北島 剛司

OBJECTIVES: We evaluated the continuity and effectiveness of oral appliances (OAs) for treating obstructive sleep apnea (OSA) in a psychiatric sleep clinic, specifically focusing on mild cases and those with psychiatric comorbidity. METHODS: We retrospectively examined the medical records of 106 OSA patients treated with OA. Survival analysis was performed to assess the discontinuation of OA use. Clinical Global Impression-Improvement (CGI-I) scale were obtained from medical records. The apnea-hypopnea index (AHI), measured by polysomnography (PSG), and Epworth Sleepiness Scale (ESS) were compared between diagnosis and after post-OA treatment if a second PSG for efficacy assessment was conducted. RESULTS: Among all 106 patients, Kaplan-Meier analysis estimated a discontinuation rate of 16.8% at 1 year. This tended to be higher for OSA patients with psychiatric comorbidity (22.7%) than those without (11.6%), though it was not statistically significant (P=0.08). The overall rate of improvement in CGI-I scale was 37.7% and was significantly lower in OSA patients with psychiatric comorbidity (25.0%) than those without (48.3%). Among the 74 patients who underwent a second PSG, AHI and ESS were significantly lower after OA treatment for the entire group and subgroups of OSA severity at diagnosis and psychiatric comorbidity, except for ESS in the moderate OSA severity subgroup. CONCLUSION: OA continuation was relatively good, and sleepiness was relieved by OA use, even in mild OSA patients and those with psychiatric comorbidity. However, the continuation and subjective improvement of symptoms were slightly lower in OSA patients with psychiatric comorbidity.

AIM: Sleep disturbance, a core feature of bipolar disorder, is closely associated with mood symptoms. We examined the association between actigraphy sleep parameters and mood episode relapses in patients with bipolar disorder. METHODS: This prospective cohort study analyzed 193 outpatients with bipolar disorder who participated in the Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. The participants' sleep was objectively evaluated via actigraphy over 7 consecutive days for the baseline assessment and then at the 2-year follow-up appointment for mood episode relapses. The actigraphy sleep parameters were presented using the mean and variability (standard deviation) of each sleep parameter for 7 days. RESULTS: Of the 193 participants, 110 (57%) experienced mood episodes during follow-up. The participants with higher variability in total sleep time had a significantly shorter mean estimated time to mood episode relapses than those with lower variability (12.5 vs. 16.8 months; P < 0.001). The Cox proportional hazards model, when adjusted for potential confounders, demonstrated that variability in total sleep time was significantly associated with an increase in the mood episode relapses (per hour; hazard ratio [HR], 1.407; 95% confidence interval (CI), 1.057-1.873), mainly in the depressive episodes (per hour; HR, 1.477; 95% CI, 1.088-2.006). CONCLUSIONS: Our findings suggest that consistency in sleep time might be useful, as an adjunct therapy, in preventing the recurrence or relapse of mood episodes in bipolar disorder. This article is protected by copyright. All rights reserved.

BACKGROUND: Circadian activity rhythm disruption is a core feature in bipolar disorder. We investigated whether light exposure in daily life is associated with circadian activity rhythms in patients with bipolar disorder. METHODS: In a cross-sectional study, we enrolled 194 outpatients with bipolar disorder who were participants of the Association between Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. The participants' physical activity and daytime illuminance were measured using an actigraph over 7 consecutive days. Nighttime illuminance in the bedroom was measured using a portable photometer. Circadian activity rhythm parameters were calculated using cosinor analysis and a nonparametric circadian rhythm analysis. RESULTS: The median daytime illuminance and nighttime illuminance were 224.5 lx (interquartile range, 154.5-307.5 lx) and 2.3 lx (0.3-9.4 lx), respectively. Multivariable linear regression analysis, adjusted for potential confounding factors, showed that higher daytime illuminance was significantly associated with higher amplitude and most active continuous 10-hour period, advanced acrophase, higher interdaily stability, and lower intradaily variability. Higher nighttime illuminance was significantly associated with lower relative amplitude, delayed onset of the least active continuous 5-hour period, and higher intradaily variability. LIMITATIONS: As this was a cross-sectional study, the results do not necessarily imply that light exposure alters circadian activity rhythms. CONCLUSIONS: Daytime light exposure was associated with a positive effect and nighttime light exposure with a negative effect on circadian activity rhythms in bipolar disorder.

