Rhythm Sleep-wake Disorders Research Articles

Melatonin in the treatment of Circadian Rhythm Sleep-Wake Disorders – the principles of choosing the right time and dose of administration

Aim. Circadian Rhythm Sleep-Wake Disorders (CRSWD) are a common group of sleep disorders. The aim of this article is to present the principles for treatment of CRSWD with melatonin. Methods. Review of data from randomised, placebo-controlled clinical trials. Results. The main indication for the use of melatonin is a treatment of Delayed Sleep-Wake Phase Disorder (DSWPD). Melatonin is also recommended for the treatment of Irregular Sleep-Wake Rhythm Disorder and Non-24-Hour Sleep-Wake Rhythm Disorder. However, in the treatment of Advanced Sleep-Wake Phase Disorder melatonin plays a secondary role. The therapeutic effect of melatonin primarily depends on the appropriate time of its administration. In DSWPD it should be administered even 6–8 hours before the scheduled sleep time. The available data does not indicate that the melatonin’s therapeutic effect is strongly correlated with the used dose and the recommended doses fall within a wide range of 0.5 to 10 mg. However, usually higher doses, e.g. 5 mg, are beneficial in the first 3–6 weeks of treatment. In neuropsychiatric disorders in children, dosage even up to 10 mg is recommended. Melatonin is also an effective form for relieving symptoms of exogenous CRSWD: shift work disorder and jet lag disorder. Prolonged-release formulation of melatonin in a 2 mg dose is registered for the treatment of insomnia patients aged 55 years and older. Conclusions. Treatment of CRSWD is based primarily on chronotherapeutic interventions. They include phototherapy, light avoidance, melatonin treatment and behavioural interventions that influence, among other things, the rhythm of meals, physical and social activity.

Chapter 24 - Clinical neurophysiology of circadian rhythm sleep–wake disorders

Circadian rhythms are the endogenous near-24-h oscillations in physiologic processes. In mammals the suprachiasmatic nucleus serves as the primary circadian pacemaker, and it maintains rhythmicity at a genetic level through a complex transcription-translation feedback loop of core circadian clock genes. The circadian clock is entrained to the environment through daily exposure to light and melatonin. Disruption of these endogenous rhythms or the ability to entrain to the surrounding environment results in the circadian rhythm sleep-wake disorders (CRSWDs). Patients with CRSWDs can present with either late sleep/wake times (delayed sleep-wake phase disorder), early sleep/wake times (advanced sleep-wake phase disorder), inconsistent sleep/wake times (irregular sleep-wake rhythm disorder) or sleep-wake times that move progressively later each day (non-24-h sleep-wake rhythm disorder). Diagnosis of these disorders relies on the use of sleep logs and/or actigraphy to demonstrate the daily patterns of rest and activity. Treatment of the CRSWDs focuses on sleep hygiene and strategically timed light and melatonin.

