bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE INVOLVEMENT OF SPLENIC IMMUNE CELLS IN THE DEPRESSION-LIKE BEHAVIORS INDUCED BY CHRONIC SOCIAL DEFEAT STRESS
Authors: Ogawa *Moeka , Kunisawa Kazuo , Kosuge Aika , Tezuka Hiroyuki , Nabeshima Toshitaka , Mouri Akihiro 
Published: February 2025

Abstract

Background
Accumulating evidences suggest a substantial role of enhanced inflammatory responses in the pathophysiology of major depressive disorder (MDD). The spleen, a pivotal organ in the immune response, may play a role in the enhanced inflammatory responses of MDD. Chronic social defeat stress (CSDS) is well established to develop an animal model of MDD.

Aims & Objectives
In the present study, we investigated the involvement of the spleen in the CSDS-induced depression-like behaviors in mouse.

Method
In the CSDS, the adult C57BL/6J mouse was exposed to an aggressor ICR mouse for 10 consecutive days.

Results
CSDS effectively reduced the social interaction (SI) ratios in the social interaction test (SIT) and the time spent in the open arms in the elevated plus maze test (EPM) in C57BL/6J mouse. A remarkable observation was the significant increase in the spleen weight following CSDS, suggesting enhanced inflammatory response in the splenic immune cells. Splenectomy ameliorated the CSDS-induced social impairment in the SIT but not anxiety-like behavior in the EPM. CSDS elevated the levels of noradrenaline (NA) in the spleen. Interestingly, CSDS reduced the adrenergic β2 receptors, primarily localized on CD4+ T cells. Flow cytometry analysis revealed that CSDS decreased CD4+ T cells, but increased CD11b+Ly6C+ monocytes in the spleen. Antidepressant treatment significantly ameliorated the increase of CD11b+ Ly6C+ monocytes and social impairment induced by CSDS.
Discussion&Conclusion: These findings provide insights into the role of splenic immune cells in depressive-like behavior induced by CSDS. Furthermore, our results suggest that a decreased noradrenergic anti-inflammatory pathway may be implicated in the depression-like behavior induced by CSDS.
METHYLONE PRODUCES ANTIDEPRESSANT-RELEVANT ACTIONS AND PROSOCIAL EFFECTS
Authors: Li Zhenlong , Peng Hsien-Yu , Lee Chau-Shoun , Lin Tzer-Bin , Hsieh Ming-Chun , Lai Cheng-Yuan , Wu Han- Fang , Chen Lih-Chyang , Chen Mei-Ci , Chou *Dylan 
Published: February 2025

Abstract

Background
Methylone (3,4-methylenedioxy-N-methylcathinone) is a rapid-acting entactogen that has been shown to have significant benefits in patients with post-traumatic stress disorder and major depressive disorder and is well tolerated in phase 1 clinical trials. A recent preclinical study reported that methylone produced robust antidepressant-like actions in naï ve rats. However, its antidepressant effects on various stress-related psychopathologies and other neuropsychological actions remain unclear.

Aims & Objectives
In the present study, we examined the antidepressant-relevant effects of methylone in learned helplessness (LH) and social defeat stress C57BL/6J male mouse models and further explored its sociability-relevant neuropsychological actions.

Methods
Tail suspension test, female urine sniffing test, sucrose preference test, social interaction test, three-chamber test, social behavior test, observed fear conditioning, helping behavior, and electrophysiological recording were used.

Results
Our results indicate that methylone produces antidepressant-relevant effects on the helpless phenotype, LH-evoked depressive-like behaviors, and psychosocial stress-induced social avoidance, and induced depressive-like behaviors. In addition, methylone was found to enhance social preference and increase various social behaviors, including social contact, sniffing, allogrooming, and following. Moreover, methylone appeared to elevate empathy-like phenotypes and was also found to increase helping-like behavior.

Discussion & Conclusion
Overall, the present results suggest that methylone plays an antidepressant-like role in various stress-relevant psychopathologies and could be an ideal antidepressant candidate. In addition, novel findings on the elevated tendencies of social preference and empathy-like and helping-like phenotypes reveal that methylone may have potential application in patients with social deficits.
CLINICAL VALUE OF PLASMA SOLUBLE TREM2 IN IDENTIFYING MILD COGNITIVE IMPAIRMENT: A COMMUNITY-BASED STUDY OF THE CHINESE ELDERLY
Authors: Huang Anqi , Wang *Lan 
Published: February 2025

Abstract

Objectives
To clarify that correlation in plasma soluble TREM2 (sTREM2) and cognitive function between mild cognitive impairment (MCI) and normal cognitive function in a Chinese community population, and further to explore whether plasma sTREM2 can be used as a blood biomarker to predict and identify MCI.