OBJECTIVES: The influence of habitual alcohol consumption on insomnia symptoms in healthy workers remains unclear. In this study, we evaluated the association between habitual alcohol consumption among civil servants and insomnia symptoms such as difficulty falling asleep, difficulty staying asleep, and tiredness after sleep, using longitudinal data. METHODS: We enrolled civil servants in a prospective cohort study who completed questionnaires at baseline. Of those, 2861 participants were revaluated in a 5-year follow-up survey. Insomnia symptoms during the past month were assessed using self-reporting. Alcohol drinking habits were assessed by querying the frequency of drinking alcohol as well as the amount of alcohol usually consumed per one occasion. RESULTS: Drinking alcohol every day was less likely to have difficulty falling asleep (odds ratio, 0.42 95% confidence interval, 0.20-0.89), and drinking alcohol 3 or more days a week was associated with difficulty staying asleep (odds ratio, 1.48; 95% confidence interval, 1.16-1.90). CONCLUSIONS: Drinking alcohol every day may produce subjective improvement in sleep onset. However, drinking alcohol 3 or more days a week may increase arousal during sleep, which contributes to reduced sleep quality. These results suggest the possibility that long-term daily habitual drinking may reinforce a sense of improvement in subjective sleep onset but may possibly induce sleep disturbance.

体内の概日リズムが地球環境の24時間周期に同調できず、社会・日常生活に支障をきたす障害を概日リズム睡眠・覚醒障害(circadian rhythm sleep-wake disorder:CRSWD)という。CRSWDのなかでも、個人の同調能力の問題により、入眠・覚醒困難のため事例化しやすいものが、睡眠・覚醒相後退障害(delayed sleep-wake phase disorder:DSWPD)と非24時間睡眠・覚醒リズム障害(non-24-hour sleep-wake rhythm disorder:N24SWD)である。特に中高生を含めた若齢者に好発するため、この年代が入眠困難を訴えた場合はCRSWDを疑って診察をすることが大切である。病態は依然十分解明されていないが、近年中枢時計の同調障害が主因ではない一群の存在が指摘されている。CRSWDの診断は睡眠日誌などにより行い、治療はメディア使用や体内リズムに関する教育を含めた睡眠衛生指導、メラトニン受容体作動薬などの投与や高照度光療法などの時間生物学的介入を組み合わせて行う。CRSWDは、気分障害、神経発達症の併存や不登校などが背景にあることも多く、これらをあわせて評価し対処することも重要である。(著者抄録)

OBJECTIVE: A previous cross-sectional study reported that nighttime light is associated with increased occurrence of manic symptoms in bipolar disorder; however, the longitudinal association between nighttime light and subsequent mood episode relapses remains unclear. We determined whether bedroom nighttime light was associated with mood episode relapses in patients with bipolar disorder. METHODS: This prospective cohort study included 172 outpatients with bipolar disorder who participated in an Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study. A portable photometer was used to measure illuminance in the bedroom from bedtime to rising time during 7 consecutive nights for baseline assessment. Then, the participants were assessed at a 2-year follow-up for mood episode relapses. RESULTS: Of the 172 participants, 157 (91%) completed the 2-year follow-up, and 39 (22%) experienced manic or hypomanic episodes (with or without mixed features), during that time. In the Cox proportional-hazards model, the hazard ratio (HR) for manic/hypomanic episode relapses was significantly higher when the average nighttime illuminance was ≥3 lux (n = 71) than when it was <3 lux (n = 101; HR, 2.54; 95% confidence interval (CI), 1.33-4.84). In the multivariable model adjusted for a propensity score in relation to nighttime light, the relationship remained significant (HR, 2.17; 95% CI, 1.04-4.52). The association between nighttime light and depressive episode relapses was not significantly different. CONCLUSIONS: Keeping the bedroom dark at night may prevent hypomanic and manic episodes.

