Elizabeth B Klerman

Massachusetts General Hospital | MGH · Department of Neurology

Internal circadian phase assessment is increasingly acknowledged as a critical clinical tool for the diagnosis, monitoring, and treatment of circadian rhythm sleep−wake disorders and for investigating circadian timing in other medical disorders. The widespread use of in‐laboratory circadian phase assessments in routine practice has been limited, mo...

Adaptation of the circadian clock to the environment is essential for optimal health, well-being, and performance. Animal models demonstrate that a high-fat diet impairs circadian adaptation to advances of the light-dark cycle; it is unknown whether this occurs in humans. Utilizing a natural experiment that occurs when humans must advance their beh...

Study objectives Menopause is associated with nighttime sleep fragmentation, declining estradiol and impaired cognition. In a model of pharmacologically-induced estradiol suppression mimicking menopause, we examined the impact of menopause-pattern sleep fragmentation on daytime neurobehavioral performance and sleepiness in premenopausal women. Met...

Objective: The Mind after Midnight hypothesis proposes that nocturnal wakefulness increases the risk for dysregulated behaviors. Prior studies highlight a greater risk for suicide at night after adjusting for population wakefulness. How this risk varies hour to hour, differs across subgroups, or applies to other behaviors is unknown. Methods: Data...

Introduction The risk of cardiovascular disease increases during the menopausal transition. In addition to estradiol decline during the transition, there is increased sleep fragmentation due to hot flashes, without reduced total sleep time. We examined the impact of sleep fragmentation and estradiol decline on cardiometabolic outcomes in an experim...

Gunshots affect those directly involved in an incident and those in the surrounding community. The community-level impact of nighttime gunshots, which may be particularly disruptive to the sleep of nearby community members, is unknown. Our aim is to estimate the number of people potentially affected by nighttime gunshots and the relationship betwee...

Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with c...

Sleep behavior significantly impacts health and acts as an indicator of physical and mental well-being. Monitoring and predicting sleep behavior with ubiquitous sensors may therefore assist in both sleep management and tracking of related health conditions. While sleep behavior depends on, and is reflected in the physiology of a person, it is also...

Importance: Some medications have effects that depend on the time of day they are given. Current knowledge of the time-of-day effects of specific medications in hospitalized patients with cardiovascular disease is very limited. In hospitalized patients, increased medication efficiency might reduce dose (and associated side effects) and/or the lengt...

Developing interventions to prevent firearm-related violence and to address its consequences requires an improved understanding of when these violent events are most likely to occur. We explored gunshot events in 6 of the most populated cities in the United States by time of day, day of week, holiday/non-holiday, and month using publicly available...

The amount of time available in a day is fixed, and consequently, sleep is often sacrificed for waking activities. For college students, daily activities, comprised of scheduled classes, work, study, social, and other extracurricular events, are major contributors to insufficient and poor-quality sleep. We investigated the impact of daily schedules...

Objective Children with Down syndrome (DS) may experience changes in sleep architecture (i.e., different sleep stages) that then affect waketime functioning, including learning, mood, and disruptive behavior. For designing and testing interventions, it is important to document any differences in sleep architecture in children with DS with and witho...

Disclosure: L.K. Grant: Grant Recipient; Self; Brigham and Women’s Hospital, Women’s Health Access Matters. A. Cohn: None. S. Crawford: None. J. Harder: Consulting Fee; Self; Altman Health, O’Rouke & Hawk, LLP. Grant Recipient; Self; Brigham and Women’s Hospital, President and Fellows of Harvard College. Owner/Co-Owner; Self; Jessica Harder, MD. St...

Disclosure: S.A. Rahman: Consulting Fee; Self; Sultan & Knight Limited, Bambu Vault LLC, Lucidity Lighting Inc. Grant Recipient; Self; Seoul Semiconductor Co. Ltd, Biological Innovation and Optimization Systems, LLC, Merck & Co, Inc, Pfizer Inc, Vanda Pharmaceuticals Inc, Lighting Science Group. Speaker; Self; Starry Skies Lake Superior, University...

Objective: To develop and present consensus findings of the National Sleep Foundation sleep timing and variability panel regarding the impact of sleep timing variability on health and performance. Methods: The National Sleep Foundation assembled a panel of sleep and circadian experts to evaluate the scientific evidence and conduct a formal conse...

Objectives: Acute and chronic sleep loss and circadian timing interact such that, depending on their combination, small or very large performance decrements are observed in tasks of attention. Here, we tested whether such nonlinear interactions extend to a physiological measure of spontaneous visual attentional failures, indicating a fundamental pr...

