Daniel F. Kripke's research while affiliated with University of California, San Diego and other places

Publications (346)

Article
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Key points: Exercise elicits circadian phase-shifting effects, but additional information is needed. The phase-response curve describing the magnitude and direction of circadian rhythm phase shifts, depending on the time of the zeigeber (time cue) stimulus, is the most fundamental chronobiological tool for alleviating circadian misalignment and re...
Article
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This is a review of hypnotic drug risks and benefits. Almost every month, new information appears about the risks of hypnotics (sleeping pills). The most important risks of hypnotics include excess mortality (especially overdose deaths, quiet deaths at night, and suicides), infections, cancer, depression, automobile crashes, falls, other accidents,...
Article
Background: Peripartum major depression (MD) disables mothers and impairs emotional and neurocognitive development of offspring. We tested the hypothesis that critically-timed wake therapy (WT) relieves peripartum MD by altering melatonin and sleep timing, differentially, in antepartum vs. postpartum depressed patients (DP). Methods: In a univer...
Article
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Hypnotics (sleeping pills) are prescribed widely, but the economic costs of the harm they have caused have been largely unrecognized. Randomized clinical trials have observed that hypnotics increase the incidence of infections. Likewise, hypnotics increase the incidence of major depression and cause emergency admissions for overdoses and deaths. Ep...
Chapter
Dozens of epidemiologic studies spanning over 50 years have established that both short sleep (<6 h of self-reported sleep) and long sleep (≥8 h of self-reported sleep) have been associated with increased mortality and multiple morbidities. Consistently, long sleep has been associated with greater risks than short sleep. Although epidemiologic stud...
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Introduction Critically-timed wake therapy improves mood in one day in most depressed patients (DP). We tested the hypothesis that early-night wake therapy (EWT: sleep 3:00 - 7:00 am) vs. late-night wake therapy (LWT: sleep 9:00 pm - 01:00 am) improves mood more in antepartum vs. postpartum depression by differentially altering melatonin and sleep...
Article
Full-text available
Hypnotics (sleeping pills) are prescribed widely, but the economic costs of the harm they have caused have been largely unrecognized. Randomized clinical trials have proven that hypnotics increase the incidence of infections. Likewise, hypnotics increase the incidence of major depression and cause emergency admissions for overdoses and deaths. Epid...
Article
Full-text available
This is a review of hypnotic drug risks and benefits, reassessing and updating advice presented to the Commissioner of the Food and Drug Administration (United States FDA). Almost every month, new information appears about the risks of hypnotics (sleeping pills). The most important risks of hypnotics include excess mortality, especially overdose de...
Article
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Bipolar disorder is a common mental disorder characterized by mood disturbances with alternating episodes of mania and depression. Circadian rhythms are rhythms of about 24 h found in many body functions.We repeatedly measured circadian rhythms in bipolar disorder patients during hospitalization. Acute manic episodes were associated with circadian...
Article
Full-text available
This is a review of hypnotic drug risks and benefits, reassessing and updating advice presented to the Commissioner of the Food and Drug Administration (United States FDA). Almost every month, new information appears about the risks of hypnotics (sleeping pills). This review includes new information on the growing USA overdose epidemic, eight new e...
Article
A sudden rush of newly-published research has given us much more understanding of what it means to be an “evening person” or “night owl”. An evening person feels more alert as evening arrives, may have trouble getting to sleep at a normal bedtime, and may have trouble getting up in the morning. The contrast is a “morning person” who wakes up early...
Article
Accepted Manuscript Title: I petitioned the FDA to restrict hypnotics: here is why Author: Daniel F. Kripke PII: DOI: Reference: S1389-9457(15)02088-2 http://dx.doi.org/doi: 10.1016/j.sleep.2015.12.011 SLEEP 2982 To appear in: Sleep Medicine Please cite this article as: Daniel F. Kripke, I petitioned the FDA to restrict hypnotics: here is why, Slee...
Article
Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard rat...