Delayed sleep phase disorder (DSPD) and mood disorders have a close relationship. However, the shared mechanisms by DSPD and mood disorders have not been well-elucidated. We previously found that micro-fluctuations in human behaviors are organized by robust statistical laws (behavioral organization), where the cumulative distributions of resting and active period durations take a power-law distribution form and a stretched exponential functional form, respectively. Further, we found that the scaling exponents of resting period distributions significantly decreased in major depressive disorder (MDD). In this study, we hypothesized that DSPD had similar characteristics of the altered behavioral organization to that of MDD. Locomotor activity data were acquired for more than 1 week from 17 patients with DSPD and 17 age- and gender-matched healthy participants using actigraphy. We analyzed the cumulative distributions of resting and active period durations in locomotor activity data and subsequently derived fitting parameters of those distributions. Similar to patients with MDD, we found that resting period distributions took a power-law form over the range of 2-100 min, with significantly lower values of scaling exponents γ in patients with DSPD compared with healthy participants. The shared alteration in γ suggests the existence of similar pathophysiology between DSPD and MDD.

BACKGROUND: Sleep disturbance is a core feature of bipolar disorder; hence, sleep must be accurately assessed in patients with bipolar disorder. Subjective sleep assessment tools such as sleep diary and questionnaires are often used clinically for assessing sleep in these patients. However, the insight into whether these tools are as accurate as objective tools, such as actigraphy, remains controversial. METHODS: This cross-sectional study included 164 outpatients with a diagnosis of bipolar disorder, including patients who had euthymic and residual symptomatic periods. Objective sleep assessment was conducted prospectively using actigraphy for 7 consecutive days, whereas subjective sleep assessment was conducted prospectively using a sleep diary. RESULTS: The correlations were high and moderate between sleep diary and actigraphy when assessing the total sleep time and sleep onset latency, respectively (r = 0.81 and 0.47). These correlations remained significant after correction for multiple testing (both p < 0.001) and in both euthymic and residual symptomatic states (total sleep time: r = 0.86 and 0.77; sleep onset latency: r = 0.51 and 0.40, respectively). The median (interquartile ranges) of the percentage difference (sleep diary parameters minus actigraphy parameters divided by actigraphy parameter) in the total sleep time was relatively small (6.2% [-0.2% to 13.6%]). CONCLUSIONS: Total sleep time assessment using a sleep diary could be clinically useful in the absence of actigraphy or polysomnography.

A significant proportion of patients with bipolar disorder experience mood episode relapses. We examined whether circadian activity rhythms were associated with mood episode relapses in patients with bipolar disorder. This prospective cohort study included outpatients with bipolar disorder who participated in a study titled "Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study." The participants' physical activity was objectively assessed using a wrist-worn accelerometer over 7 consecutive days for the baseline assessment and then at the 12-month follow-up for mood episode relapses. The levels and timing of the circadian activity rhythms were estimated using a cosinor analysis and a nonparametric circadian rhythm analysis. Of the 189 participants, 88 (46%) experienced mood episodes during follow-up. The Cox proportional hazards model adjusting for potential confounders showed that a robust circadian activity rhythm, including midline-estimating statistic of rhythm (MESOR) and amplitude by cosinor analysis and 10 consecutive hours with the highest amplitude values (M10) by the nonparametric circadian rhythm analysis, was significantly associated with a decrease in mood episode relapses (per counts/min, hazard ratio [95% confidence interval]: MESOR, 0.993 [0.988-0.997]; amplitude, 0.994 [0.988-0.999]; and M10, 0.996 [0.993-0.999]). A later timing of the circadian activity rhythm (M10 onset time) was significantly associated with an increase in the depressive episode relapses (per hour; 1.109 [1.001-1.215]). We observed significant associations between circadian activity rhythms and mood episode relapses in bipolar disorder.