Methods
This study included 216 community elderly people in Shijiazhuang and Xingtai City, Hebei Province, including 106 MCI and 110 normal cognitive function (NC) subjects. The Montreal cognitive assessment (MoCA) was used, mini mental state examination (MMSE), Boston naming test (BNT), digit span test (DST) to evaluate the cognitive functions of all subjects. Fasting venous blood was collected at the same time, and ELISA was used to detect Aβ42, Aβ40, P-Tau217, P-Tau231, TREM2, sTREM2 concentration. Use software based on SPSS 26.0 to analyze the data.

Results
1. The level of sTREM2 in the MCI group was higher than that in NC group, and the difference was statistically significant (H=4312.0, P=0.001). There was no statistical significance in the difference of the other index between two groups (P&gt;0.05). 2.Correlation analysis showed that sTREM2 was negatively correlated with P-tau217, education level, MMSE, MoCA, BNT, and DST (P&lt;0.05). TREM2 was positively correlated with P-tau217 and Aβ42 (P&lt;0.05). 3. Incorporate whether it was MCI as the dependent variable, gender, age, education level, living style, and the above blood indicators as independent variables in binary logistic regression analysis. The results showed that sTREM2 was a risk factor for MCI (OR=1.009, 95%CI=1.002-1.016, P=0.015), junior high school education or above was a protective factor for MCI (OR=6.133, 95 % CI=2.651-14.189, P&lt;0.001). 4.The area under the ROC curve of sTREM2 was 0.630 (sensitivity 0.472, specificity 0.782), and the area under the ROC curve of sTREM2 combined with MMSE was 0.849 (sensitivity 0.679, specificity 0.873).

Conclusion
sTREM2 is a risk factor for cognitive function decline in MCI. Plasma sTREM2 levels combined with the cognitive function assessment scale have good clinical value in identifying mild cognitive impairment.
BARRIERS TO AND FACILITATORS OF USER ENGAGEMENT WITH PSYCHOLOGICAL FIRST AID CHATBOT INTERVENTION: FEASIBILITY STUDY
Authors: Frankova *Iryna , Lahutina Sofiia 
Published: February 2025

Abstract

Background
Full-scale war of aggression upon Ukraine (February 2022 – ongoing) has affected millions of people (Poberezhets, 2022). Violence, forced displacement, participation in hostilities, loss of loved ones during military conflicts can directly increase the risk of mental disorders, namely post-traumatic stress disorder, depression and anxiety disorders, as well as significantly reduce the quality of life of victims (Grasser, 2022; Bü rgin et al., 2022). Psychological first aid (PFA) involves the provision of immediate support to survivors of violence and trauma in order to reduce stress, alleviate suffering and accelerate recovery (Figueroa et al., 2022). At the same time, the timing of providing PFA after exposure to a traumatic event plays an important role (Vermetten et al., 2020).The digital format of providing PFA can provide rapid, affordable, scalable and effective solution during war, when there is a limited mental health resources, including insufficient numbers of trained professionals, infrastructural gaps, and financial constraints (Mahmoud et al., 2022).

Aim
to assess the feasibility of a digital PFA micro intervention in chatbot during the golden hours and first months for the adult population of Ukraine affected by the war.

Methods
thematic analysis of users` feedback.

Results
a total of 102,391 activated "Friend" PFA chatbot from the 1st of March 2022 to the 1st October 2023. The specifics of using a chatbot have been carried out through a detailed analysis of qualitative and quantitative users` feedback. 2,207 users were surveyed, most of whom (45.2%) gave it an “Excellent” rating, while another significant portion (39.3%) rated the bot as “Fair”. 9.3% of users rated the bot "Bad", 6.2% saw it as "Terrible". 1,557 written feedback were qualified as valuable reviews that were subjected to qualitative analysis. Factors extracted for coding were related to the end user, the program or content offered by the intervention, and the technology and implementation environment. Common barriers included severe mental health issues that hampered engagement, technical issues, and a lack of personalization. Common facilitators were social connectedness facilitated by the intervention, increased insight into health, and a feeling of being in control of one’ s own health.

Discussion And Conclusion
User feedback analysis has been integrated to optimize and personalize the service. Conducting a feasibility study of user engagement with a digital tool is a proactive approach to ensure that the tool meets its intended purpose, resonates with the target audience, and provides a positive return on investment. It allows to make data-driven decisions, mitigate risks, and optimize the tool's design and functionality to enhance engagement and overall success.
CLINICAL UTILITY OF IMPACT OF EVENT-SCALE-REVISED FOR DSM-5 POSTTRAUMATIC STRESS DISORDER
Authors: Chang So-Yeon , Joo *Yonghee , Bae Jeong-Hoon , Kim Won-Hyoung , Park Joo-Eon 
Published: February 2025

Abstract

Background
The Impact of Event Scale-Revised (IES-R) is one of the most widely used self-report measures of post-traumatic stress disorder (PTSD), though it was based on the DSM-IV Diagnostic criteria.1 The previous studies have suggested a cutoff point of the IES-R according to DSM-IV.2

Aims & Objectives
The aim of this study is to investigate whether the IES-R is applicable within the DSM-5 nomenclature and to determine the cutoff point for DSM-5 PTSD diagnosis.