Diagnostic et comorbidités des troubles du rythme veille-sommeil

Circadian rhythm sleep disorders (CRSD) result from a disturbed endogenous clock (intrinsic CRSD) or from a misalignment between the biological clock and an imposed environment (extrinsic CRSD). Among intrinsic CRSD, one distinguishes the delayed sleep-wake phase disorder, the advanced sleep-wake phase disorder, the irregular sleep-wake rhythm disorder and the non-24-hour sleep-wake rhythm disorder. Shift work disorder, jet lag disorder and circadian sleep-wake disorder not otherwise specified are extrinsic CRSD. Prevalences of the different CRSD remain largely unknown. Some CRSD are particularly frequent such as sleep delayed phase syndrome in adolescents. Overall, CRSD are probably under-diagnosed. CRSD generate insomnia and excessive daytime somnolence. A biological clock dysfunction has to be evoked in case of insomnia or sleepiness. Furthermore, as CRSD can overlap with other sleep disorders, their diagnosis and treatment are essential. CRSD cause significant mental, physical or socio-professional sufferings. They are frequently associated with comorbidities, mainly neurodevelopmental, psychiatric and neurodegenerative disorders. Regarding neurodevelopmental comorbidities, therapy using a chronobiological approach is complementary to the usual clinical care. It helps to limit the significant impact of CRSD on quality of live, daytime functioning, social interactions and neurocognitive difficulties in the children. In psychiatry, sleep disorders and circadian rhythms sleep-wake disorders are a factor of vulnerability, of suicidal risk, of relapse and pharmacoresistance. Thus, diagnosis of CRSD associated with a psychiatric disorder is of major importance. Treatment using a chronobiological approach reinforcing the entrainment of the sleep-wake cycle is complementary to usual treatments. Sleep disorders and circadian sleep-wake rhythm disorders can be a preclinical sign of Alzheimer's and Parkinson's disease. In the elderly, a beginning neurodegenerative disorder can be associated with a CRSD and complaints of sleepiness, nocturnal awakenings and/or irregular sleep-wake cycles. Patients affected by neurogenerative disorders are particularly vulnerable for having CRSD. Data from different studies suggest that CRSD participate in pathophysiology of Alzheimer's disease. Even though treatment of CRSD associated with neurodegenerative disorders is entirely part of the treatment strategy, it remains uncertain to which extend this treatment may impact disease progression.

Le traitement par la lumière des troubles circadiens du rythme veille-sommeil

Phototherapy is one treatment of circadian sleep-wake disorders, which is based on consensual and numerous scientific and clinical evidences. Phototherapy efficiency depends on several light characteristics based on intensity, length of exposure, time of exposure and wavelength. Phototherapy is potentially indicated in the following circadian disorders: advanced sleep-wake phase disorder (ASWPD), delayed sleep-wake phase disorder (DSWPD), non-24-hour sleep-wake rhythm disorder (N24SWD), jet-lag and night-shift work sleep-wake disorders (NSSWD). Phototherapy, acting via the retina, may be avoided in patients with retina disorders, an ophthalmologist should be consulted.

Treatment outcome of non-24-hour sleep–wake rhythm disorder: a retrospective study of 24 consecutive cases in a sleep clinic

Treatment outcome of non-24-hour sleep–wake rhythm disorder: a retrospective study of 24 consecutive cases in a sleep clinic

Low dose of aripiprazole advanced sleep rhythm and reduced nocturnal sleep time in the patients with delayed sleep phase syndrome: an open-labeled clinical observation.

ObjectivesDelayed sleep phase syndrome (DSPS) is a chronic dysfunction of circadian rhythm of the subject that impairs functioning in social, occupational, or other spheres. High rate of depression is found among DSPS patients. Aripiprazole (APZ), a second-generation antipsychotic, is effective in treatment of depression as well as schizophrenia. Recently, few case reports show the effectiveness of APZ in treating DSPS and non-24-hour sleep–wake rhythm disorder. Therefore, we tried to treat DSPS with depression using APZ.MethodsTwelve subjects (including four women) aged 19–64 years were included. The subjects were prescribed initially 0.5–3 mg of APZ once a day with subsequent dose adjustments.ResultsSleep onset, midpoint of sleep, and sleep offset were significantly advanced by 1.1, 1.8, and 2.5 hours, respectively. Unexpectedly, sleep duration became significantly shorter by 1.3 hours after treatment. Their depressive moods showed an unremarkable change.ConclusionLow dose of APZ advanced the sleep rhythm and reduced nocturnal sleep time in the subjects with DSPS. Since it is not easy for physicians to treat prolonged sleep duration often associated with DSPS, this medication would become a new therapeutic option for these patients.

