The circadian rhythm for mood (CRM) is a digital therapeutic, which aims to prevent mood episode and improve clinical course in patients with major mood disorders. Developed on the circadian rhythm hypothesis of mood disorder, CRM predicts the impending risk of mood episode with its built-in algorithm, utilizing wearable devices data and daily self-reports, and provides personalized feedback. In a pilot study of the CRM, the users experienced less frequent and shorter duration of mood episodes than the non-users. To investigate the efficacy of the upgraded CRM, a double-blind, randomized, sham-controlled, parallel-group trial is designed. Patients aged between 19 and 70, diagnosed with bipolar I disorder, bipolar II disorder, or major depressive disorder, in a euthymic state for more than two months, can participate. During this 12-month trial, participants are assessed for episode recurrence every three months, and the efficacy of the CRM as a potential digital therapeutic is evaluated. Trial registration: ClinicalTrials.gov Identifier: NCT05400785.

Preoperative anaemia is common in the Asia-Pacific. Iron deficiency anaemia (IDA) is a risk factor that can be addressed under patient blood management (PBM) Pillar 1, leading to reduced morbidity and mortality. We examined PBM implementation under four different healthcare systems, identified challenges and proposed several measures: (a) Test for anaemia once patients are scheduled for surgery. (b) Inform patients about risks of preoperative anaemia and benefits of treatment. (c) Treat IDA and replenish iron stores before surgery, using intravenous iron when oral treatment is ineffective, not tolerated or when rapid iron replenishment is needed; transfusion should not be the default management. (d) Harness support from multiple medical disciplines and relevant bodies to promote PBM implementation. (e) Demonstrate better outcomes and cost savings from reduced mortality and morbidity. Although PBM implementation may seem complex and daunting, it is feasible to start small. Implementing PBM Pillar 1, particularly in preoperative patients, is a sensible first step regardless of the healthcare setting.

OBJECTIVE: The Epworth Sleepiness Scale is a measure used for the diagnosis of sleep disorders including obstructive sleep apnea (OSA) syndrome, insomnia, and narcolepsy. Although a Korean version has been developed (the KESS), Korean lifestyle such as the floor culture and low driving rates has not been considered. We aim to develop and validate a modified KESS (mKESS) that reflects the Korean lifestyle. METHODS: The sample consisted of 795 healthy participants and 323 OSA patients. The mKESS was developed by modifying several questions to concern the floor culture (questions 1, 2, 6, and 7) and low driving rates (question 8). Feasibility of the modification was tested by comparing the KESS and mKESS using paired samples t-test and by examining internal consistency reliability. Then, mKESS scores of the OSA patients and general participants were compared to test its validity. RESULTS: Questions 1, 2, 7, and 8 were significantly different when comparing the performances of the general population on both scales. Especially, the mean scores on question 8 were significantly different in the non-driver group, but not in the driver group. Cronbach’s alpha of the mKESS was relatively higher than that of the KESS. Total mKESS scores of the OSA patients were significantly higher than that of the general population. CONCLUSION: The mKESS is more universally applicable for the clinical evaluation of people that live in Korea. Results support that the mKESS can be administered to measure the average daytime sleep propensity of the Korean population as an alternative to the KESS.
Diagnosis ; Healthy Volunteers ; Humans ; Korea ; Life Style* ; Narcolepsy ; Sleep Apnea, Obstructive ; Sleep Initiation and Maintenance Disorders ; Sleep Wake Disorders ; Weights and Measures