Aging alters the amplitude and phase of centrally regulated circadian rhythms. Here we evaluate whether peripheral circadian rhythmicity in the plasma lipidome is altered by aging through retrospective lipidomics analysis on plasma samples collected in 24 healthy individuals (9 females; mean ± SD age: 40.9 ± 18.2 years) including 12 younger (4 fema...

Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data e...

Introduction Although suicides are more prevalent during the day, the risk of suicide is highest at night when adjusted for population wakefulness. It is unclear how nighttime patterns of suicide risk vary by demographic and clinical subgroups. Methods Population wakefulness data were combined with time of fatal injury data for 78,647 suicides fro...

Researchers in biology and medicine have increasingly focused on characterizing circadian rhythms and their potential impact on disease. Understanding circadian variation in metabolomics, the study of chemical processes involving metabolites may provide insight into important aspects of biological mechanism. Of scientific importance is developing a...

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https : //neuroscienceblueprint.n...

Context Perturbations to the hypothalamic-pituitary-adrenal (HPA) axis have been hypothesized to increase post-menopausal cardiometabolic risk. Although sleep disturbance, a known risk factor for cardiometabolic disease, is prevalent during the menopause transition, it is unknown whether menopause-related sleep disturbance and estradiol decline dis...

Objective The aim of this systematic review and metaanalysis is to summarize evidence regarding the relationship between psoriatic arthritis (PsA) and sleep problems. Methods We identified 36 eligible studies—26 cross-sectional, 7 cohort, and 3 interventional studies—in PubMed and Embase. Results The prevalence of self-reported sleep problems in...

Developing interventions to prevent firearm-related violence and to address its consequences requires an improved understanding of when these violent events are most likely to occur. We explored gunshot events by time of day, day of week, and holiday/non-holiday in six major US cities. We utilized publicly available police department datasets that...

″What time should I take my medicine?″ is an increasingly important question. Current knowledge of time – of – day effects for specific medications in hospitalized patients with cardiovascular disease is very limited. In such patients, increased medication efficiency could potentially reduce dose use and/or the length of time in the Intensive Care...

Background: Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to unders...

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer’s disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively n...

Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisr...

Circadian clocks drive cyclic variations in many aspects of physiology, but some daily variations are evoked by periodic changes in the environment or sleep-wake state and associated behaviors, such as changes in posture, light levels, fasting or eating, rest or activity and social interactions; thus, it is often important to quantify the relative...

Side effects of COVID-19 or other vaccinations may affect an individual’s safety, ability to work or care for self or others, and/or willingness to be vaccinated. Identifying modifiable factors that influence these side effects may increase the number of people vaccinated. In this observational study, data were from individuals who received an mRNA...

Mathematical techniques are often viewed as tools for data description and analysis. A valuable additional purpose is employing mathematical models as a research technique to both generate and test hypotheses. Mathematical model simulations have elucidated key processes controlling phase, amplitude, period, and synchrony in the circadian system fro...

Study Objectives In children, growth hormone (GH) pulses occur after sleep onset in association with slow wave sleep (SWS). There have been no studies in children to quantify the effect of disrupted sleep on GH secretion. This study aimed to investigate the effect of acute sleep disruption on GH secretion in pubertal children. Methods Fourteen hea...

Circadian rhythms influence and coordinate an organism’s response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically naïve to SARS-CoV-2 and prior to widespread v...

Prolonged exposure to chronic sleep restriction (CSR) and shiftwork are both associated with incident hypertension and cardiovascular disease. We hypothesized that the combination of CSR and shiftwork’s rotating sleep schedule (causing recurrent circadian disruption, RCD) would increase blood pressure, renal sodium retention, potassium excretion, a...

The field of “circadian medicine” is a recent addition to chronobiology and sleep research efforts. It represents a logical step arising from the increasing insights into the circadian system and its interactions with life in urbanised societies; applying these insights to the health/disease balance at home and in the medical practice (outpatient)...

Introduction: Disrupted sleep and excessive daytime sleepiness (EDS) are common and disabling symptoms of Parkinson's disease (PD). The relationships between subjective and objective assessments of sleep and sleepiness in PD are not well established. We aimed to examine the relationships between self-reported (subjective) and objective assessments...

Objective: Later circadian timing of energy intake is associated with higher body fat percentage. Current methods for obtaining accurate circadian timing are labor- and cost-intensive, limiting practical application of this relationship. This study investigated whether the timing of energy intake relative to a mathematically modeled circadian time...

Introduction Nocturnal wakefulness may be dangerous for vulnerable populations: the incident risk for suicide is highest at night after adjusting for population wakefulness, and nocturnal wakefulness is associated with suicidal ideation. These observations support the hypothesis that sleep- and circadian-dependent changes in mood, reward processing...