Article
The common assumption that population sleep duration has declined in the past few decades has not been supported by recent reviews, which have been limited to self-reported data. The aim of this review was to assess whether there has been a reduction in objectively recorded sleep duration over the last 50+ years. The literature was searched for stu...
Article
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Suvorexant is a novel dual orexin receptor antagonist (DORA) newly introduced in the U.S. as a hypnotic, but no claim of superiority over other hypnotics has been offered. The manufacturer argued that the 5 and 10 mg starting doses recommended by the FDA might be ineffective. The manufacturer's main Phase III trials had not even included the 10 mg...
Article
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Objectives In its guidelines on the use of portable monitors to diagnose obstructive sleep apnoea, the American Academy of Sleep Medicine endorses home polygraphy with type III devices recording at a minimum airflow the respiratory effort and pulse oximetry, but advises against simple pulse oximetry. However, oximetry is widely available and simple...
Article
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Seasonal effects on mood have been observed throughout much of human history. Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight). We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of...
Article
In this issue, Özdemir and colleagues have shown that treatment of severe major depression can now be greatly improved by safe, simple, and readily available bright light treatment. Patients may benefit within a week. Moreover, the benefit persisted throughout 8 weeks of observation even after the bright light treatment was discontinued. What seeme...
Article
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Concern that disturbances of sleep and light exposures at night might increase cancer risks have been expressed, but little actual exposure data has been collected. Measurements from a representative population sample were examined to understand the magnitude of in-bed light exposure at night and possible correlates. From 1990 to 1994, a home surve...
Article
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The diagnostic boundaries of sleep disorders are under considerable debate. The main sleep disorders are partly heritable; therefore, defining heritable pathophysiologic mechanisms could delineate diagnoses and suggest treatment. We collected clinical data and DNA from consenting patients scheduled to undergo clinical polysomnograms, to expand our...
Article
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People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delay...
Article
“Rebound” is NOT an appropriate criterion for withdrawal insomnia Daniel F. Kripke, M.D. Viterbi Family Sleep Center Scripps Clinic W-207 10666 North Torrey Pines Road La Jolla, CA 92037, USA E-mail address: dkripke1@san.rr.com Dr. Mayer’s interesting discussion of my letter in the September, 2014 Sleep Med. was helpful in clarifying problems with...
Article
HYPNOTICS CAUSE INSOMNIA: EVIDENCE FROM CLINICAL TRIALS Daniel F. Kripke Viterbi Family Sleep Center Scripps Clinic W-207 10666 North Torrey Pines Road La Jolla, California 92037, USA email: dkripke1@san.rr.com Keywords: Insomnia, withdrawal, hypnotics, ramelteon, eszopiclone, suvorexant Submitted to Sleep Medicine as an Editorial, Controversies ar...
Article
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Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relat...
Article
Epidemiologic studies have consistently shown that sleeping < 7 hr and ≥ 8 hr is associated with increased mortality and morbidity. The risks of short sleep may be consistent with results from experimental sleep deprivation studies. However, there has been little study of chronic moderate sleep restriction and no evaluation of older adults who migh...
Article
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Background There are several indications that malfunctions of the circadian clock contribute to depression. To search for particular circadian gene polymorphisms associated with depression, diverse polymorphisms were genotyped in two samples covering a range of depressed volunteers and participants with normal mood. Methods Depression mood self-ra...
Article
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Bright light in the blue-green range, administered in the early morning hours (prior to waking) may be particularly effective in shifting circadian rhythms and may increase gonadotropin production. Accordingly, we tested the feasibility and utility of a mask that emits bright blue/green light (compared to a similar mask that emitted a dim red light...
Article
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Delayed sleep phase disorder (DSPD) is a condition in which patients often fall asleep some hours after midnight and have difficulty waking up in the morning. Circadian chronotype questionnaires such as Horne-Östberg Morningness-Eveningness Questionnaire (MEQ) and Basic Language Morningness (BALM) scale have been used for screening for DSPD. This s...
Article
Objective: The use of subphenotypes may be an effective approach for genetic studies of complex diseases. Manic episodes with a seasonal pattern may distinguish phenotypic subgroups of bipolar subjects that may also differ genetically. Method: We have performed a genome-wide association study using GAIN genotype data from the Bipolar Genome Stud...