Despite the increasing knowledge on the association between neighborhood and health, few studies have investigated sleep disorders in Japan, particularly the impact of neighborhood noise on sleep. Thus, this study aimed to investigate the associations between insomnia symptoms and annoyance because of traffic and neighborhood noise in Japan, which has different neighborhood conditions compared with those of the western societies. Neighborhood built and socioeconomic environments roles were also examined. We used nationwide cross-sectional data collected through a 2015 online survey of Japanese adults aged 20–64 years (n = 4,243). Adjusted prevalence ratios for insomnia according to the exposures were estimated using the multilevel Poisson regression models. The results showed that having insomnia was significantly associated with experiencing neighborhood and traffic-noise annoyance. Neighborhood noise had a stronger and independent association with insomnia. However, the neighborhood environmental variables, including population density, deprivation index, and access to commercial areas, were not associated with insomnia. In conclusion, noise annoyance, particularly that sourced from neighbors, is an important factor in relation to sleep health. Health and urban-planning policymakers should consider neighborhood noise, in addition to traffic noise, as health-related issues in residential neighborhoods.

OBJECTIVE: Light therapy has been suggested to have a curative effect on bipolar depression; however, preventive effects of light exposure on depressive episodes remain unclear. This study evaluated whether daytime light exposure in real-life situations was associated with a preventive effect on relapse into depressive episodes in patients with bipolar disorder. METHODS: This prospective, naturalistic, observational study was conducted in Japan between August 2017 and June 2020. Outpatients with bipolar disorder were objectively evaluated for daytime light exposure over 7 consecutive days using an actigraph that could measure ambient light at baseline assessment and then assessed at 12-month follow-up for relapse into mood episodes. RESULTS: Of 202 participants, 198 (98%) completed follow-up at 12 months and 78 (38%) experienced relapse into depressive episodes during follow-up. In a Cox proportional hazards model adjusting for potential confounders, a longer time above 1000 lux at daytime was significantly associated with decrease in relapse into depressive episodes (per log min; hazard ratio, 0.66; 95% confidence interval, 0.50-0.91). In addition, a higher average illuminance and longer time above 1000 lux in the morning exhibited a significant decrease in relapse into depressive episodes (per log lux and per log min; hazard ratio, 0.65 and 0.61; 95% confidence interval, 0.49-0.86 and 0.47-0.78, respectively). The association between daytime light exposure and relapse into manic/hypomanic/mixed episodes was not significantly different. CONCLUSION: A significant association was observed between increased daytime light exposure, mainly in the morning, and decreased relapse into depressive episodes.

OBJECTIVE: Sleep disturbance, a core feature of bipolar disorder, is associated with residual mood symptoms, mood episode recurrence and suicide ideation. We investigated the effect of evening light exposure on sleep in patients with bipolar disorder. METHODS: In this longitudinal analysis, we measured the sleep parameters of 207 outpatients with bipolar disorder using actigraphy at their homes for seven consecutive nights. We measured the white-light illuminance and the irradiance of each wavelength during the 4 hours before each participant's bedtime. We used mixed-effect linear regression analysis for repeated measures to evaluate the effect of evening light exposure on subsequent sleep parameters. RESULTS: The median white-light illuminance was 25.8 lux (interquartile range, 12.9-50.1 lux). In a multivariable model adjusted for potential confounders, we found higher white-light illuminance to be significantly associated with lower sleep efficiency (per log lux: 95% confidence interval = [-1.328, -0.133]; p = 0.017), prolonged sleep-onset latency (95% confidence interval = [0.006, 0.172]; p = 0.035) and longer wake after sleep onset (95% confidence interval = [1.104, 4.459]; p = 0.001). This effect size was larger in the younger age group (aged < 44 years) stratified by median age. Higher irradiance of the blue wavelength range was significantly associated with longer wake after sleep onset, a result similar to those for the green and red wavelength ranges. CONCLUSION: We observed significant associations between evening light exposure and subsequent sleep in patients with bipolar disorder. The effects of various light wavelengths on sleep in bipolar disorder require further investigation.