Introduction The risk for suicide is greatest at night after adjusting for population wakefulness, possibly due to sleep- and circadian-dependent changes in neurophysiology to promote sleep. Those who die by suicide at night, however, may differ by demographic and/or clinical characteristics from those who die by suicide during the day. Methods An...

Introduction There is a nocturnal peak in incident suicide risk after adjusting for population wakefulness (Perlis et al., 2016; Tubbs et al., 2020). This peak in risk is hypothesized to result from a series of negative changes in mood, reward processing, and executive function that occur at night and increase the propensity for dysregulated and vi...

Introduction Nocturnal wakefulness may mediate the relationship between disrupted sleep and suicide risk since nighttime is associated with a peak in negative mood and altered reward processing and executive function. One example is a wakefulness-adjusted nocturnal peak in population suicide risk measured from 2003-2010 (Perlis et al, 2016), but th...

Introduction Circadian rhythms have critical roles in human health. We quantified the effect of time-of-day of COVID-19 vaccination and other covariates on self-reported side effects post vaccination. Methods The dataset was created from MassGeneralBrigham (MGB) electronic health records and REDCap survey that collected self-reported symptoms for...

Context Body fat gain associated with menopause has been attributed to estradiol (E2) withdrawal. Hypoestrogenism is unlikely to be the only contributing factor, however. Objective Given the links between sleep and metabolic health, we examined the effects of an experimental menopausal model of sleep fragmentation on energy metabolism. Design Pre...

Background: During adolescence, sleep and circadian timing shift later, contributing to restricted sleep duration and irregular sleep-wake patterns. The association of these developmental changes in sleep and circadian timing with cognitive functioning, and consequently academic outcomes, has not been examined prospectively. The role of ambient li...

Circadian adaptation to shifted sleep/wake schedules may be facilitated by optimizing the timing, intensity and spectral characteristics of light exposure, which is the principal time cue for mammalian circadian pacemaker, and possibly by strategically timing non‐photic time cues such as exercise. Therefore, circadian phase resetting by light and e...

Chronic circadian disruption (CCD), such as occurs during rotating shiftwork, and insufficient sleep are each independently associated with poor health outcomes, including obesity and glucose intolerance. A potential mechanism for poor health is increased energy intake (i.e., eating), particularly during the circadian night, when the physiological...

Sufficient sleep with minimal interruption during the circadian/biological night supports daytime cognition and emotional regulation. Conversely, disrupted sleep involving significant nocturnal wakefulness leads to cognitive and behavioral dysregulation. Most studies to-date have examined how fragmented or insufficient sleep affects next-day functi...

Background: Nearly 14% of Americans experience chronic circadian disruption due to shift work, increasing their risk of obesity, diabetes, and other cardiometabolic disorders. These disorders are also exacerbated by modern eating habits such as frequent snacking and consumption of high-fat foods. Methods: We investigated the effects of recurrent...

Many people are concerned about whether they are getting “enough” sleep, and if they can “sleep too much.” These concerns can be approached scientifically using experiments probing long-term (i.e., multi-night) sleep homeostatic processes, since homeostatic processes move the system toward its physiological setpoint (i.e., between “not enough” and...

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time of day of vaccination has been reported to influence host immune respon...

Background Non‐invasive gamma frequency light and sound stimulation at 40Hz reduced Alzheimer’s disease (AD) pathology and improved performance during behavioral testing in mouse models of AD (Iaccarino et al., Nature , 2016; Martorell et al., Cell , 2019; Adaikkan et al., Neuron , 2019). Sensory stimulation inducing 40Hz entrainment reduced amyloi...

The circadian system is critical to timing biological functions in anticipation of daily environmental light changes, but much previous work on the development of molecular control inputs to shift the phase of the circadian system has applied model predictive control (MPC) without considering expected environmental light changes. We augment the MPC...

Study Objectives Clinical and population health recommendations are derived from studies that include self-report. Differences in question wording and response scales may significantly affect responses. We conducted a methodological review assessing variation in event definition(s), context (i.e., work- versus free-day), and timeframe (e.g., “in th...

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time-of-day of vaccination has been reported to influence host immune respon...

Insufficient sleep, which has been shown to adversely affect metabolism, is generally associated with prolonged exposure to artificial light at night, a known circadian disruptor. There is growing evidence suggesting that circadian disruption adversely affects metabolism, yet few studies have attempted to evaluate the adverse metabolic effects of i...

Study objectives: To determine whether there was evidence of circadian or sleep-regulatory dysfunction in sighted individuals with Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD). Methods: Three sighted individuals with signs and/or symptoms of N24SWD were studied. Thirty-five to three-hundred and thirty-two day laboratory and home-based assessm...

