bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASSOCIATION BETWEEN MENTAL DISORDERS AND MORTALITY AMONG PATIENTS WITH COVID-19 IN SOUTH KOREA
Authors: Park *Subin 
Published: February 2025

Abstract

Background
This study investigated the association between mental disorder and mortality risk of those with COVID-19 patients. Specifically, the mortality risk of patients who were first diagnosed with mental disorders during the COVID-19 pandmic was considered.

Methods
The population-based cohort data from the National Health Insurance Service-COVID-19 database from Oct 2020 to Dec 2021 was utilized. The total patients were divided into three groups: 1) without mental disorder, 2) pre-existing mental disorder (i.e., History), and 3) first diagnosed with mental disorder during the COVID-19 pandmic (i.e., Pandemic onset). The primary outcome was all cause of mortality. Multivariable linear regression analysis was used to adjust for possible confounders.

Results
We included confirmed COVID-19 patients in the analysis (n=433,822). There were 352,473 patients (81.25%) without mental disorder group, 54,854 patients (12.64%) in the History group, and 26,495 patients (6.11%) in the Pandemic onset group. Overall, the all cuase of mortality rate was 0.71% (n=3,085). Compared to without mental disorder group, the History group was (AOR=1.42, 95% CI=1.30- 1.55) and Pandemic onset group (AOR=1.82, 95% CI=1.63-2.04) had a higher risk of mortality.

Discussion and Conclusion
We found that patients with mental disorders had a higher risk of mortality compared to those without mental disorders among patients with COVID-19. In particular, mortality is higher for patients who were first diagnosed with mental disorders during the COVID-19 pandemic.
THE IMPACT OF CHILDHOOD TRAUMAS ON RESPONSE TO ACCELERATED RTMS IN TREATMENT-RESISTANT DEPRESSION
Authors: D'andrea *Giacomo , Pettorruso Mauro , Mancusi Gianluca , Cavallotto Clara , Carullo Rosalba , Mosca Alessio , Carlo Francesco Di , Chiappini Stefania , Martinotti Giovanni 
Published: February 2025

Abstract

Background
Childhood traumas have long been recognized as pivotal determinants in the progression and severity of depressive disorders, especially in treatment-resistant depression (TRD). These early life adversities can induce distinct neurostructural and functional alterations, potentially mediating the responsiveness to antidepressant therapies.

Aims & Objectives
To evaluate the interplay between childhood traumas and treatment outcomes in TRD patients undergoing an accelerated repetitive transcranial magnetic stimulation (arTMS) regimen.

Methods
In this multicentric, prospective analysis, we enrolled 51 TRD patients (average age 56±13.305; M/F=28/23) involved in an intensive arTMS protocol— comprising 4 daily sessions over 5 consecutive days, targeting the Left Dorsolateral Prefrontal Cortex at High Frequency/10 Hz. Comprehensive psychiatric evaluations were performed, employing the MADRS scale to chronicle depressive symptoms at various stages (baseline/T0, one week/T1, and a month/T2 post-treatment) and the CTQ scale (at T0) to quantify exposure to traumas during early life. CTQ scores guided the bifurcation of patients into two cohorts: those minimally exposed to childhood traumas (Low_Trauma) and their highly exposed counterparts (High_Trauma). We developed a General Linear Model (GLM), implementing repeated measures ANOVA (rm-ANOVA), to discern the interplay between temporal shifts (T0vsT1vsT2) and trauma exposure groups.

Results
Our rm-ANOVA underscored a marked improvement in MADRS scores from T0 through T1 to T2 (F98,2=73.938; P&lt;0.001), attesting the robust efficacy of the arTMS modality. Intriguingly, there emerged a pronounced interaction between the temporal trajectory and trauma exposure groups (Low_trauma vs. High_Trauma) (F98,2=5.980; P=0.004). Subsequent analyses elucidated a more pronounced symptom amelioration in the Low_Trauma cohort. Notably, the comparative efficacy was markedly elevated in the group with lesser traumatic experiences (Cohen’ s d: 2.164 vs. 1.204), underscoring the potential inhibitory role of extensive childhood trauma on therapeutic outcomes.

