Prediction of impending mood episode recurrence using real-time digital phenotypes in major depression and bipolar disorders in South Korea: a prospective nationwide cohort study.

BACKGROUND: Mood disorders require consistent management of symptoms to prevent recurrences of mood episodes. Circadian rhythm (CR) disruption is a key symptom of mood disorders to be proactively managed to prevent mood episode recurrences. This study aims to predict impending mood episodes recurrences using digital phenotypes related to CR obtained from wearable devices and smartphones. METHODS: The study is a multicenter, nationwide, prospective, observational study with major depressive disorder, bipolar disorder I, and bipolar II disorder. A total of 495 patients were recruited from eight hospitals in South Korea. Patients were followed up for an average of 279.7 days (a total sample of 75 506 days) with wearable devices and smartphones and with clinical interviews conducted every 3 months. Algorithms predicting impending mood episodes were developed with machine learning. Algorithm-predicted mood episodes were then compared to those identified through face-to-face clinical interviews incorporating ecological momentary assessments of daily mood and energy. RESULTS: Two hundred seventy mood episodes recurred in 135 subjects during the follow-up period. The prediction accuracies for impending major depressive episodes, manic episodes, and hypomanic episodes for the next 3 days were 90.1, 92.6, and 93.0%, with the area under the curve values of 0.937, 0.957, and 0.963, respectively. CONCLUSIONS: We predicted the onset of mood episode recurrences exclusively using digital phenotypes. Specifically, phenotypes indicating CR misalignment contributed the most to the prediction of episodes recurrences. Our findings suggest that monitoring of CR using digital devices can be useful in preventing and treating mood disorders.

Effectiveness of a Smartphone App With a Wearable Activity Tracker in Preventing the Recurrence of Mood Disorders: Prospective Case-Control Study.

BACKGROUND: Smartphones and wearable devices can be used to obtain diverse daily log data related to circadian rhythms. For patients with mood disorders, giving feedback via a smartphone app with appropriate behavioral correction guides could play an important therapeutic role in the real world. OBJECTIVE: We aimed to evaluate the effectiveness of a smartphone app named Circadian Rhythm for Mood (CRM), which was developed to prevent mood episodes based on a machine learning algorithm that uses passive digital phenotype data of circadian rhythm behaviors obtained with a wearable activity tracker. The feedback intervention for the CRM app consisted of a trend report of mood prediction, H-score feedback with behavioral guidance, and an alert system triggered when trending toward a high-risk state. METHODS: In total, 73 patients with a major mood disorder were recruited and allocated in a nonrandomized fashion into 2 groups: the CRM group (14 patients) and the non-CRM group (59 patients). After the data qualification process, 10 subjects in the CRM group and 33 subjects in the non-CRM group were evaluated over 12 months. Both groups were treated in a similar manner. Patients took their usual medications, wore a wrist-worn activity tracker, and checked their eMoodChart daily. Patients in the CRM group were provided with daily feedback on their mood prediction and health scores based on the algorithm. For the CRM group, warning alerts were given when irregular life patterns were observed. However, these alerts were not given to patients in the non-CRM group. Every 3 months, mood episodes that had occurred in the previous 3 months were assessed based on the completed daily eMoodChart for both groups. The clinical course and prognosis, including mood episodes, were evaluated via face-to-face interviews based on the completed daily eMoodChart. For a 1-year prospective period, the number and duration of mood episodes were compared between the CRM and non-CRM groups using a generalized linear model. RESULTS: The CRM group had 96.7% fewer total depressive episodes (n/year; exp ß=0.033, P=.03), 99.5% shorter depressive episodes (total; exp ß=0.005, P<.001), 96.1% shorter manic or hypomanic episodes (exp ß=0.039, P<.001), 97.4% fewer total mood episodes (exp ß=0.026, P=.008), and 98.9% shorter mood episodes (total; exp ß=0.011, P<.001) than the non-CRM group. Positive changes in health behaviors due to the alerts and in wearable device adherence rates were observed in the CRM group. CONCLUSIONS: The CRM app with a wearable activity tracker was found to be effective in preventing and reducing the recurrence of mood disorders, improving prognosis, and promoting better health behaviors. Patients appeared to develop a regular habit of using the CRM app. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088657; https://clinicaltrials.gov/ct2/show/NCT03088657.

Temporal association between zolpidem medication and the risk of suicide: A 12-year population-based, retrospective cohort study.