Obesity and overweight are highly prevalent in individuals with bipolar disorder and are associated with a risk of developing not only physical but also mental problems. The current study aimed to determine the association between bedroom light exposure at night and obesity in individuals with bipolar disorder. This cross-sectional study enrolled 200 outpatients with bipolar disorder. The light intensity in the bedroom between bedtime and rising time was measured for seven consecutive nights using a portable photometer. Body mass index (BMI) was determined using self-reported height and weight, and obesity was defined as a BMI ≥ 25 kg/m2. The overall prevalence of obesity was 44%. In the multivariable logistic regression analysis adjusted for age, gender, use of psychiatric medications, sleep parameters, and physical activity, the odds ratio (OR) for obesity was significantly higher in the group exposed to an average light intensity ≥ 3 lux (n = 112) than in the group exposed to an average light intensity < 3 lux (n = 88) (OR, 2.13; 95% confidence interval, 1.19-4.21; P = 0.01). Furthermore, individuals exposed to an average light intensity ≥ 3 lux were significantly higher body weight (adjusted mean, 68.7 vs. 64.4 kg; P = 0.03) and BMI (adjusted mean, 25.6 vs. 24.2 kg/m2; P = 0.04) than those exposed to an average light intensity < 3 lux. A significant association was observed between bedroom light exposure at night and obesity in patients with bipolar disorder. Further longitudinal investigations are necessary to clarify this association.

BACKGROUND: Patients with bipolar disorder (BD) frequently self-harm, and this is strongly associated with subsequent suicide. This study investigated the association between chronotype and intentional self-harm in patients with BD. METHODS: Two-hundred and five outpatients with BD participated in this cross-sectional study. Each participant's chronotype was evaluated using the Morningness-Eveningness Questionnaire, dividing the scores into three types: evening, 16-41 points; intermediate, 42-58 points; and morning, 59-86 points. Intentional self-harm over the past year were self-reported by questionnaire. Propensity score for evening chronotype was estimated from age, sex, socioeconomic factors, mood symptoms, total sleep time, age at the onset of BD, psychiatric inpatient history, family history of suicide, psychiatric comorbidity, and use of lithium. RESULTS: Thirty-six (18%) of the 205 participants reported self-harm. A substantially higher proportion of the evening chronotype group self-harmed compared to the other groups (evening, 37%; intermediate, 13%; morning 10%). In multivariable analysis adjusted for propensity score, the odds ratio (OR) for self-harming significantly increased from morning to intermediate to evening chronotype (ORs: morning, 1.00; intermediate, 1.56; evening, 3.61; P for trend = 0.038). LIMITATIONS: This study was a cross-sectional and small sample size. CONCLUSIONS: Although a third factors, such as personality disorder or disrupted circadian rhythm, may have influenced, these findings suggest association between chronotype and intentional self-harm in BD patients.

・注意欠如・多動症(ADHD)と自閉スペクトラム症(ASD)は成人においても睡眠・覚醒リズムの乱れを伴うことが多いことが指摘されており、社会生活の困難をもたらす要因の1つであるため、病態の解明が求められている。その機序としては、両障害の認知ないし行動の特性の影響、気分障害やむずむず脚症候群などの併存症の介在なども考えられるほか、メラトニン分泌リズムの変調や時計遺伝子変異の関連など、概日リズム機構の関与も諸研究より指摘されている。神経発達症で想定されるドパミン系の病態や、synaptic homeositasis仮説などより、睡眠恒常性との関連も検討する価値があるのではないかと思われる(著者抄録)

