BRAIN RESEARCH Shearman, L. P., Zeitzer, J., Weaver, D. R. 1997; 102 (1): 105-115

  Abstract

  Maternal treatment with cocaine or the D1-dopamine receptor agonist, SKF 38393, induces expression of the immediate-early gene, c-fos, in fetal rodent brain. Our previous studies have focused on the suprachiasmatic nucleus late in gestation. In the present report, we examined the anatomical distribution of functional D1-dopamine receptors throughout fetal rat brain. Functional D1 receptors were defined using three complementary methods: in situ hybridization to detect D1 receptor mRNA, autoradiographic detection of 125I-SCH 23982 binding, and in situ hybridization to detect c-fos gene expression induced by maternal treatment with SKF 38393. D1-dopamine receptor binding, receptor mRNA, and SKF 38393-induced c-fos gene expression are widespread in fetal brain by late gestation. These data indicate that the fetal brain is sensitive to dopamine receptor activation, and suggest that gestational exposure to drugs of abuse acting via dopaminergic mechanisms may influence fetal brain function.

  View details for DOI 10.1016/S0165-3806(97)00091-6

  View details for Web of Science ID A1997XV52200011

  View details for PubMedID 9298239