There have been concerns about abuse and unnecessary chronic administration of zolpidem, and zolpidem's relation to suicide risk. To investigate the temporal association of zolpidem with the risk of suicide, we conducted a 12-year, population-based, retrospective cohort study on the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Data were collected from 2002 to 2013 from the NHIS-NSC, and data cleaning was performed for 1,125,691 subjects. Cox proportional hazards regression analysis was used to investigate the correlation over time between zolpidem medication and suicide. Over intervals commencing after 80 months of observation, the adjusted hazard ratio of suicides associated with the use of the zolpidem was 2.01 (95% CI: 1.58-2.56; p < 0.001). The mean cumulative number of days of zolpidem prescription was significantly longer in the suicide group than in the non-suicide group after log-transformation (p = 0.005). Cases of chronic use of zolpidem (over six months or one year) were significantly more common in the suicide group compared to the non-suicide group (p = 0.002 and 0.005, respectively). Subjects who received zolpidem medication had a significantly higher risk of suicide after at least 80 months of observation, suggesting a long-term increased suicide risk associated with insomnia exposed to zolpidem medication.

Association between weekend catch-up sleep and high-sensitivity C-reactive protein levels in adults: a population-based study.

STUDY OBJECTIVES: To investigate the association between weekend catch-up sleep (WCS) and the levels of high-sensitivity C-reactive protein (hsCRP)-a serum inflammatory maker-in adults. METHODS: Data of 5,506 adults aged 19 years or older were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys conducted in 2016. Serum hsCRP level, weekday and weekend sleep durations, and sociodemographic and health-related characteristics were assessed. Participants whose weekend sleep duration was more than 1 h longer than their weekday sleep duration were included in the WCS group. hsCRP level was categorized into quartiles (i.e. highest, middle-high, middle-low, and lowest). Obesity was defined by body mass index ≥ 25.0 kg/m2. RESULTS: The WCS group included 1,901 participants (34.5%). In the logistic regression analysis controlling for all variables, adults in the WCS group were significantly less likely to show the highest hsCRP level (versus the lowest level) compared with those without WCS in the complete sample (adjusted odds ratio = 0.795, 95% confidence interval [CI] = 0.662 to 0.955). In a subgroup analysis, this association was significant only for those with weekday sleep duration of 6 h or lower. Longer WCS (≥3 h) was not associated with hsCRP levels. Non-obese people with WCS demonstrated a lower risk for high hsCRP levels, while there was no significant difference in obese people with WCS. CONCLUSIONS: Our findings indicate that WCS may be beneficial for low-grade systemic inflammation in adults, particularly among those with shorter weekday sleep durations. WCS may also interact with obesity.

Addendum to the Acknowledgements: Mood Prediction of Patients With Mood Disorders by Machine Learning Using Passive Digital Phenotypes Based on the Circadian Rhythm: Prospective Observational Cohort Study.

[This corrects the article DOI: 10.2196/11029.].

Mood Prediction of Patients With Mood Disorders by Machine Learning Using Passive Digital Phenotypes Based on the Circadian Rhythm: Prospective Observational Cohort Study.

BACKGROUND: Virtually, all organisms on Earth have their own circadian rhythm, and humans are no exception. Circadian rhythms are associated with various human states, especially mood disorders, and disturbance of the circadian rhythm is known to be very closely related. Attempts have also been made to derive clinical implications associated with mood disorders using the vast amounts of digital log that is acquired by digital technologies develop and using computational analysis techniques. OBJECTIVE: This study was conducted to evaluate the mood state or episode, activity, sleep, light exposure, and heart rate during a period of about 2 years by acquiring various digital log data through wearable devices and smartphone apps as well as conventional clinical assessments. We investigated a mood prediction algorithm developed with machine learning using passive data phenotypes based on circadian rhythms. METHODS: We performed a prospective observational cohort study on 55 patients with mood disorders (major depressive disorder [MDD] and bipolar disorder type 1 [BD I] and 2 [BD II]) for 2 years. A smartphone app for self-recording daily mood scores and detecting light exposure (using the installed sensor) were provided. From daily worn activity trackers, digital log data of activity, sleep, and heart rate were collected. Passive digital phenotypes were processed into 130 features based on circadian rhythms, and a mood prediction algorithm was developed by random forest. RESULTS: The mood state prediction accuracies for the next 3 days in all patients, MDD patients, BD I patients, and BD II patients were 65%, 65%, 64%, and 65% with 0.7, 0.69, 0.67, and 0.67 area under the curve (AUC) values, respectively. The accuracies of all patients for no episode (NE), depressive episode (DE), manic episode (ME), and hypomanic episode (HME) were 85.3%, 87%, 94%, and 91.2% with 0.87, 0.87, 0.958, and 0.912 AUC values, respectively. The prediction accuracy in BD II patients was distinctively balanced as high showing 82.6%, 74.4%, and 87.5% of accuracy (with generally good sensitivity and specificity) with 0.919, 0.868, and 0.949 AUC values for NE, DE, and HME, respectively. CONCLUSIONS: On the basis of the theoretical basis of chronobiology, this study proposed a good model for future research by developing a mood prediction algorithm using machine learning by processing and reclassifying digital log data. In addition to academic value, it is expected that this study will be of practical help to improve the prognosis of patients with mood disorders by making it possible to apply actual clinical application owing to the rapid expansion of digital technology.