Discussion & Conclusions
Early-life traumatic events seemingly interface with distinct neural networks, potentially resistant to modulation by the arTMS protocol. Such profound traumas during formative years could thus emerge as a harbinger of suboptimal treatment outcomes. A deeper exploration into TMS's neurophysiological dynamics and trauma's psychobiological underpinnings might pave the way for a better therapeutic approach, clinically-oriented, for TRD patients.
THE MEDIATING EFFECTS OF WORKING HOURS, SLEEP DURATION, AND DEPRESSIVE MOOD ON THE ASSOCIATION BETWEEN SHIFT WORK AND THE RISK OF SUICIDAL IDEATION IN KOREAN WORKERS
Authors: Park Mina , Ho *Dham , Lim Weon-Jeong 
Published: February 2025

Abstract

Aims & Objectives
This study aimed to investigate the mediation effects of working hours, sleep duration, and depressive mood on the association between shift work and the risk of suicidal ideation in Korean workers.

Method
Data from 33,047 workers were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys conducted in 2007–2018. Healthy workers without depressive disorders and chronic medical illnesses were included in the current study. Shift work patterns, sleep duration, working hours, depressive mood, and suicidal ideation were assessed using self-reported questionnaires. Multivariate logistic regressions were used to examine the association between shift work and the risk of suicidal ideation. Additionally, mediating studies were conducted to identify the roles of working hours and sleep durations on the association.

Results
Compared with daytime workers, shift workers had 1.33 times greater risk of suicidal ideation (OR=1.33, 95% Cl = 1.17-1.52, p &lt;0.001). Specifically, among shift work patterns, fixed-night shift, 24-hours rotating shift and irregular rotating shift was associated with the risk of suicidal ideation than daytime workers (irregular rotating shift: OR= 1.92, 95% Cl = 1.29-2.86, p =0.001; fixed-night shift: OR= 1.75, 95% Cl= 1.32-2.31, p &lt;0.001; 24- hours rotating shift: OR= 1.58, 95% Cl= 1.06-2.36, p= 0.024). In the mediating study, working hours, sleep duration and depressive mood significantly mediated the relationship between shift work and suicidal ideation (direct effect: β=0.019, p=0.001; indirect effect: β=0.004, p=0.031; total effect: β=0.023, p&lt;0.001).

Discussion & Conclusion
This study revealed that shift workers had a greater risk of suicidal ideation. The patterns significantly associated with suicidal ideation were irregular rotating, fixed-night, and 24- h rotating shifts. The pathway analysis revealed serial mediating effects of working hours, sleep duration, and depressive mood on the association between shift work and suicidal ideation.
KNOCKDOWN OF CONNEXIN43 POTENTIATES ANTIDEPRESSANT EFFECT ON BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION IN PRIMARY CULTURED ASTROCYTES
Authors: Tokunaga *Nozomi , Nakamura Yoki , Hisaoka-Nakahsima Kazue , Morioka Norimitsu 
Published: February 2025

Abstract

Background
The number of depression patients is increasing, which is one of the society problems in the world. In general, antidepressants affect through the increase of monoamine concentration at synaptic cleft. Although antidepressants upregulate monoamine level immediately after administration, several months are required for the manifestation of antidepressant effect in patients of depression, suggesting the other mechanism which is independent with monoamine. Moreover, the therapeutic satisfaction is very low because antidepressant drugs are not effective for one-third of patients and the most appropriate drug for each patient is different. Therefore, the development of biomarker to assess the efficacy of antidepressants is needed. Connexin43 (Cx43) is highly expressed in astrocytes, which is the most abundant glia cells in the brain, and contributes to not only intercellular molecular transportation but also intracellular signaling. It is demonstrated that Cx43 expression is reduced in the prefrontal cortex and hippocampus of depressive patients, suggesting that Cx43 may be involved in the pathology of depression. Our previous study showed that Cx43 expression in hippocampus was negatively correlated with the antidepressant effect of amitriptyline in the depressive model mice. In addition, we demonstrated that amitriptyline increases brain-derived neurotrophic factor (BDNF) expression in primary cultured astrocytes. However, the significance of Cx43 reduction for the antidepressant effect and the influence of Cx43 downregulation for BDNF expression by antidepressant drug in the astrocytes are still uncovered.