Sleep-wake rhythm after extracorporeal circulation in New Zealand rabbits

To evaluate the change of sleep-wake rhythm after extracorporeal circulation (ECC) in New Zealand rabbits, and to explore the role of clock genes in sleep-wake rhythm disorder by ECC. Methods: A total of 54 New Zealand rabbits were randomly divided into 3 groups: a normal group (Group N), a sham group (Group S) and a model group (Group ECC). Electrocorticogram (ECOG), electroophthalmogram (EOG) and electromyogram (EMG) were respectively recorded by multipurpose EEG recorder, and the sleep-wake rhythm was also recorded. The mRNA and protein expressions of period1 (Per1) and cryptochrome1 (Cry1) were detected by semi-quantitative reverse transcriptase PCR (RT-PCR) and Western blot in pineal gland of rabbits. The differences between the 3 groups were compared. Results: 1) Compared with the Group N and Group S at 24, 48 h respectively, the total amount of sleep (TAS), light time, slow wave sleep (SWS) in the Group ECC at 24, 48 h were significantly reduced (all P<0.05), and the proportion of light sleep increased (all P<0.05), the proportion of SWS decreased (all P<0.05); 2) Compared with the Group N and Group S, the expression of Per1 mRNA in the Group ECC at 24, 48 h and Cry1 mRNA at 24 h significantly increased (all P<0.05); 3) Compared with the Group N and Group S, the expression of Per1 protein in the Group ECC at 48 h and Cry1 protein at 24 h significantly increased (all P<0.05); 4) In the Group ECC, the sleep-wake rhythm disorder and clock genes expression were ameliorated at 72 h after surgery. Conclusion: ECC can cause sleep-wake rhythm disorder in New Zealand rabbits, which may be related to the abnormal expression of Per1 and Cry1, and their transcription proteins.

1131 Restoration of Normal Sleep Pattern in a Patient with Non-24-Hour Sleep-Wake Rhythm Disorder and Mood Disorder after Treatment with Aripiprazole

1131 Restoration of Normal Sleep Pattern in a Patient with Non-24-Hour Sleep-Wake Rhythm Disorder and Mood Disorder after Treatment with Aripiprazole

What We Learn from the CTAD (Clinical Trials Alzheimer's Disease) 2018.

Several ongoing clinical development programs are investigating potential disease-modifying treatments for Alzheimer's disease (AD), including lanabecestat (AZD3293/LY3314814). Lanabecestat is a brain-permeable oral inhibitor of human beta-site amyloid (Aβ) precursor protein-cleaving enzyme 1 (BACE1) that reduces Aβ production. As a potent BACE1 inhibitor, lanabecestat significantly reduced soluble Aβ species and soluble amyloid precursor proteins (sAPPβ) in mouse, guinea pig, and dog in a time- and dose-dependent manner. Significant reductions in plasma and cerebrospinal fluid (CSF) Aβ1-40 and Aβ1-42 were observed in Phase 1 studies of healthy subjects and AD patients treated with lanabecestat. Three lanabecestat trials are ongoing and intended to support registration in Early AD: (1) Phase 2/3 study in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia (AMARANTH, NCT02245737); (2) Delayed-start extension study (AMARANTH-EXTENSION, NCT02972658) for patients who have completed treatment in the AMARANTH Study; and (3) Phase 3 study in mild AD dementia (DAYBREAK-ALZ, NCT02783573). This review will discuss the development of lanabecestat, results from the completed nonclinical and clinical studies, as well as describe the ongoing Phase 3 clinical trials.

Non-24-Hour Sleep-Wake Rhythm Disorder in the Totally Blind: Diagnosis and Management.