Development of a Modified Korean Version of the Epworth Sleepiness Scale Reflecting Korean Sociocultural Lifestyle.

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.

Impact of Exposure to Dim Light at Night on Sleep in Female and Comparison with Male Subjects.

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 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.

Haplotype Association of the MAP2K5 Gene with Antipsychotics-Induced Symptoms of Restless Legs Syndrome among Patients with Schizophrenia.

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.

Association of G-Protein ß3 Subunit C825T Polymorphism with Seasonal Variations in Mood and Behavior.

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 ß3 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.

A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population.

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.

Individuals with Restless Legs Syndrome Tend to have Severe Depressive Symptoms: Findings from a Community-Based Cohort Study.

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.

Correlation of occupational stress with depression, anxiety, and sleep in Korean dentists: cross-sectional study.

BACKGROUND: This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea. METHODS: A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis. RESULTS: The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t = 3.93, P < 0.0001; t = 4.05, P < 0.0001; t = 4.18, P < 0.0001, respectively). In particular, patient factors and clinical responsibility/judgment factors were significantly associated with depression (t = 2.80, P = 0.0056; t = 4.93, P < 0.0001, respectively), anxiety (t = 2.35, P = 0.0195; t = 5.11, P < 0.0001, respectively), and sleep (t = 3.78, P = 0.0002; t = 4.30, P < 0.0001, respectively), whereas work factors were not associated with any mental health state. CONCLUSIONS: This study confirms that dentists as professions experience more severe mental states. For successful mental health care among dentists, stress management focusing on interpersonal relationship with patients and responsibility as an expert rather than the intensity of work should be considered.

Comparison of Wearable Activity Tracker with Actigraphy for Sleep Evaluation and Circadian Rest-Activity Rhythm Measurement in Healthy Young Adults.

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.

Cognitive Behavioral Therapy Using a Mobile Application Synchronizable With Wearable Devices for Insomnia Treatment: A Pilot Study.

STUDY OBJECTIVES: The use of telemedicine with a mobile application (MA) and a wearable device (WD) for the management of sleep disorders has recently received considerable attention. We designed an MA synchronizable with a WD for insomnia treatment. Our pilot study determined the efficacy of simplified group cognitive behavioral therapy for insomnia (CBT-I) delivered using our MA and assessed participant adherence to and satisfaction with the device. METHODS: The efficacy of the CBT-I using MA (CBT-I-MA) was assessed by comparing sleep variables (sleep efficiency [SE], Insomnia Severity Index [ISI], and Pittsburgh Sleep Quality Inventory [PSQI] scores) before and after a 4-week treatment protocol in 19 patients with insomnia disorder patients. SE was assessed using a sleep diary, actigraphy, and the PSQI. RESULTS: The intervention significantly improved all three measures of SE (P < .05), and the response rate to treatment was high (94.7%). Total ISI and PSQI scores and sleep latency, as measured by the sleep diary, improved significantly. Participants showed relatively good adherence to our MA, and sleep diary entries were made on 24.3 ± 3.8 of 28 days. Moreover, 94.7% of the participants reported that our MA was effective for treating insomnia. CONCLUSIONS: Our pilot study suggested the clinical usefulness of a CBT-I-MA. We expect that our findings will lead to further development and replication studies of CBT-I-MA.

Decrease in fMRI brain activation during working memory performed after sleeping under 10 lux light.

The aim of this study was to investigate the effect of exposure to dim light at night (dLAN) when sleeping on functional brain activation during a working-memory tasks. We conducted the brain functional magnetic resonance imaging (fMRI) analysis on 20 healthy male subjects. All participants slept in a polysomnography laboratory without light exposure on the first and second nights and under a dim-light condition of either 5 or 10 lux on the third night. The fMRI scanning was conducted during n-back tasks after second and third nights. Statistical parametric maps revealed less activation in the right inferior frontal gyrus (IFG) after exposure to 10-lux light. The brain activity in the right and left IFG areas decreased more during the 2-back task than during the 1- or 0-back task in the 10-lux group. The exposure to 5-lux light had no significant effect on brain activities. The exposure to dLAN might influence the brain function which is related to the cognition.