OBJECTIVES: Recent studies have suggested that evening blue light exposure is associated with sleep and circadian rhythm abnormalities. This study examined the effect of blue-blocking (BB) glasses on sleep and circadian rhythm in patients with bipolar disorder (BD). METHODS: We used a randomized, placebo-controlled, double-blinded design. Outpatients with BD and also with insomnia were randomly assigned to wear either orange glasses (BB) or clear ones (placebo) and were instructed to use these from 20:00 hours until bedtime for 2 weeks. The primary outcome metric was the difference in change from baseline to after intervention in sleep quality, as measured by the visual analog scale (VAS). RESULTS: Forty-three patients were included in this study (BB group, 21; placebo group, 22). The change in sleep quality as per the VAS metric was not significantly different between the two groups (95% confidence interval [CI], -3.34 to 24.72; P = .13). However, the Morningness-Eveningness Questionnaire score had shifted to an advanced rhythm in the BB group and to a delayed rhythm in the placebo group, and the difference in these changes was statistically significant (95% CI, 1.69-7.45; P = .003). The change in the actigraphy sleep parameters and mood symptoms was not significantly different between the two groups. CONCLUSION: Although concurrent medications may have influenced, our results suggest that BB glasses may be useful as an adjunctive treatment for circadian rhythm issues in patients with BD.

＜Key Point＞・気分障害と睡眠障害は密接かつ相互に関連しあい、症状の遷延や治療複雑化の要因となりうる・多岐に渡る睡眠障害の適切な診断と治療は気分障害の寛解を目指すにあたり必要不可欠である(著者抄録)

BACKGROUND: The minimum narcolepsy criteria "mean sleep latency (MSL) ≤8 min and ≥2 sleep onset rapid eye movement (REM) periods (SOREMPs) on polysomnography (PSG) and the multiple sleep latency test (MSLT)," according to The International Classification of Sleep Disorders, Third Edition (ICSD-3), are not specific to narcolepsy. Recently, the characteristic sleep stage sequences preceding SOREMPs in narcolepsy have received attention, but their diagnostic utility remains unclear. METHODS: We retrospectively reviewed PSG/MSLT records and chart data for 102 Japanese patients with hypersomnia and at least one SOREMP. We examined the sporadic rates of two sleep stage sequences preceding the SOREMPs-wakefulness or stage 1 to REM (W/S1→R) and stage 2 to REM (S2→R)-comparing these between patient groups with narcolepsy type 1 (N = 28), narcolepsy type 2 (N = 19), and other hypersomnia (N = 55). We also examined the utility of three simple indices using the occurrence of W/S1→R SOREMPs for distinguishing between narcolepsy and other hypersomnia in patients who satisfied the minimum narcolepsy criteria. RESULTS: W/S1→R SOREMPs were significantly more frequent in narcolepsy than in other hypersomnia, and this tendency was also observed even in the patients who satisfied the minimum narcolepsy criteria. The three indices had moderate sensitivities and specificities for distinguishing between narcolepsy and other hypersomnia in patients satisfying the minimum narcolepsy criteria. CONCLUSIONS: The W/S1→R pattern was observed significantly more frequently in narcolepsy than in other hypersomnia, suggesting it may help with differentiating narcolepsy from other hypersomnia in patients demonstrating the narcolepsy criteria, although its ability to do so may be modest.

Previous studies have found that keeping the room dark at night was associated with a decrease in manic symptoms for patients with bipolar disorder (BD). However, the association between light at night of real-life conditions and manic symptoms is unclear. We investigated the association between bedroom light exposure at night and manic symptoms in BD patients. One-hundred and eighty-four outpatients with BD participated in this cross-sectional study. The average light intensity at night during sleep was evaluated using a portable photometer for seven consecutive nights. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS), and scores ≥5 were treated as a "hypomanic state." The median (interquartile range) YMRS score was 2.0 (0-5.0), and 52 (28.2%) participants were in a hypomanic state. The prevalence of a hypomanic state was significantly higher in the participants with an average light intensity at night exposure of ≥3 lux than in those with <3 lux (36.7% versus 21.9%; P = .02). In multivariable logistic regression analysis adjusted for BD type, depressive symptoms, sleep duration, and daytime physical activity, the odds ratio (OR) for a hypomanic state was significantly higher for the participants with an average light intensity at night exposure of ≥3 lux than for those with <3 lux (OR: 2.15, 95% confidence interval: 1.09-4.22, P = .02). This association remained significant at the cutoff value of YMRS score ≥6 (OR: 2.51, 95% confidence interval: 1.15-5.46; P = .02). The findings of this study indicate bedroom light exposure at night is significantly associated with manic symptoms in BD patients. Although the results of this cross-sectional investigation do not necessarily imply causality, they may serve to inform beneficial nonpharmacological intervention and personalized treatment of BD patients.

