Ranking important predictors of the need for a high-acuity psychiatry unit among 2,064 inpatients admitted to psychiatric emergency hospitals: a random forest model.

Aims: In order to uphold and enhance the emergency psychiatric care system, a thorough comprehension of the characteristics of patients who require a high-acuity psychiatry unit is indispensable. We aimed to clarify the most important predictors of the need for a high-acuity psychiatry unit using a random forest model. Methods: This cross-sectional study encompassed patients admitted to psychiatric emergency hospitals at 161 medical institutions across Japan between December 8, 2022, and January 31, 2023. Questionnaires were completed by psychiatrists, with a maximum of 30 patients assessed per medical institution. The questionnaires included psychiatrists' assessment of the patient's condition (exposure variables) and the need for a high-acuity psychiatry unit (outcome variables). The exposure variables consisted of 32 binary variables, including age, diagnoses, and clinical condition (i.e., factors on the clinical profile, emergency treatment requirements, and purpose of hospitalization). The outcome variable was the need for a high-acuity psychiatry unit, scored from 0 to 10. To identify the most important predictors of the need for a high-acuity psychiatry unit, we used a random forest model. As a sensitivity analysis, multivariate linear regression analysis was performed. Results: Data on 2,164 patients from 81 medical institutions were obtained (response rate, 50.3%). After excluding participants with missing values, this analysis included 2,064 patients. Of the 32 items, the top-5 predictors of the need for a high-acuity psychiatry unit were the essentiality of inpatient treatment (otherwise, symptoms will worsen or linger), need for 24-hour professional care, symptom severity, safety ensured by specialized equipment, and medication management. These items were each significantly and positively associated with the need for a high-acuity psychiatry unit in linear regression analyses (p < 0.001 for all). Conversely, items on age and diagnosis were lower in the ranking and were not statistically significant in linear regression models. Conclusion: Items related to the patient's clinical profile might hold greater importance in predicting the need for a high-acuity psychiatry unit than do items associated with age and diagnosis.

Circadian variability of objective sleep measures predicts the relapse of a mood episode in bipolar disorder: findings from the APPLE cohort.

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 seven 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.

Habitual light exposure and circadian activity rhythms in bipolar disorder: A cross-sectional analysis of the APPLE cohort.

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.

Effect of nighttime bedroom light exposure on mood episode relapses in bipolar disorder.

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.

Driving performance of euthymic outpatients with bipolar disorder undergoing real-world pharmacotherapy.

OBJECTIVE: Medications for the treatment of bipolar disorder (BD) could affect patients' cognitive function. Patients with BD present with neurocognitive impairment even in a remission state. Little research is available on the daily functioning, especially driving performance, of stable outpatients with BD under pharmacological treatment. METHODS: In total, 58 euthymic outpatients with BD undergoing real-world pharmacotherapy and 80 sex- and age-matched healthy controls (HCs) were enrolled. Three driving tasks using a driving simulator-road-tracking, car-following, and harsh-braking-and three cognitive tasks-Continuous Performance Test, Wisconsin Card Sorting Test, and Trail-Making Test-were evaluated. Symptom assessment scales-Young Mania Rating Scale, Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory-II, Social Adaptation Self-evaluation Scale, and Stanford Sleepiness Scale-were also completed. RESULTS: Car-following and road-tracking performance were significantly impaired in patients with BD compared with HCs after adjusting for demographic variables, but these performances generally overlapped. Broad neurocognitive functions were significantly lower in the patients with BD compared to HCs, but car-following performance was significantly negatively correlated with sustained attention only. Although most patients received multiple medications rather than monotherapy, no relationship between prescriptions and driving performance was found. CONCLUSION: Euthymic patients with BD under steady-state pharmacotherapy had impaired driving performance compared with HCs, but the overlapping distributions of driving performance suggested that driving performance is not always deteriorated in patients with BD. Therefore, attentional function may be a useful clinical feature for judging driving aptitude in patients with BD.

Discontinuation and remission rates and social functioning in patients with schizophrenia receiving second-generation antipsychotics: 52-week evaluation of JUMPs, a randomized, open-label study.

AIM: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety. RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. CONCLUSION: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.

Real-world effectiveness of antipsychotic treatments in 1011 acutely hospitalized patients with schizophrenia: A one-year follow-up study.

PURPOSE: To compare the real-world effectiveness of antipsychotic treatments focusing on long-acting injectable antipsychotic medications (LAIs) and antipsychotic polytherapies except polytherapy involving clozapine (APEC) for patients with schizophrenia. METHODS: This prospective study was conducted over a 19-month period in 12 psychiatric emergency hospitals in Japan. Patients who were newly admitted to psychiatric emergency wards between September 2019 and March 2020 because of acute onset or exacerbation of Schizophrenia and Other Psychotic Disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. All patients were followed for one-year after discharge or until March 31, 2021. The primary outcome was the risk of treatment failure defined as psychiatric rehospitalization, discontinuation of medication, death, or continuation of hospitalization for one year. Cox proportional hazards multivariate regression was used for analyses. RESULTS: A total of 1011 patients were enrolled (women, 53.7%; mean [SD] age, 47.5 [14.8] years). During follow-up, 588 patients (58.2%) experienced treatment failure including rehospitalization (513 patients), discontinuation of medication (17 patients), death (11 patients), and continuation of hospitalization for one-year (47 patients). Switching to LAIs (hazard ratio [HR] 0.810, 95%CI 0.659-0.996) and APEC (HR 0.829, 95%CI 0.695-0.990) were significantly associated with a low rate of treatment failure. CONCLUSIONS: Switching to LAIs and APEC in early non-responders seems to be beneficial for the prevention of treatment failure in acutely admitted patients with schizophrenia. The risk of treatment failure was about 19% and 17% lower in patients treated with LAIs and APEC, respectively, than in patients treated without them.