Article
Background: An estimated 6% – 10% of U.S. adults took a hypnotic drug for poor sleep in 2010. At least 18 studies have reported significant (p<0.05) associations of hypnotic usage with increased mortality. However, most lacked data on newer, supposedly safer, short-acting drugs, and had limited control for confounding by health status. Furthermore,...
Article
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An estimated 6%-10% of US adults took a hypnotic drug for poor sleep in 2010. This study extends previous reports associating hypnotics with excess mortality. A large integrated health system in the USA. Longitudinal electronic medical records were extracted for a one-to-two matched cohort survival analysis. Subjects (mean age 54 years) were 10 529...
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It has been reported that rs4446909, a single nucleotide polymorphism (SNP) in the promoter of acetylserotonin methyltransferase (ASMT), influences the expression of the ASMT enzyme. The common G allele is associated with lower ASMT activity, and therefore, diminishes conversion of N-acetylserotonin to melatonin. The G allele was associated with re...
Article
Bipolar disorder (BD) is characterized by disruptions in circadian rhythms such as sleep and daily activity that often normalize after lithium treatment in responsive patients. As lithium is known to interact with the circadian clock, we hypothesized that variation in circadian 'clock genes' would be associated with lithium response in BD. We deter...
Article
Both delayed sleep phase syndrome (DSPS) and seasonal affective disorder (SAD) may manifest similar delayed circadian phase problems. However, the relationships and co-morbidity between the two conditions have not been fully studied. The authors examined the comorbidity between DSPS and SAD. We recruited a case series of 327 DSPS and 331 controls w...
Article
Hoaki and colleagues recently showed that hyperthermic temperament was strongly associated with increased illumination among a group of healthy subjects. This is interesting because it broadens the context of case reports suggesting that bright light may at times trigger hypomania or mania. There have been several studies which have suggested a co...
Article
The folk belief that we should sleep 8 h seems to be incorrect. Numerous studies have shown that self-reported sleep longer than 7.5 h or shorter than 6.5 h predicts increased mortality risk. This study examined if prospectively-determined objective sleep duration, as estimated by wrist actigraphy, was associated with mortality risks. From 1995-199...
Article
Wrist actigraphy is employed increasingly in sleep research and clinical sleep medicine. Critical evaluation of the performance of new actigraphs and software is needed. Actigraphic sleep-wake estimation was compared with polysomnographic (PSG) scoring as the standard in a clinical sleep laboratory. A convenience sample of 116 patients undergoing c...
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The PER2 gene has been reported to influence diurnal preference. In this study, we have attempted to characterize the associations between the PER2 gene polymorphisms and diurnal preference in a population of healthy young subjects, controlling for the social and environmental confounding factors. Subjects were 299 students in a college, carefully...
Article
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Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on th...
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The genetic susceptibility factors underlying sleep disorders might help us predict prognoses and responses to treatment. Several candidate polymorphisms for sleep disorders have been proposed, but there has as yet inadequate replication or validation that the candidates may be useful in the clinical setting. To assess the validity of several candi...
Article
Although self-reported long sleep is associated with increased morbidity and mortality, little is known about the objective sleep patterns and daytime functioning of long sleepers, particularly those aged ≥50 years. Our primary aim was to compare the objective and subjective sleep patterns of a sample (n= 35) of middle- to older-aged adults who rep...
Article
To describe which dietary nutrient variables are related to subjective and objective habitual sleep and subjective and objective napping. Participants were 459 post-menopausal women enrolled in the Women's Health Initiative. Objective sleep was estimated using one week of actigraphy. Subjective sleep was prospectively estimated with a daily sleep d...
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To examine the influence of chronic time-in-bed (TIB) restriction on selected health-related outcome variables in older long sleepers. Randomized, controlled trial. Home-based. Forty-two older adults (aged 50-70 y) who reported sleeping at least 8.5 hours. Following extensive screening, participants were assessed for 10 weeks. During a two-week bas...
