齋藤 竹生

We conducted a retrospective study using medical records from Fujita Health University Hospital to evaluate the treatment discontinuation rates of suvorexant and lemborexant in patients with insomnia and to clarify differences in treatment acceptability. This study included patients newly prescribed suvorexant or lemborexant in the Department of Psychiatry between July 2020 and December 2022. The primary endpoint of the study was the discontinuation rate of suvorexant and lemborexant at 4 weeks. Discontinuation due to adverse events and lack of efficacy were assessed as secondary outcomes. The medical records of 1404 patients who were initiated on a dual orexin receptor antagonist during the study period were reviewed, and 1091 patients were included in the final analysis (suvorexant, 323; lemborexant, 768). We estimated the average treatment effect using the inverse probability of treatment weighting based on the propensity score. Discontinuation rates due to all-cause or adverse events did not differ significantly between the two drugs. However, the discontinuation rate due to lack of efficacy was significantly lower for lemborexant (4.9%; 38/768) compared to suvorexant (7.1%; 23/323), with an odds ratio of 0.63 (95% confidence interval, 0.48-0.83). This exploratory finding suggests a potential difference in treatment acceptability associated with efficacy between suvorexant and lemborexant in routine clinical practice, warranting further investigation.

Lifestyle diseases, such as obesity, diabetes, and metabolic syndrome, are leading health problems, most of which are related to abnormal lipid metabolism. Lysosomes can degrade lipid droplets (LDs) via microautophagy, but the regulatory factors and physiological significance of this process are not fully understood. Here, we report the molecular mechanism and pathophysiological roles of microlipophagy, regulated by the lysosomal membrane protein LAMP2B. Our study reveals that LAMP2B interacts with phosphatidic acid, facilitating lysosomal-LD interactions and enhancing lipid hydrolysis via microlipophagy depending on endosomal sorting complexes required for transport. Correlative light and electron microscopy demonstrates direct LD uptake into lysosomes at contact sites. Moreover, LAMP2B overexpression in mice prevents high-fat diet-induced obesity, insulin resistance, and adipose tissue inflammation; liver lipidomics analysis suggests enhanced triacylglycerol hydrolysis. Overall, the findings of this study elucidate the mechanism of microlipophagy, which could be promising for the treatment of obesity and related disorders.

Suicidal ideation (SI) and behavior (SB) are major public health concerns, but risk factors for their development and progression are poorly understood. We used ICD codes and a natural language processing algorithm to identify individuals in a hospital biobank with SI-only, SB, and controls without either. We compared the profiles of SB and SI-only patients to controls, and each other, using phenome-wide association studies (PheWAS) and polygenic risk scores (PRS). PheWAS identified many risk factors for SB and SI-only, plus specific psychiatric disorders which may be involved in progression from SI-only to SB. PRS for suicide attempt were only associated with SB, and even after accounting for psychiatric disorder PRS. SI PRS were only associated with SI-only, although not after accounting for psychiatric disorder PRS. These findings advance understanding of distinct genetic and clinical risk factors for SB and SI-only, which will aid in early detection and intervention efforts.