Several aspects of human physiology and behavior are dominated by 24-h circadian rhythms with key impacts on health and well-being. These include mainly the sleep–wake cycle, vigilance and performance patterns, and some hormone secretions. The rhythms are generated spontaneously by an internal “pacemaker,” the suprachiasmatic nuclei within the anterior hypothalamus. This master clock has, for most humans, an intrinsic rhythm slightly longer than 24 h. Daily retinal light exposure is necessary for the synchronization of the circadian rhythms with the external 24-h solar environment. This daily synchronization process generally poses no problems for sighted individuals except in the context of jetlag or working night shifts being conditions of circadian desynchrony. However, many blind subjects with no light perception had periodical circadian desynchrony, in the absence of light information to the master clock leading to poor circadian rhythm synchronization. Affected patients experience cyclical or periodic episodes of poor sleep and daytime dysfunction, severely interfering with social, academic, and professional life. The diagnosis of Non-24 Sleep–Wake Rhythm Disorder, also named free-running disorder, non-entrained disorder, or hypernycthemeral syndrome, remains challenging from a clinical point of view due to the cyclical symptoms and should be confirmed by measurements of circadian biomarkers such as urinary melatonin to demonstrate a circadian period outside the normal range. Management includes behavioral modification and melatonin. Tasimelteon, a novel melatonin receptor 1 and 2 agonist, has demonstrated its effectiveness and safety with an evening dose of 20 mg and is currently the only treatment approved by the FDA and the European Medicines Agency.

Irregular sleep-wake rhythm disorder in a young woman with Townes-Brocks-syndrome

Irregular sleep-wake rhythm disorder in a young woman with Townes-Brocks-syndrome

Circadian Rhythm Sleep-Wake Disorders.

The endogenous circadian rhythms are one of the cardinal processes that control sleep. They are self-sustaining biological rhythms with a periodicity of approximately 24 hours that may be entrained by external zeitgebers (German for time givers), such as light, exercise, and meal times. This article discusses the physiology of the circadian rhythms, their relationship to neurologic disease, and the presentation and treatment of circadian rhythm sleep-wake disorders. Classic examples of circadian rhythms include cortisol and melatonin secretion, body temperature, and urine volume. More recently, the impact of circadian rhythm on several neurologic disorders has been investigated, such as the timing of occurrence of epileptic seizures as well as neurobehavioral functioning in dementia. Further updates include a more in-depth understanding of the symptoms, consequences, and treatment of circadian sleep-wake disorders, which may occur because of extrinsic misalignment with clock time or because of intrinsic dysfunction of the brain. An example of extrinsic misalignment occurs with jet lag during transmeridian travel or with intrinsic circadian rhythm sleep-wake disorders such as advanced or delayed sleep-wake phase disorders. In advanced sleep-wake phase disorder, which is most common in elderly individuals, sleep onset and morning arousal are undesirably early, leading to impaired evening function with excessive sleepiness and sleep-maintenance insomnia with early morning awakening. By contrast, delayed sleep-wake phase disorder is characterized by an inability to initiate sleep before the early morning hours, with subsequent delayed rise time, leading to clinical symptoms of severe sleep-onset insomnia coupled with excessive daytime sleepiness in the morning hours, as patients are unable to "sleep in" to attain sufficient sleep quantity. Irregular sleep-wake rhythm disorder is misentrainment with patches of brief sleep and wakefulness spread throughout the day, leading to unstable sleep and waking behavioral patterns and an entirely idiosyncratic sleep-wake schedule. Familiarity with these major circadian rhythm sleep-wake disorder phenotypes and their overlap with other neurologic disorders is essential for the neurologist so that clinicians may intervene and improve patient functioning and quality of life.

0701 CIRCADIAN TAU DIFFERENCES IN BIOLOGICAL, BEHAVIOURAL AND SLEEPINESS RHYTHMS IN DELAYED SLEEP-WAKE PHASE DISORDER AND NON-24-HOUR SLEEP-WAKE RHYTHM DISORDER PATIENTS