Article
Recent meta-analyses raising concern about risks of hypnotics suggest a need for more clarification of these risks. Because of preliminary suggestions that eszopiclone causes infections, we studied US Food and Drug Administration files on the 4 most-recently approved hypnotics, combined with published studies, to compile the risk ratios of infectio...
Article
Actigraphy has become an important tool in sleep research, however, most actigraphic models have had little evaluation of their sleep scoring software. Some reports have described poor agreement of actigraph and polysomnogram (PSG) results. In this study, we examined the accuracy of the Actiwatch-L instrument with Actiware((R)) software version 5.0...
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Seasonal variation in suicides has been shown in many countries. We assessed the seasonality and the variation with latitude in suicides and homicides, and the impact of alcohol on the seasonality in suicides. Official computerized registers on causes of death in all Greenland during 1968-2002 were used. Sales data on beer from one of the major foo...
Data
SNPs of bipolar participants associated with the BALM. 30 SNPs tested for association with the BALM morningness-eveningness scale are listed, with the SNPs significant after control for multiple comparisons highlighted in green.
Data
SNPs associated with transmission of bipolar disorder. 198 polymorphisms entered into TDT tests for association with bipolar disorder are listed. SNPs nominally significant are highlighted in yellow and the SNP significant after control for multiple comparisons is highlighted in green.
Data
SNPs associated with unipolar depression. 62 polymorphisms tested for association with recurrent unipolar depression are listed, with SNPs nominally significant highlighted in yellow.
Article
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Clinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective diso...
Article
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Type 2 diabetes and obstructive sleep apnea (OSA) are frequently comorbid conditions. OSA is associated with increased insulin resistance, but studies of continuous positive airway pressure (CPAP) have shown inconsistent effects on glycemic control. However, endpoints such as hemoglobin A1c and insulin sensitivity might not reflect short-term chang...
Article
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The purpose of this study was to test the hypothesis that disturbances in levels of plasma melatonin differentiate pregnant and postpartum women with major depression from matched pregnant and postpartum healthy comparison women. Participants were 25 pregnant women (10 with major depression, 15 healthy) and 24 postpartum women (13 with major depres...
Article
Fifteen epidemiologic studies have associated hypnotic drugs with excess mortality, especially excess cancer deaths. Until recently, insufficient controlled trials were available to demonstrate whether hypnotics actually cause any cancers. The US Food and Drug Administration (FDA) Approval History and Documents were accessed for zaleplon, eszopiclo...
Article
The aim of this study was to investigate the effects of 8 weeks of moderate restriction of time in bed (TIB) on glucose tolerance and insulin sensitivity in healthy older self-reported long sleepers. Forty-two older adults (ages 50-70 years) who reported average sleep durations of >or=8.5 h per night were assessed. Following a 2-week baseline, part...
Article
The symptoms of restless legs syndrome (RLS) have a circadian pattern and central nervous system dopamine has been implicated in the pathogenesis of the condition. We sought to characterize circadian variation in dopamine and related compounds in human cerebro-spinal fluid (CSF). CSF was continuously withdrawn for 22 h from an implanted lumbar intr...
Article
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Delayed sleep phase disorder (DSPD) is a condition in which patients have difficulty falling asleep before the early morning hours and commonly have trouble awakening before late morning or even early afternoon. Several studies have suggested that variations in habitual bedtime are 40-50% heritable. We recruited a case series of 205 participants, a...
Article
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The aim of this study was to access how self-reported sleep latency (SRSL) was affected by sleep habits, mood, and circadian rhythm in postmenopausal women. Subjects (n=384, 67.9+/-7.7 yr) completed sleep and mood questionnaires, sleep log and actigraphic data. The major urinary melatonin metabolite (6-sulphatoxymelatonin, aMT6s) was assayed in fra...
Article
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The aim of this open trial was to examine the influence of acute bright light exposure on anxiety in older and young adults. This study was ancillary to a complex 5-day laboratory experiment testing phase-responses to light at all times of the day. On 3 consecutive days, participants were exposed to bright light (3,000 lux) for 3 hours. The Spielbe...