The effect of lemborexant on insomnia in patients with psychiatric disorders: Detailed evaluation using the Athens Insomnia Scale.

Aim: Chronic insomnia disorder is common and associated with reduced quality of life. Benzodiazepine hypnotics are commonly prescribed for insomnia, but have potential side effects such as concentration impairment, somnolence, and dependence. Lemborexant (LEM) is an orexin receptor antagonist considered to have fewer side effects than benzodiazepine hypnotics. This study evaluated the effect of LEM on sleep in detail and examined whether benzodiazepine hypnotics can be gradually tapered by adding LEM. Methods: We retrospectively examined the effectiveness of LEM in 28 outpatients with insomnia. Insomnia symptoms were assessed using the Athens Insomnia Scale (AIS) before and after LEM administration. We also attempted to taper benzodiazepine hypnotics and assessed benzodiazepine dose using diazepam equivalents for some patients taking benzodiazepine hypnotics. Wilcoxon's signed-rank test was used for statistical analysis. Results: The mean AIS score was significantly improved after LEM treatment (8.7 ± 5.2 vs. 3.8 ± 3.3; P < 0.01). Among the AIS subitems, significant improvement was observed for six items: sleep induction, awakenings during the night, sleep quality, well-being, functioning capacity, and sleepiness during the day. The mean benzodiazepine dose was significantly lower after LEM treatment (4.6 ± 5.0 mg vs. 2.1 ± 3.3 mg; P < 0.01). Conclusions: This study indicated the potential of LEM for improving insomnia and reducing benzodiazepine dose.

Changes in health-related quality of life in patients admitted to emergency departments for attempted suicide: Findings from a large longitudinal study.

BACKGROUND: Studies of quality of life among suicide attempters are limited while it is considered important for preventing reattempt of suicide. We investigated health related quality of life (HRQoL) in suicide attempters immediately after the suicide attempt and in the long term. METHODS: This was longitudinal data from a randomized controlled multicenter trial. The Japanese version of the Short Form Health Survey-36 as HRQOL measured at 0, 6, and 12 months after randomization. RESULTS: 799 patients (356 men and 443 women) were analyzed. At baseline, the mean physical component summary (PCS) and the mental component summary (MCS) scores were 34.56 and 35.15, respectively, and they were significantly low compared with those of the general population. PCS scores significantly improved from baseline to 6 months (p = 0.003), from baseline to 12 months (p < 0.0001), and from baseline to 12 months (p = 0.002). MCS scores significantly improved from baseline to 6 months (p < 0.0001) and from baseline to 12 months (p < 0.0001). However, neither PCS nor MCS scores reached those of the general population norm at 12 months post-suicide attempt. LIMITATIONS: Patients younger than 20 years and patients who self-harmed but were not admitted to an emergency department were excluded. CONCLUSION: This study presents a trajectory of HRQoL scores in suicide attempters from immediately after the suicide attempt to 1 year later. Further studies on HRQoL in suicide attempters are needed to elucidate the effective care for the attempters.

Multi-institutional survey of suicide death among inpatients with schizophrenia in comparison with depression.

Suicide is a major cause of death among inpatients with schizophrenia. However, there are only a limited number of surveys of suicide among such patients, especially in Asia. Therefore, we conducted a multi-institutional survey on suicide death among inpatients with schizophrenia in Japan. We investigated the characteristics of patients with schizophrenia who died by suicide during hospitalization in psychiatric wards, and simultaneously, those of patients with depression. Forty-five suicides of patients with schizophrenia occurred in 27 hospitals, and 46 suicides of patients with depression occurred in 33 hospitals. Hanging was the most common suicide method in both diagnostic groups. More than half of the patients with schizophrenia had histories of suicide attempts, although there was no significant difference in previous suicide attempts or self-harm between both diagnostic groups. Medical staff should confirm whether inpatients with schizophrenia have such histories. In this study, there was no significant difference in characteristics between inpatients with schizophrenia or depression. In order to prevent suicides of patients with schizophrenia during hospitalization, nonspecific suicide attempt prevention needs to be undertaken, such as ensuring comprehension of the general risk factors of suicide among medical staff.

Ecotypic divergences of the alpine herb Potentilla matsumurae adapted to fellfield-snowbed habitats across a series of mountain sky islands.