Association of CLOCK, ARNTL, PER2, and GNB3 polymorphisms with diurnal preference in a Korean population.

Polymorphisms in human circadian genes are potential genetic markers that affect diurnal preference in several populations. In this study, we evaluated whether four polymorphisms in circadian genes CLOCK, ARNTL, PER2, and GNB3 were associated with diurnal preference in a Korean population. In all, 499 healthy subjects were genotyped for four functional polymorphisms in CLOCK, ARNTL, PER2, and GNB3. Composite scale of morningness (CSM) was applied to measure phenotype patterns of human diurnal preference. In addition, three subscale scores, i.e. "morningness," "activity planning," and "morning alertness," were extracted from the CSM. No significant associations were observed between CSM scores and CLOCK (rs1801260) genotype or T allele carrier status, CSM scores and ARNTL (rs2278749) C allele carrier status, and CSM scores and GNB3 (rs5443) genotype or C allele carrier status. However, total CSM scores and scores of its subscales were significantly associated with PER2 (rs934945) genotype (p = 0.010, p = 0.018, and p = 0.005 for total, morningness, and activity planning, respectively) and G allele carrier status (p = 0.003, p = 0.005, and p = 0.002 for total, morningness, and activity planning, respectively). The best model result obtained by performing multifactor dimensionality reduction analysis ([Formula: see text]2 = 11.2798, p = 0.0008) indicated that interaction among C/T single nucleotide polymorphism (SNP) in ARNTL, C/T SNP in GNB3, and G/A SNP in PER2 synergistically affected the risk associated with diurnal preference toward eveningness. These results suggest that circadian gene PER2 is associated with diurnal preference in healthy Korean population. Although polymorphisms in ARNTL and GNB3 were not significantly associated with diurnal preference, their interactions with the polymorphism in PER2 may synergistically increase the risk of diurnal preference toward eveningness.

Advanced Circadian Phase in Mania and Delayed Circadian Phase in Mixed Mania and Depression Returned to Normal after Treatment of Bipolar Disorder.

Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7hour advanced (equivalent to ~17hour delayed). Phases of 21 out of these 23 cases returned to normal by ~7hour delay along with treatment, but two out of 23 cases returned to normal by ~17hour advance. In three cases of mixed manic episodes, the phases were ~6-7hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~4-5hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD.

Molecular circadian rhythm shift due to bright light exposure before bedtime is related to subthreshold bipolarity.

This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way. Molecular circadian rhythms were analyzed using sine regression. Circadian rhythms of cortisol (F = 16.956, p < 0.001) and relative PER1/ARNTL gene expression (F = 122.1, p < 0.001) showed a delayed acrophase in both groups after bright light exposure. The high MDQ score group showed a significant delay in acrophase compared to the low MDQ score group only in salivary cortisol (F = 8.528, p = 0.008). The high MDQ score group showed hypersensitivity in cortisol rhythm shift after bright light exposure, suggesting characteristic molecular circadian rhythm changes in the high MDQ score group may be related to biological processes downstream from core circadian clock gene expression.

Sleep Irregularity in the Previous Week Influences the First-Night Effect in Polysomnographic Studies.

OBJECTIVE: The first-night effect is a well-known phenomenon resulting from an individual's maladaptation to the unfamiliar environment of a sleep laboratory. However, there have been no direct reports of the effect of previous sleep patterns on the first-night effect. We aimed to investigate the effect the previous week's sleep pattern on the first-night effect. METHODS: Twenty-four young, healthy, male participants completed the study procedure. During one week prior to study, the participants kept sleep diaries and wore actigraphs to identify sleep-wake pattern. Two consecutive nights of polysomnography were conducted after that. Wilcoxon signed-rank tests were applied to compare sleep variables of the two nights. Variance (standard deviation) of sleep onset time during the previous week was used as an index of irregularity. A Kendall's ranked correlation analysis and a linear regression test were applied to detect correlation between sleep irregularity and the first-night effect measured by polysomnography. RESULTS: There were significant differences in the values of sleep efficiency (p=0.011) and wake after sleep onset (WASO) (p=0.006) between the two nights. Sleep efficiency was lower and WASO was higher on the first night as compared to the second night. Sleep irregularity in the previous week was negatively correlated with sleep efficiency (p<0.001) of the first night, but was not significantly correlated with any other sleep parameters. CONCLUSION: We replicated the existence of the first-night effect commonly observed in sleep studies. Sleep irregularity in the previous week may influence the first-night effect in polysomnographic studies.