OBJECTIVE: Light pollution has become a social and health issue. We performed an experimental study to investigate impact of dim light at night (dLAN) on sleep in female subjects, with measurement of salivary melatonin. METHODS: The 25 female subjects (Group A: 12; Group B: 13 subjects) underwent a nocturnal polysomnography (NPSG) session with no light (Night 1) followed by an NPSG session randomly assigned to two conditions (Group A: 5; Group B: 10 lux) during a whole night of sleep (Night 2). Salivary melatonin was measured before and after sleep on each night. For further investigation, the female and male subjects of our previous study were collected (48 subjects), and differences according to gender were compared. RESULTS: dLAN during sleep was significantly associated with decreased total sleep time (TST; F=4.818, p=0.039), sleep efficiency (SE; F=5.072, p=0.034), and Stage R latency (F=4.664, p=0.041) for female subjects, and decreased TST (F=14.971, p<0.001) and SE (F=7.687, p=0.008), and increased wake time after sleep onset (F=6.322, p=0.015) and Stage R (F=5.031, p=0.03), with a night-group interaction (F=4.579, p=0.038) for total sample. However, no significant melatonin changes. There was no significant gender difference of the impact of dLAN on sleep, showing the negative changes in the amount and quality of sleep and the increase in rapid eye movement (REM) sleep in the both gender group under 10 lux condition. CONCLUSION: We found a negative impact of exposure to dLAN on sleep in female as well as in merged subjects. REM sleep showed a pronounced increase under 10 lux than under 5 lux in merged subjects, suggesting the possibility of subtle influences of dLAN on REM sleep.
Female* ; Humans ; Male* ; Melatonin ; Polysomnography ; Sleep, REM

OBJECTIVE: Restless legs syndrome (RLS) is considered a genetic disease and, following a genome-wide association study conducted in 2007, the mitogen-activated protein kinase 5 (MAP2K5) gene has been regarded as the promising candidate gene for RLS. The present study investigated whether polymorphisms of MAP2K5 are associated with antipsychotics-induced RLS in schizophrenia. METHODS: We assessed antipsychotics-induced RLS symptoms in 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group. Five single-nucleotide polymorphisms (SNPs) of MAP2K5 were genotyped. We investigated genetic and haplotypic associations of these five SNPs with the risk of antipsychotics-induced RLS symptoms. RESULTS: We divided the 190 subjects into 2 groups: 1) those with RLS symptoms (n=96) and 2) those without RLS symptoms (n=94). There were no significant intergroup differences in the distributions of the genotypes and alleles of the rs1026732, rs11635424, rs12593813, rs4489954, and rs3784709 SNPs. However, the haplotype analysis showed that the G-G-G-G-T (rs1026732-rs11635424-rs12593813-rs4489954-rs3784709) haplotype was associated with RLS symptoms (permutation p=0.033). CONCLUSION: These data suggest that a haplotype of MAP2K5 polymorphisms confers increased susceptibility to antipsychotics-induced RLS symptoms in schizophrenic patients.
Alleles ; Antipsychotic Agents ; Genome-Wide Association Study ; Genotype ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; Protein Kinases ; Restless Legs Syndrome ; Schizophrenia

OBJECTIVE: Seasonal affective disorder and seasonal changes in mood and behavior are associated with several genes that regulate circadian rhythms. In this study, we investigated the relationship between the C825T polymorphism of the G-protein β3 subunit and seasonal variations in mood and behavior in a young healthy Korean population. METHODS: A total of 507 young Korean participants were recruited through a newspaper advertisement, and their seasonality was evaluated by the Korean version of the Seasonal Pattern Assessment Questionnaire to assess the global seasonality score (GSS). We analyzed the CC, CT, and TT genotypes and their association with the GSS score and subscales. RESULTS: T allele carriers of the GNB3 C825T polymorphism were more likely to score higher on body weight and GSS. In the female group, the T allele carriers obtained significantly high total GSS and its subscale scores for mood, body weight, energy level, and appetite; however, differences in genotypes and allele carriers were also observed in the male participants. CONCLUSION: These results suggested that GNB3 C825T polymorphism plays a role in seasonal variations in mood, body weight, energy level, and appetite in a Korean population, particularly in females.
Alleles ; Appetite ; Body Weight ; Circadian Rhythm ; Female ; Genotype ; GTP-Binding Proteins ; Humans ; Male ; Seasonal Affective Disorder ; Seasons