In this study we investigated biological, sleepiness and behavioural rhythm period lengths (i.e., taus) of Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD) patients and healthy control sleepers. We also ran cross-correlation analyses between different rhythm variables to examine phase angle of entrainment. The aim was to explore if behavioural rhythms, in addition to the biological circadian rhythms contribute to misalignments of sleep timing symptomatic of DSWPD and N24SWD. Twenty-six DSWPD participants who met diagnostic criteria (17m, 9f, age: 21.85 ± 4.97 years) and 18 controls (10m, 8f, age: 23.72 ± 5.10 years) participated in an 80-hour modified constant routine. Additionally, 4 full-sighted patients (3m, 1f, age: 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. A forced-desynchrony ultradian protocol of 1-hour ‘days’ in dim light, controlled conditions alternated 20-minute sleep opportunities with 40-minute enforced wakefulness. Subjective sleepiness ratings were recorded prior to every sleep opportunity and median reaction time (vigilance) was measured hourly. Amount of sleep obtained (sleep propensity) was derived from 20-minute sleep opportunities to quantify hourly objective sleepiness. Hourly core body temperature was recorded and salivary melatonin assayed to measure endogenous circadian rhythms. Rhythm data were curved using the 2-component cosine model. DSWPD and N24SWD patients had significantly longer melatonin and temperature taus compared to controls. There were no significant tau differences between groups as measured by subjective sleepiness, sleep propensity and vigilance rhythms. However, DSWPD patients showed a greater interval between maximum sleep propensity and minimum core body temperature. Their sleep propensity rhythms lagged core temperature rhythms by an hour more compared to controls’ sleep propensity and core temperature rhythms. The findings provide further evidence that delayed circadian rhythms in DSWPD may result from larger phase angles between core body temperature and sleep propensity. This interval may result in later sleep timing in DSWPD patients relative to their circadian timing thus masking their light exposure during a time that is critical to phase-advancing the circadian system. This project was funded by the Australian Research Council.

Evaluation of circadian phenotypes utilizing fibroblasts from patients with circadian rhythm sleep disorders

We evaluated the circadian phenotypes of patients with delayed sleep–wake phase disorder (DSWPD) and non-24-hour sleep–wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22.80±0.47 (mean±s.d.) h in control-derived fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived fibroblasts were 22.67±0.67 h and 23.18±0.70 h, respectively. The N24SWD group showed a significantly longer in vitro period than did the control or DSWPD group. Furthermore, in vitro period was associated with response to chronotherapy in the N24SWD group. Longer in vitro periods were observed in the non-responders (mean±s.d.: 23.59±0.89 h) compared with the responders (mean±s.d.: 22.97±0.47 h) in the N24SWD group. Our results indicate that prolonged circadian periods contribute to the onset and poor treatment outcome of N24SWD. In vitro rhythm assays could be useful for predicting circadian phenotypes and clinical prognosis in patients with CRSDs.

Can dim light melatonin onset be predicted by the timing of sleep in patients with possible circadian sleep-wake rhythm disorders?

Dim Light Melatonin Onset (DLMO) is a reliable marker of the endogenous circadian rhythm. To determine if sleep timing can predict DLMO, we investigated the relationship between sleep timing and DLMO in patients in various circadian sleep-wake rhythm disorders (CSWRDs), ages and genders. We found that correlations were only moderate between DLMO and sleep-onset in the complete data-set, but they increased in patients with delayed sleep-wake phase disorder (DSWPD), DSWPD patients with a regular sleep pattern and patients with advanced sleep-wake phase disorder (ASWPD); the levels of correlation were r = 0.542, 0.657, 0.728 and 0.814, respectively. In DSWPD patients with a regular sleep pattern, mid-sleep strongly correlated (r = 0.839) with DLMO. Correlation in other CSRWDs was not significant. DLMO, sleep-onset and age were most discriminated factors between the various CSRWDs. Estimation of DLMO is only possible in patients with ASWPD and in DSWPD patients with a regular sleep pattern.