Aims & Objectives
The current study examined whether amitriptyline potentiates BDNF expression in astrocytes with reduced Cx43 expression, and the mechanism of this potentiation.

Method
Primary cultured astrocytes were prepared from the cerebral cortex of neonatal Wistar rats. The expression of Cx43 was downregulated by RNA interference. The expression of mRNA and protein were measured by real-time PCR and western blotting, respectively.

Results
Downregulation of Cx43 potentiated the amitriptyline-induced BDNF expression in cultured astrocytes. This potentiation was significantly suppressed by the blockade of LPA1/3 receptors, Src tyrosine kinase, and extracellular signal-regulated kinase (ERK).

Discussion & Conclusion
The current study revealed that reduced Cx43 expression potentiates the amitriptyline-induced BDNF expression in cortical astrocytes. In addition, LPA1/3-mediated Src-ERK signaling is crucial in the potentiation of amitriptyline-induced BDNF expression in Cx43-downregulated astrocytes. These results indicate the downregulation of Cx43 observed in the depressive patients might contribute to therapeutic effect of antidepressants.
FACTORS INFLUENCING SUBJECTIVE MEMORY COMPLAINTS AMONG COMMUNITY DWELLING ELDERLY IN URBAN COMMUNITY
Authors: Lee *Kyoung Hwan 
Published: February 2025

Abstract

Background
There are many factors influence subjective memory complaints including neurocognitive disorder, mood disorder and anxiety disorder.

Aims & Objectives
We examined the factors influencing subjective memory complaints among community dwelling elderly in urban area.

Method
The subjects of this research were 160 community-dwelling elderly people without dementia and major depressive disorder. The questionnaires regarding the socio-demographic characteristics were conducted by each person. They include Korean version of Subjective Memory Complaints Questionnaires (SMCQ), Korean version of Short Geriatric Depression Scale (SGDS-K) and Korean version of Mini-Mental State Examination (K-MMSE). Subjective memory complaints were defined as above 4 points of SMCQ.

Results
39.38% of the subjects had subjective memory complaints. There were significant associations between subjective memory complaints and SGDS-K (p&lt;0.001), physical illness (p=0.001), but there was no association with K-MMSE (p=0.383).

Discussion & Conclusion
There is a discrepancy between subjective memory complaints and actual cognitive impairments. This discrepancy suggests that the depressive disorders including minor depressive disorder and subsyndromal depression, might play a role in the subjective memory complaints rather than actual cognitive impairments in community-dwelling elderly people. Therefore, the treatments for the depressive disorders should be considered in dealing with the subjective memory complaints.
AN OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TREATMENT WITH LEMBOREXANT IN SUBJECTS WITH CHRONIC INSOMNIA (SOMNUS STUDY)
Authors: Ozone *Motohiro , Hirota Susumu , Ariyoshi Yu , Hayashida Kenichi , Ikegami Azusa , Habukawa Mitsunari , Ohshima Hayato , Harada Daisuke , Hiejima Hiroshi , Kotorii Nozomu , Murotani Kenta , Taninaga Takehiro , Uchimura Naohisa 
Published: February 2025

Abstract

Background
Effective alternative therapies are needed to improve outcomes in the treatment of insomnia disorder due to concerns regarding the risks of tolerance, dependence, falls and withdrawal syndrome with the use of pharmacological treatments such as benzodiazepine-receptor agonists (BZRA). Lemborexant (LEM), a competitive dual orexin-receptor antagonist approved in Japan and other countries to treat adults with insomnia, has shown superior therapeutic efficacy to zolpidem extended-release 6.25 mg in a phase 3 clinical trial; therefore, LEM may be a potential alternative candidate.

Aims & Objectives
To evaluate whether the approach of a direct transition to LEM either from a Z-drug (zolpidem, zopiclone, or eszopiclone) or suvorexant (SUV) monotherapy or from SUV or BZRA and ramelteon (RMT) combination therapy can be supported for patients with insomnia.