BACKGROUND: Sleep disturbance in bipolar disorder (BD) is common and is associated with a risk for mood episode recurrence. Thus, it is important to identify factors that are related to sleep disturbance in BD. This cross-sectional study investigated the association between exposure to light at night (LAN) and sleep parameters in patients with BD. METHODS: The sleep parameters of 175 outpatients with BD were recorded using actigraphy at their homes for seven consecutive nights and were evaluated using the Insomnia Severity Index (ISI). The average LAN intensity in the bedroom during bedtime and rising time was measured using a portable photometer, and the participants were divided into two groups: "Light" (≥5 lx) and "Dark" (<5 lx). The association between LAN and sleep parameters was tested with multivariable analysis by adjusting for potential confounder such as age, gender, current smoker, mood state, day length, daytime light exposure, and sedative medications. RESULTS: After adjusting for potential confounder, the actigraphy sleep parameters showed significantly lower sleep efficiency (mean, 80.1%vs. 83.4%; p = 0.01), longer log-transformed sleep onset latency (2.9 vs. 2.6 min; p = 0.01), and greater wake after sleep onset (51.4 vs. 41.6 min; p = 0.02) in the Light group than in the Dark group. Whereas, there were no significant differences in the ISI scores between the groups. LIMITATIONS: This was a cross-sectional study; therefore, the results do not necessarily imply that LAN causes sleep disturbance. CONCLUSIONS: Reducing LAN exposure may contribute to improved sleep quality in patients with BD.

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 '9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 '10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 '9), TRANK1 (P best =2.1 × 10 '9) and ODZ4 (P best =3.3 × 10 '9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ∼10 '29, R 2 ∼2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ∼10 '13, R 2 ∼0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates∼0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

The objective of the study was to investigate the efficacy of ramelteon for insomnia, particularly with circadian disturbance, focusing on the relevance of dose and timing of administration. We reviewed the chart data of 145 continuous patients who received ramelteon for insomnia for the first time at the sleep clinic of the Department of Psychiatry, Fujita Health University Hospital (Aichi, Japan) between October 2010 and May 2014. Treatment efficacy was assessed using the Clinical Global Impression of Improvement (CGI-I) scale and this relationship with the dose and timing of administration was further analyzed. Symptoms in 56.6% of patients were improved (CGI-I ≦ 3). In a subgroup of 114 patients, especially aiming for phase advance, the ratio of improvement was 64.0%. The ratio of patients reporting symptom improvement tended to be great in the low-dose (1 or 2 mg) group and the low-dose + early administration (&gt 5 h before habitual bedtime) group, as compared with the remaining group however, this difference was not statistically significant. Significantly fewer cases in the low-dose group reported carry-over effects. In our specialized sleep clinic, there were many refractory cases of insomnia however, ramelteon was effective in about half of such patients. Particularly, ramelteon tended to be more effective for patients with insomnia and circadian disturbances, although differences among groups were not statistically significant. The effectiveness of the low-dose administration or the combination of low-dose and early-administration was equal or slightly better and acceptability tended to be better than other modes of administration.

We describe a case of parasomnia overlap disorder (POD) caused by paroxetine. Some reports have associated antidepressants such as selective serotonin reuptake inhibitors (SSRI) with rapid eye movement sleep behavior disorder. However, to the best of our knowledge, there have been no reports of POD caused by paroxetine. We diagnosed POD in a patient taking paroxetine using video-polysomnography (v-PSG) and then confirmed the improvement of POD symptoms by v-PSG after discontinuing the drug.