Comparison of objective and subjective sleep parameters in patients with bipolar disorder in both euthymic and residual symptomatic periods.

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.

Association between circadian activity rhythms and mood episode relapse in bipolar disorder: a 12-month prospective cohort study.

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.

Usefulness of a psychomotor function test as a cognitive function scale for patients with schizophrenia: A pilot study.

As cognitive dysfunction due to schizophrenia is strongly associated with patients' social rehabilitation, cognitive functions have been examined as a therapeutic target. Although the Brief Assessment of Cognition in Schizophrenia (BACS) has been used to evaluate cognitive function, it is difficult to administer in routine clinical practice due to its time-consuming nature. Therefore, a novel tool is needed to facilitate the assessment of cognitive function. In the present study, we examined whether cognitive function can be assessed effectively by testing psychomotor function in patients with schizophrenia. Test batteries consisting of choice reaction time (CRT) and compensatory tracking task (CTT) and the BACS were examined in 20 schizophrenic patients to evaluate the correlation between the scales by Pearson correlation coefficient. Of the test batteries, the CRT was significantly correlated with attention functions, a subtest of the BACS (r = -0.506, p = 0.023), and the CTT was strongly correlated with attention functions (r = -0.716, p < 0.001) and working memory (r = -0.633, p = 0.003). A multiple regression analysis was performed to clarify the association between psychomotor function tests and the total BACS score, and peripheral awareness task, a component of CTT, was independently associated with the total BACS score (ß = -0.59, p = 0.004) with an R2 of 0.37. Thus, of the psychomotor function tests, the CRT and the CTT are highly useful in assessing cognitive functions in schizophrenic patients. However, no having large sample size in this study is a limitation.

Preventive effect of morning light exposure on relapse into depressive episode in bipolar disorder.

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.

Bedroom light exposure at night and obesity in individuals with bipolar disorder: A cross-sectional analysis of the APPLE cohort.

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.

Effect of evening light exposure on sleep in bipolar disorder: A longitudinal analysis for repeated measures in the APPLE cohort.

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.

Higher prevalence of intentional self-harm in bipolar disorder with evening chronotype: A finding from the APPLE cohort study.

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.

A randomized-controlled trial of blonanserin and olanzapine as adjunct to antipsychotics in the treatment of patients with schizophrenia and dopamine supersensitivity psychosis: The ROADS study.

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

Recurrence of Mania or Depression Among Adult Bipolar Patients Who Continued Using Lithium: A Single-group Summary Meta-analysis of Randomized Trials.

BACKGROUND: The exact recurrence rate of bipolar disorder in patients receiving lithium maintenance phase treatment and the modifiers associated with recurrence are still unknown. METHODS: We searched Embase, PubMed, and CENTRAL from inception until April 28, 2020. Outcomes included recurrence rate of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes; all-cause discontinuation rate; and discontinuation rate due to adverse events. A random-effects model, single-group summary meta-analysis was conducted. A meta-regression analysis to examine whether the modifiers (total number of patients, %female, mean age, duration of study, duration of preliminary phase, publication year, bipolar disorder type, mood status at recruitment, presence of a placebo arm, sponsorship, enrichment design, number of treatment arms, and risk of bias for blinding or randomization) were associated with the event rate of the outcomes was also performed. RESULTS: We identified 21 randomized trials (n = 1,415; mean study duration, 78.40 ± 32.10 weeks; %female, 54.85%; mean age, 43.47 ± 4.88 years). The event rates (95% confidence interval [CI]) were as follows: recurrence of any mood episode, 39.8% (32.8%, 47.1%); depressive episodes, 25.6% (18.8%, 34.0%); manic/hypomanic/mixed episodes, 18.5% (13.7%, 24.7%); all-cause discontinuation rate, 67.0% (57.2%, 75.5%); and discontinuation rate due to adverse events, 8.7% (5.1%, 14.7%). After adjusting for multiple testing, our meta-regression analysis showed association only between the all-cause discontinuation rate and presence of a placebo arm. CONCLUSIONS: The recurrence rate of depressive episodes seemed to be higher than the recurrence rate of manic/hypomanic/mixed episodes. The all-cause discontinuation rate was high. However, the studies included in our meta-analysis were of short duration.

A double-blind, randomized, placebo-controlled trial of adjunctive blue-blocking glasses for the treatment of sleep and circadian rhythm in patients with bipolar disorder.

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.

Association between light exposure at night and manic symptoms in bipolar disorder: cross-sectional analysis of the APPLE cohort.

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 of the neuropathological site in neurocognitive decline in elderly schizophrenic patients.

We herein report the neuropathological findings of a schizophrenic patient who showed cognitive decline and deterioration of psychiatric symptoms in his elderly years. In the neuropathological investigation in this case, Alzheimer-type pathology and argyrophilic grain pathology were observed. Schizophrenic patients can sometimes show cognitive decline in later life as an intrinsic symptom. However, they may also be complicated with dementia in later life, although these complications in a clinical setting have not been well examined. Few reports have investigated whether or not schizophrenic patients are likely to be complicated with dementia, and the findings remain controversial. We confirmed relatively mild ageing changes neuropathologically in the present case. How much these pathological changes influenced his psychiatric symptoms is unclear, but these changes were thought to have some degree of relevance. We also discuss the relationship between schizophrenia and dementia. We should remain alert to the fact that even schizophrenic patients can contract neurodegenerative diseases as a dual diagnosis in their clinical course and that they can show complicated symptoms. Further investigations of the clinical-pathological relationship between schizophrenia and dementia are thus needed.