Examining the Behavioural Sleep-Wake Rhythm in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability

This study aimed to examine the behavioural sleep-wake rhythm in 36 adults with autism spectrum disorder (ASD) and to determine the prevalence of circadian sleep-wake rhythm disorders compared to age- and sex-matched controls. Participants completed an online questionnaire battery, a 14-day sleep-wake diary and 14-day actigraphy assessment. The results indicated that a higher proportion of adults with ASD met criteria for a circadian rhythm sleep-wake disorder compared to control adults. In particular, delayed sleep-wake phase disorder was particularly common in adults with ASD. Overall the findings suggest that individuals with ASD have sleep patterns that may be associated with circadian rhythm disturbance; however factors such as employment status and co-morbid anxiety and depression appear to influence their sleep patterns.

Pathophysiology and strategic treatment of sighted non-24-h sleep–wake rhythm disorders

Non-24-h sleep–wake rhythm disorder (N24SWD) is one type of circadian rhythm sleep–wake disorder. Once developed, N24SWD causes occupational and social dysfunction due to its early onset, long-term morbidity, and intractable nature, imposing a huge burden on individuals with the disorder. N24SWD is highly prevalent in blind individuals who have had no photic entrainment. The pathophysiology of sighted N24SWD in individuals with no visual impairment is unclear, but as a concept, impaired entrainment to the 24-h day–night cycle or abnormality in the free-running period (τ) was thought to be the cause of N24SWD. A recent study using a strict forced desynchrony protocol revealed prolonged τ in sighted N24SWD patients. In contrast, some evening chronotypes are able to entrain to the 24-h-day cycle despite having similarly prolonged τ. Therefore, the onset of N24SWD could be reasonably explained by the multiple-hit hypothesis, which proposes that disease onset requires the coexistence of multiple vulnerabilities, such as prolonged τ, abnormal photosensitivity, overexposure to ambient light in the delay zone of the phase response curve, and psychiatric problems. The application of a molecular genetic approach similar to that used in the study of advanced sleep–wake phase disorder is difficult because of the absence of familial occurrence in most sighted N24SWD patients. However, a different experimental approach such as whole-exome analysis of individual cases may be useful for clarifying the molecular basis underlying the onset of sighted N24SWD.

Circadian Melatonin and Temperature Taus in Delayed Sleep-wake Phase Disorder and Non-24-hour Sleep-wake Rhythm Disorder Patients: An Ultradian Constant Routine Study.

Our objectives were to investigate the period lengths (i.e., taus) of the endogenous core body temperature rhythm and melatonin rhythm in delayed sleep-wake phase disorder patients (DSWPD) and non-24-h sleep-wake rhythm disorder patients (N24SWD) compared with normally entrained individuals. Circadian rhythms were measured during an 80-h ultradian modified constant routine consisting of 80 ultrashort 1-h "days" in which participants had 20-min sleep opportunities alternating with 40 min of enforced wakefulness. We recruited a community-based sample of 26 DSWPD patients who met diagnostic criteria (17 males, 9 females; age, 21.85 ± 4.97 years) and 18 healthy controls (10 males, 8 females; age, 23.72 ± 5.10 years). Additionally, 4 full-sighted patients (3 males, 1 female; age, 25.75 ± 4.99 years) were diagnosed with N24SWD and included as a discrete study group. Ingestible core temperature capsules were used to record minute temperatures that were averaged to obtain 80 hourly data points. Salivary melatonin concentration was assessed every half-hour to determine time of dim light melatonin onset at the beginning and end of the 80-h protocol. DSWPD patients had significantly longer melatonin rhythm taus (24 h 34 min ± 17 min) than controls (24 h 22 min ± 15 min, p = 0.03, d = 0.70). These results were further supported by longer temperature rhythm taus in DSWPD patients (24 h 34 min ± 26 min) relative to controls (24 h 13 min ± 15 min, p = 0.01, d = 0.80). N24SWD patients had even longer melatonin (25 h ± 19 min) and temperature (24 h 52 min ± 17 min) taus than both DSWPD (p = 0.007, p = 0.06) and control participants (p < 0.001, p = 0.02, respectively). Between 12% and 19% of the variance in DSWPD patients' sleep timing could be explained by longer taus. This indicates that longer taus of circadian rhythms may contribute to the DSWPD patients' persistent tendency to delay, their frequent failure to respond to treatment, and their relapse following treatment. Additionally, other factors can contribute to misalignments in DSWPD and N24SWD disorders.