Methods
A prospective, nonrandomized, open-label, multicenter study conducted in Japan with 90 subjects with chronic insomnia dissatisfied with current treatment was designed to investigate whether direct transition to LEM improved patient satisfaction. The study was comprised of four cohorts: (1) nonbenzodiazepine sedative-hypnotic (Z-drug) monotherapy, (2) orexin receptor antagonist (SUV) monotherapy, (3) SUV plus BZRA combination therapy, and (4) melatonin receptor agonist (RMT) plus BZRA combination therapy. The primary outcomes were continuation of treatment after 2 weeks (end of titration phase) and 14 weeks (titration phase and maintenance phase), as well as responses on the Patient Global Impression – Insomnia version (PGI-I) and Insomnia Severity Index (ISI) scales. Subjects in the BZRA combination therapy groups could attempt, but were not required, to decrease BZRA use during the maintenance phase. This study was approved by the Certified Clinical Research Review Board, and informed consent was obtained.

Results
In all, 95.6% (n=86/90) successfully transitioned to LEM after 2 weeks, and LEM continuation rates were 97.8% (n=88/90) at the completion of the titration phase and 82.2% (n=74/90) at the completion of the maintenance phases. At 14 weeks, dose reduction and interruption of BZRA occurred in 12.5% (n=4/32) of the combined cohort. In the entire cohort, PGI-I scores showed a greater percentage of positive responses than negative responses. ISI total scores also improved over time after the transition to LEM. The overall incidence of adverse events was 47.8% (n=43/90) and none were serious.

Discussion & Conclusion
These findings suggest that direct transition to LEM is a valid treatment option for insomnia in patients who are dissatisfied with their current treatment.

Support
Eisai, Ltd.
CHRONIC SLEEP FRAGMENTATION ACCELERATES THE DEVELOPMENT OF PRODROMAL SYMPTOMS AND PATHOLOGICAL CHANGES IN PARKINSON’ S DISEASE MODEL MICE
Authors: Miyazaki *Masayuki , Yagihara Hiroko , Fujita Hiromi , Yamakado Hodaka , Wada Keiji , Minakawa Eiko N 
Published: February 2025

Abstract

Background
Parkinson’ s disease (PD) is the second most common neurodegenerative disease after Alzheimer’ s disease. Patients with PD exhibit various non-motor symptoms, including constipation, hyposmia, and sleep disturbance, in addition to classical motor symptoms such as bradykinesia, muscular rigidity, and rest tremor. The pathological hallmarks of PD are phosphorylated alpha-synuclein (p-syn) accumulation and dopaminergic neuronal loss in substantia nigra pars compacta. Patients are generally diagnosed with PD after the onset of motor symptoms, but the onset of non-motor symptoms often precedes that of motor symptoms. This prodromal phase of PD, which lasts for more than a decade, is a critical time window for disease modification to prevent or delay the onset of motor symptoms. Insomnia is the most common sleep disorder in older adults and patients with PD. In patients with PD, chronic sleep fragmentation due to frequent nocturnal arousals is the most prevalent symptom of insomnia. While various PD-related etiologies induce chronic sleep fragmentation, recent epidemiological studies suggested that chronic sleep fragmentation itself may accelerate the clinical and pathological progression of PD. However, the precise causal relationship between progression of PD and chronic sleep fragmentation remains unknown.

Aims & Objectives
We aimed to test whether chronic sleep fragmentation accelerates the disease course of PD using model mice.

Method
Transgenic mouse model of PD (Tg) that recapitulates age-dependent onset and progression of premotor non-motor symptoms, or wild type (WT) mice were housed in either of the following cages from the age when Tg mice do not exhibit non-motor symptoms: (1) sleep disturbance (SD) cage, a running- wheel-based device that induces chronic sleep fragmentation similar to PD patients (SD group), (2) wheel cage (WC), a control cage with a running wheel but with no sleep disruption (WC group), or (3) normal cage (NC), another control cage without running wheel (NC group). After 5 or 6 weeks, multiple non- motor symptoms were evaluated. After 7 weeks, brains were collected, and p-syn accumulation in the brains of Tg mice was evaluated.