OBJECTIVE: The purpose of this study was to evaluate the applicability of data obtained from a wearable activity tracker (Fitbit Charge HR) to medical research. This was performed by comparing the wearable activity tracker (Fitbit Charge HR) with actigraphy (Actiwatch 2) for sleep evaluation and circadian rest-activity rhythm measurement. METHODS: Sixteen healthy young adults (female participants, 62.5%; mean age, 22.8 years) wore the Fitbit Charge HR and the Actiwatch 2 on the same wrist; a sleep log was recorded over a 14-day period. We compared the sleep variables and circadian rest-activity rhythm measures with Wilcoxon signed-rank tests and Spearman's correlations. RESULTS: The periods and acrophases of the circadian rest-activity rhythms and the sleep start times did not differ and correlated significantly between the Fitbit Charge HR and the Actiwatch 2. The Fitbit Charge HR tended to overestimate the sleep durations compared with the Actiwatch 2. However, the sleep durations showed high correlation between the two devices for all days. CONCLUSION: We found that the Fitbit Charge HR showed high accuracy in sleep evaluation and circadian rest-activity rhythm measurement when compared with actigraphy for healthy young adults. The results suggest that the Fitbit Charge HR could be applicable on medical research as an alternative tool to actigraphy for sleep evaluation and measurement of the circadian rest-activity rhythm.
Actigraphy* ; Humans ; Wrist ; Young Adult*

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10−6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10−6) and rs9390170 (OR=0.6778, p=7.67×10−6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10−18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.
Epidemiology ; Genetic Markers ; Genome ; Genome-Wide Association Study* ; Haplotypes ; Korea ; Restless Legs Syndrome* ; Synapses ; Utrophin

Restless legs syndrome (RLS) is a sensorimotor neurological disturbance causing physical and psychological distress. Here, we investigated the severity and effect of depressive symptoms in RLS among a Korean cohort population. Depressive symptoms were more prevalent in the RLS group than in the non-RLS group [≥mild depression: odds ratio (OR)=1.95, p < 0.001; ≥ moderate depression: OR=6.15, p < 0.001; and ≥severe depression: OR=56.54, p < 0.001], with a predominant proportion of severe depression (97%) in the RLS group. We found that difficulty falling asleep (OR=8.16, p < 0.001), broken sleep (OR=11.66, p=0.001), early morning awakening (OR=8.5, p < 0.001), and excessive daytime sleepiness (OR=3.04, p=0.031) were significantly frequent in individuals with severe depression in the RLS group. Red blood cell count was significantly low in individuals with severe depression in the RLS group (p=0.041). We found that severe depression was associated with RLS, suggesting the evaluation and management of mood symptoms and sleep-related and hematological features when treating RLS.
Accidental Falls ; Cohort Studies* ; Depression* ; Erythrocyte Count ; Odds Ratio ; Restless Legs Syndrome* ; Sleep Initiation and Maintenance Disorders

OBJECTIVES: Exposure to light at night has become pervasive in modern society. The impact of dim artificial light at night (dALAN) exposure on sleep and fatigue is not well recognized. We aim to study the impact of dALAN exposure during sleep on human fatigue. METHODS: 30 healthy young male volunteers from 21 to 29 years old were enrolled in the study. They were randomly divided into two groups depending on light intensity (Group A : 5 lux and Group B : 10 lux). Data were gathered from each participant after each night with no light (Night 1) followed by the next night (Night 2) with two different dim light conditions (5 or 10 lux) by means of self-reported fatigue scale. RESULTS: Exposure to dALAN during sleep was significantly associated with increased overall fatigue (F = 19.556, p < 0.001) and ocular discomfort (F = 5.671, p = 0.028). CONCLUSION: We found that dALAN during sleep likely affects human fatigue in some aspects. These findings indicate that dALAN during sleep exerts a negative effect on human fatigue.
Fatigue* ; Humans* ; Male ; Volunteers