A Pre-Screening Questionnaire to Predict Non-24-Hour Sleep-Wake Rhythm Disorder (N24HSWD) among the Blind.

There is currently no questionnaire-based pre-screening tool available to detect non-24-hour sleep-wake rhythm disorder (N24HSWD) among blind patients. Our goal was to develop such a tool, derived from gold standard, objective hormonal measures of circadian entrainment status, for the detection of N24HSWD among those with visual impairment. We evaluated the contribution of 40 variables in their ability to predict N24HSWD among 127 blind women, classified using urinary 6-sulfatoxymelatonin period, an objective marker of circadian entrainment status in this population. We subjected the 40 candidate predictors to 1,000 bootstrapped iterations of a logistic regression forward selection model to predict N24HSWD, with model inclusion set at the p < 0.05 level. We removed any predictors that were not selected at least 1% of the time in the 1,000 bootstrapped models and applied a second round of 1,000 bootstrapped logistic regression forward selection models to the remaining 23 candidate predictors. We included all questions that were selected at least 10% of the time in the final model. We subjected the selected predictors to a final logistic regression model to predict N24SWD over 1,000 bootstrapped models to calculate the concordance statistic and adjusted optimism of the final model. We used this information to generate a predictive model and determined the sensitivity and specificity of the model. Finally, we applied the model to a cohort of 1,262 blind women who completed the survey, but did not collect urine samples. The final model consisted of eight questions. The concordance statistic, adjusted for bootstrapping, was 0.85. The positive predictive value was 88%, the negative predictive value was 79%. Applying this model to our larger dataset of women, we found that 61% of those without light perception, and 27% with some degree of light perception, would be referred for further screening for N24HSWD. Our model has predictive utility sufficient to serve as a pre-screening questionnaire for N24HSWD among the blind.

Personality differences in patients with delayed sleep–wake phase disorder and non-24-h sleep–wake rhythm disorder relative to healthy sleepers

Objective/BackgroundDelayed sleep–wake phase disorder (DSWPD) is associated with a delayed timing of circadian rhythms, and this delay is suggested to be the basis of the disorder. However, this has been questioned due to frequent relapses following treatment based on this aetiology. Recent studies have emerged suggesting personality factors may contribute to sleep patterns in DSWPD. The aim of this study was to further investigate circadian and personality factors in DSWPD patients as well as patients with non-24-h sleep–wake rhythm disorder (N24SWD) relative to control sleepers. Patients/MethodsThis sample consisted of 16 DSWPD (age = 21.1 ± 2.8, 10 m, 7 f), and three N24SWD patients (age = 24.0 ± 4.4, 2 m, 1 f). Controls were seven males and seven females (age = 23.4 ± 5.9). Before starting an 80-h modified constant routine, eligible participants’ sleep patterns were monitored for a week and they completed a personality questionnaire (NEO PI–R). An ultradian routine with alternating 20-min sleep opportunities and 40 min of enforced wakefulness was used to measure the timing of endogenous circadian temperature and melatonin rhythms. ResultsAs compared with controls, DSWPD patients reported higher neuroticism, significantly lower extraversion, conscientiousness and agreeableness. Similarly, N24SWD patients’ patterns of personality traits were similar to that of DSWPD. Conscientiousness, in particular, was associated with phase timings of circadian rhythms as well as sleep measures and lifestyle factors within the DSWPD group. ConclusionsThese findings suggest that circadian rhythm sleep–wake disorders (CRSWDs) may not only stem from circadian abnormalities but personality factors may also drive lifestyle choices, including sleep timing.