During the COVID-19 pandemic, schools around the world rapidly transitioned from in-person to remote learning, providing an opportunity to examine the impact of in-person vs. remote learning on sleep, circadian timing, and mood. We assessed sleep-wake timing using wrist-actigraphy and sleep diaries over 1-2 weeks during in-person learning (n=28) an...

Two patients with delayed sleep-wake phase disorder (DSWPD) demonstrated improvement in sleep quality and duration, reduction in symptoms, and elimination of the need for hypnotic or stimulant medications after changing their sleep schedules in response to the coronavirus disease 2019 (COVID-19) pandemic lockdown work schedule changes. These cases...

Circadian rhythms influence multiple essential biological activities, including sleep, performance, and mood. The dim light melatonin onset (DLMO) is the gold standard for measuring human circadian phase (i.e., timing). The collection of DLMO is expensive and time consuming since multiple saliva or blood samples are required overnight in special co...

Growth hormone (GH) is secreted by cells in the anterior pituitary on two time scales: discrete pulses over minutes that occur within a 24-hr pattern. Secretion reflects the balance of stimulatory and inhibitory inputs from the hypothalamus and is influenced by gonadal steroids, stress, nutrition, and sleep/wake states. We propose a novel approach...

This chapter discusses circadian rhythm sleep wake disorders (CRSWDs) as defined by the International Classification of Sleep Disorders (3rd ed.), including the etiology, clinical characteristics, diagnostic methods, and treatment options for both “intrinsic” (delayed and advanced sleep–wake phase disorders, non–24-hour sleep–wake rhythm disorder,...

The time of dim light melatonin onset (DLMO) is the gold standard for circadian phase assessment in humans, but collection of samples for DLMO is time and resource intensive. Numerous studies have attempted to estimate circadian phase from actigraphy data, but most of these studies have involved individuals on controlled and stable sleep-wake sched...

Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to...

Introduction Actigraphy is a non-invasive method that allows long-term recordings of activity, light, and other variables in diverse environments. In real-world settings, activity usually has a 24-hour rhythm that may arise from sleep/wake-associated behavior and/or circadian rhythmicity. We tested for an independent circadian component using data...

Introduction Chronic sleep restriction (CSR) and recurrent circadian disruption (RCD; e.g., rotating shiftwork) can increase an individual’s risk of cardiovascular and kidney disease. However, no study has assessed whether CSR and RCD together increase blood pressure (BP) and alter renal function (RF). We tested the hypotheses that the combination...

Introduction Sleep disturbance is associated with poor mental health and may contribute to initiating or continuing use/abuse of alcohol and drugs. Using data from a nationwide survey, we examined the relationship between sleep disturbance and suicide behaviors among youth and adults, including those who report drug/alcohol use and abuse. Methods...

Background: Both sleep disturbance and menopause have independently been associated with weight gain in women. Possible mechanisms contributing to this weight gain may be changes in resting energy expenditure (REE) and/or nutrient utilization. Therefore, in the current study we aimed to examine the effects of experimentally induced sleep fragmentat...

Sleep is one of the key underpinnings of human health, yet sleep disturbances and impaired sleep are rampant in modern life. Healthy sleep is a whole-body process impacted by circadian rhythm, daily activities, and emotional well-being, among others. When properly aligned, these work in concert to produce restorative and refreshing sleep. When not...

Study Objectives Sleep regularity predicts many health-related outcomes. Currently, however, there is no systematic approach to measuring sleep regularity. Traditionally, metrics have assessed deviations in sleep patterns from an individual’s average. Traditional metrics include intra-individual standard deviation (StDev), Interdaily Stability (IS)...

Non-invasive G amma EN trainment U sing S ensory stimulation (GENUS) at 40Hz reduced Alzheimer’s disease (AD) pathology such as amyloid and tau levels, prevented cerebral atrophy and improved performance during behavioral testing in mouse models of AD. We report data from a randomized, placebo-controlled trial (n = 15) in volunteers with probable m...

BACKGROUND Shift work is associated with sleep disorders which impair alertness and increase risk of chronic physical and mental health disease. In health care workers, shift work and its associated sleep loss decreases provider wellness and can compromise patient care. Pharmacological sleep aids or substances such as alcohol are often used to impr...

Polyphasic sleep is the practice of distributing multiple short sleep episodes across the 24-hour day rather than having one major and possibly a minor (“nap”) sleep episode each day. While the prevalence of polyphasic sleep is unknown, anecdotal reports suggest attempts to follow this practice are common, particularly among young adults. Polyphasi...

Objectives: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians. Methods: Data from 294 resident-physicians were an...