PREMISE: Divergent selection due to environmental heterogeneity can lead to local adaptation. However, the ecological and evolutionary processes of local adaptation that occurs across multiple regions are often unknown. Our previous studies reported on the ecotypic divergence within a local area of variation of Potentilla matsumurae, an alpine herb adapted to the fellfield-snowbed environment. Here we investigated large-scale geographic patterns of ecotypic differentiation in this species to infer local adaptation and selective forces across multiple regions. METHODS: We compiled information on the overall distributions of fellfield and snowbed habitats on the mountains in Japan across the distribution of the species. Next, we conducted common garden experiments to test the adaptive divergence of the fellfield-snowbed plants derived from multiple regions. Finally, we evaluated phylogeographic structures based on cpDNA and allozyme variations and inferred the evolutionary history of ecotype differentiation. RESULTS: The mosaic distribution of the fellfield-snowbed ecotypes across isolated mountaintops constitutes indirect evidence for habitat-specific natural selection. The significant difference in survivorship between the ecotypes observed in a controlled snow environment provides more substantial evidence of local selection. Phylogeographic structures support the hypothesis that ecotypic divergence events from fellfield to snowbed populations occurred independently in at least two distinct regions. CONCLUSIONS: Ecotypic divergence of P. matsumurae has occurred across a series of mountain sky islands. Local selection in snowy environments is a driving force that maintains the divergent ecotypes across multiple mountain regions and can contribute to the diversification of plants in heavy-snow regions.

Psychiatric Consultations at an Emergency Department in a Metropolitan University Hospital in Northern Japan.

Many patients with mental disorders visit emergency departments (EDs). However, the majority of these patients do not receive psychiatric assessment. In the present study, we investigated the detailed proportion of patients with mental disorders visiting an urban ED in the largest northern city in Japan. A retrospective chart review study was performed at a University Hospital from January 2012 to December 2015. The reasons for psychiatric consultations made by ED staff, and the primary psychiatric diagnoses were investigated. Among all living patients, 20% of them received consultations. The most common reason for consultation was suicide attempt followed by agitation or insomnia. Of all diagnoses, organic mental disorder was the most frequent and the mean age was significantly higher than the other diagnostic groups. Our study indicated that the frequency of psychiatric consultation was high. This indicates the high demand for mental health services at the ED. A thorough psychiatric assessment can provide adequate psychiatric services to acute patients; thereby possibly preventing suicide attempters from later actually dying by suicide.

Regulation of synthesis of osteoprotegerin and soluble receptor activator of nuclear factor-kappaB ligand in normal human osteoblasts via the p38 mitogen-activated protein kinase pathway by the application of cyclic tensile strain.

Mechanical stress is thought to play an important role in bone remodeling. However, the correlation between mechanical stress and bone remodeling is poorly understood. In this context, using a model of cyclic tensile strain (CTS) toward human osteoblasts, synthesis of osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and the activation of mitogen-activated protein kinases (MAPKs) were examined. The application of 7%, 0.25-Hz CTS once a day for 4 h for 3 successive days simultaneously caused an increase of OPG synthesis and a decrease of sRANKL release and RANKL mRNA expression in osteoblasts. As for MAPKs activation in osteoblasts with the application of CTS, p38 MAPK was activated 10-20 min after the application of CTS, but extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK) were not activated by such application. Furthermore, when CTS was applied once a day for 4 h for 1, 2, or 3 successive days to osteoblasts, p38 MAPK activation was maintained during the 3-day period but ERK1/2 activation was downregulated from day to day, simultaneously. Then, when CTS was applied once a day for 4 h for 3 successive days to osteoblasts pretreated with the p38 MAPK inhibitor SB203580 for 1 h, OPG synthesis was dose-dependently suppressed and inhibition of sRANKL release and RANKL mRNA expression was abrogated. These results indicate that biological responses of OPG and sRANKL synthesis in osteoblasts to the application of CTS are regulated via the p38 MAPK pathway and suggest that CTS might modulate and regulate bone metabolism.

Prolactin: fishy tales of its primary regulator and function.

Prolactin (PRL) is an important regulator of multiple biological functions, and the control of PRL expression integrates a wide spectrum of molecules throughout vertebrates. PRL-releasing peptide (PrRP) seems to be an essential stimulator of PRL transcription and secretion in teleost pituitary and peripheral organs. In the amphibious euryhaline mudskipper, the localization of mRNA levels of PrRP and PRL as well as their regulation during acclimation to different environments are closely related. The presence of PrRP-PRL axes in the peripheral organs might suggest an ancient history of this axis prior to the evolution of the hypothalamus-pituitary, and it is possible that the PrRP is an original and primary regulator of PRL. In the euryhaline fishes, the permeability of gut of seawater-acclimated fish is generally greater than that of the freshwater (FW)-acclimated fish. The modification in the epithelial cell renewal system may play an important role in regulation of the permeability. PRL induces the cell proliferation during FW acclimation, whereas cortisol stimulates both cell proliferation and apoptosis. Indeed, a large proportion of the various actions of PRL seem to be associated directly or indirectly with cell proliferation and/or apoptosis, which might be a primary function of PRL.