Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation–tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509.

Background: Examining the relationship between sleep and depression may be important for understanding the aetiology of affective disorders. Most studies that use electroencephalography (EEG) to objectively assess sleep have been conducted using polysomnography in the laboratory. Impaired sleep continuity, including prolonged sleep latency and changes in rapid eye movement (REM) sleep, have been reported to be associated with depression in clinical settings. Here, we aimed to use home EEG to analyse the association between sleep and depressive symptoms. Methods: We performed a cross-sectional epidemiological study in a large Japanese working population to identify the EEG parameters associated with depressive symptoms based on the results of a questionnaire survey and home EEG measurements using 1-channel (1-Ch) EEG. Results: The study included 650 Japanese patients (41.2% male, 44.7 ± 11.5 years) who underwent home EEG monitoring along with the Patient Health Questionnaire-9 (PHQ-9) to assess depressive symptoms. Logistic regression analysis revealed that depressive symptoms (PHQ-9 ≥ 10) were associated with sleep latency (odds ratio (OR) 1.02; 95% confidence interval (CI): 1.00–1.04) and REM latency (OR, 0.99; 95% CI: 0.99–1.00). Conclusions: Our results suggest that depressive symptoms are associated with prolonged sleep latency and reduced REM latency in a Japanese working population. The 1-Ch EEG may be a useful tool to monitor sleep and screen depression/depressive symptoms in non-clinical settings.

Study Objectives: Exploding head syndrome (EHS) is a parasomnia characterized by the perception of loud noises, or explosions inside the head during the sleep-to-wake transition. The prevalence of EHS remains unclear. This survey aimed to elucidate the prevalence of and factors associated with EHS in this cohort. Methods: As part of the Night in Japan Home Sleep Monitoring Study (NinjaSleep study), a cross-sectional survey was conducted among government employees in Koka City, Shiga Prefecture, Japan, in 2022. Participants were queried regarding their experiences with EHS as defined in the International Classification of Sleep Disorders, 3rd Edition, including sudden loud noises or sensations of explosions, subsequent abrupt awakenings and feelings of fright. Various standardized instruments were employed to evaluate depression, anxiety, insomnia, quality of life, and fatigue. Results: Of the 2081 employees invited to participate, 1878 completed the survey. After excluding respondents with epilepsy and incomplete responses, 1843 participants were deemed eligible for analysis. Among them, 46 (2.49%) reported experiencing sudden noises or sensations of explosions, with 23 (1.25%) meeting the diagnostic criteria for EHS. The EHS was significantly related to the scores on the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Athens insomnia scale, and Chalder fatigue scale, even after adjusting for age, sex, body mass index, and categorized mean sleep duration. Conclusion: This study elucidates the prevalence of EHS among the Japanese population and underscores its potential association with insomnia symptoms and various psychological factors.

Several hypotheses regarding the pathomechanisms of schizophrenia have been proposed. If schizophrenia is a unitary disease, then these pathological processes must be linked; however, if such links do not exist, schizophrenia may best be considered a group of disorders. Only a few studies have examined the relationships among these pathomechanisms. Herein, we examined the relationships among deficient myelination, NMDA receptor hypofunction, and metabolic dysregulation by measuring various plasma markers and examining their correlations. Plasma samples were collected from 90 patients with schizophrenia and 68 healthy controls. Concentrations of nardilysin (N-arginine dibasic convertase, NRDC), a positive regulator of myelination, the NMDA receptor co-agonist d-serine and glycine, various additional amino acids related to NMDA receptor transmission (glutamate, glutamine, and l-serine), and homocysteine (Hcy), were measured. Concentrations were compared using independent samples t-test or logistic regression, and associations were evaluated using Pearson's correlation coefficients. Plasma glycine (t = 2.05, p = 0.042), l-serine (t = 2.25, p = 0.027), and homocysteine (t = 3.71, p < 0.001) concentrations were significantly higher in patients with schizophrenia compared to those in healthy controls. Logistic regression models using age, sex, smoking status, glutamine, glutamate, glycine, l-serine, d-serine, homocysteine, and NRDC as independent variables revealed significantly lower plasma d-serine (p = 0.024) and NRDC (p = 0.028), but significantly higher l-serine (p = 0.024) and homocysteine (p = 0.001) in patients with schizophrenia. Several unique correlations were found between NMDA receptor-related amino acids and NRDC in patients with schizophrenia compared to those in healthy controls, while no correlations were found between plasma homocysteine and other markers. No associations were found between plasma marker concentrations and disease status or cognitive function in patients with schizophrenia, except for a significant correlation between plasma glycine and full intelligence quotient. Reduced myelination and NMDA receptor hypofunction may be related to pathological mechanisms in schizophrenia, while homocysteine dysregulation appears to be an independent pathological process. These results suggest that schizophrenia may be a group of disorders with unique or partially overlapping etiologies.