Results
Among Tg mice, only the SD group showed non-motor symptoms. Among WT mice, the SD group showed no or minimal non-motor symptoms which were milder than that of Tg mice in the SD group. Among Tg mice, the SD group showed significantly increased p-syn accumulation in multiple brain regions.

Discussion & Conclusion
These results suggest that chronic sleep fragmentation accelerates the onset of prodromal symptoms and p-syn accumulation in PD model mice. Our findings implicate that chronic sleep fragmentation would be a potential target for preventing or delaying the motor onset of PD.
A BRIEF SELF-COMPASSION AND SELF-ESTEEM INTERVENTION FOR SUICIDAL UNIVERSITY STUDENTS: A FEASIBILITY STUDY
Authors: Nguyen *Dat Tan , Mitsui Nobuyuki , Satoshi Asakura , Fujii Yutaka , Toyoshima Kuniyoshi , Kusumi Ichiro 
Published: February 2025

Abstract

Objectives
Suicide is a serious mental health problem among university students. The current study aimed to examine the effectiveness of a novel psychological education program targets suicidal ideation by enhancing self-esteem and self-compassion.

Methods
A single-arm study design was implemented to investigate the feasibility and acceptability of a novel four-session psychoeducation program for university students who experienced suicidal ideation. The study protocol was registered retrospectively in the national UMIN Clinical Trials Registry (Registration ID: UMIN000043702) and approved by Hokkaido University Ethical Committee (Approval ID: 20-031). Recruitment took place from Hokkaido university health care center. Suicidal behaviors, self- compassion, self-esteem, and other psychological variables were measured at baseline, post- intervention, and 1-month follow-up. Participants also completed an evaluation of the program’ s acceptability.

Results
Currently, twelve participants consented to take part in the intervention with nine participants completed post treatment assessments. The attrition rate was 25%. There was a significant reduction for depression (Cohen’ s d = 1.198) and suicidal behaviors (Cohen’ s d = 0.891) as well as a significant increase for self-compassion (Cohen’ s d =1.352) at post-intervention. Additionally, the psychoeducation program was highly appreciated and positively received by the participants.

Discussion
The study showed promising result for the psychoeducation program, especially in terms of reducing suicidal ideation and depression. However, the study suffers from a small sample size with a single-arm study design. Further study regarding the effectiveness of the program is highly warranted.
THE EFFICACY OF LACOSAMIDE AND PERAMPANEL IN THE ANIMAL MODEL OF AUTISM SPECTRUM DISORDER
Authors: Matsuoka *Satomi , Moriya Yuka , Ito Fuyuka , Miyachi Mai , Fuwa Takemi , Kurahashi Hitomi , Nabeshima Toshitaka , Mouri Akihiro , Hasegawa Yoichi 
Published: February 2025

Abstract

Background
Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by social deficits and restrictive patterns of behavior and interests. Epilepsy is comorbidity in ASD patients. The imbalance of excitation and inhibition in neural circuitry is hypothesized for the pathophysiology of ASD as well as epilepsy. It is epidemiologically reported that administration of valproic acid (VPA) during pregnancy increases the risk of ASD in the offspring. In this study, we investigated therapeutic potential of anti-epileptic drugs for ASD using prenatal VPA-induced ASD animal model.

Methods
Pregnant mice were injected with VPA (500 mg/kg, i.p.) on gestational day 12. The offspring were subjected social interaction test, novel object recognition and repetitive behavior test. The offspring were injected with anti-epileptic drugs (lacosamide, and perampanel) before each behavioral test.

Result
The offsprings from mice exposed to VPA during pregnancy showed decrease in social interaction time and exploratory preference for novel object, and increase in grooming numbers. The lacosamide, and perampanel increased exploratory preference for novel object and decreased grooming numbers in the offsprings from mice exposed to VPA during pregnancy.

Conclusion
Behavioral changes in offsprings from mice exposed to VPA during pregnancy are associated with the symptom of ASD (decrease in social interaction time: social disability, decrease in approach time for novel object: cognitive dysfunction). We suggest that lacosamide and perampanel improve visual recognition memory impairment and increased repetitive behavior in ASD model mice. These data suggested that anti-epileptic drugs attenuated could have therapeutic potential for ASD symptoms.