Methods
A total of 238 subjects, recruited from multiple psychiatric centers, participated in this study, including 67 with PTSD, 72 with psychiatric controls, and 99 with healthy controls. All subjects completed the Korean version of the structured clinical interview for DSM-5 Research Version to confirm the presence of PTSD, the Korean version of the PTSD checklist for DSM-5 (K-PCL-5), the Beck Depression Inventory-II (BDI-II), the Beck Anxiety Inventory (BAI), and the Spielberger State Trait Anxiety Inventory.

Results
The IES-R presented good internal consistency (Cronbach's α = 0.95). The IES-R was correlated highly with K-PCL-5. Factor analysis identified five factors in the IES-R, which we labeled as intrusion, avoidance, hyperarousal, sleep disturbance, and numbness-dissociation. The suggested cutoff score for PTSD was 25 of the IES-R with a sensitivity of 86.57 and a specificity of 82.46.

Discussion & Conclusion
These results demonstrated the good concurrent validity with current DSM-5 PTSD scale and adequate diagnostic utility for screening current DSM-5 PTSD. This study suggests that a cutoff score of 25 on the IES-R should be considered when the scale is used to screen for DSM-5 PTSD diagnosisa

References
1)Weiss, DS 2007, Cross-Cultural Assessment of Psychological Trauma and PTSD, Springer, Boston, MA. Eun H-J 2005, 2) A study on reliability and validity of the Korean version of impact of event scale-revised, J Korean Neuropsychiatr Assoc, 44(3), pp. 303–310.
CELL TYPE-SPECIFIC TRANSCRIPTIONAL CHANGES FOLLOWING CHRONIC TREATMENT OF CLOZAPINE IN MOUSE PREFRONTAL CORTEX
Authors: Park Kyungtaek , Kang Nuree , Huh Seong-Hoo , Won Sungho , Kim *Se Hyun 
Published: February 2025

Abstract

Background
Schizophrenia is a major psychotic disorder with complex genetic underpinnings. Clozapine is one of the representative antipsychotics for its unique and superior efficacy. The current understandings of clozapine’ s mechanism do not fully explain the favorable therapeutic properties of clozapine, in which the differential gene activation related to the pathophysiology of schizophrenia may be involved. Therefore, studying the transcriptomic changes induced by clozapine could contribute to the advancement of schizophrenia treatments.

Aims & Objectives
We aimed to investigate cell type-specific clozapine-induced transcriptional changes in mouse prefrontal cortex through single-cell RNA sequencing (scRNA-seq). The goal of this study was to provide important insights into the mechanism of action of clozapine and examine its associations with genes related to the etiology of schizophrenia.

Method
In this study, clozapine was systemically injected into male C58BL/6 mice for 21 consecutive days, and single-cell RNA sequencing was applied to their prefrontal cortical tissue samples. Differentially expressed genes (DEGs) for each cell type, including microglia, astrocytes, neurons, endothelial cells, and vascular smooth muscle cells, were identified through single-cell RNA sequencing. Pathways and intercellular interactions associated with these DEGs were then analyzed. Additionally, a comparative analysis with human databases was conducted, using the toxicogenomics database (CTD), genetic loci implicated in schizophrenia, and genes with evidence of interaction with clozapine.

Results
Clozapine-induced changes in gene expression were most prominent in microglia, and the cell population clusters within microglia were altered by clozapine exposure. Pathway analyses highlighted TNF-α signaling via NF-κ B, IFN-γ response, IFN-α response, and p53 pathway as particularly engaged by clozapine. Cell-cell interaction analysis demonstrated the clozapine-induced interactive changes among microglia, endothelial cells, and vascular smooth muscle cells. Comparative analysis with human data also revealed enriched clozapine-induced DEGs in microglia. As a result, eleven genes, including Nfkb1, Nfe2l2, Egr1, Fos, and Atp6v1b2, were elucidated to have convergent evidence.

Discussion & Conclusion
By using scRNA-seq, we identified discrete cell types and their alterations in the mouse prefrontal cortex. While microglia are mainly impacted by clozapine exposure, other cell types also display distinct changes. Single-cell RNA sequencing could provide important insights into the mechanisms of action of clozapine, a representative antipsychotic with superior efficacy, which has links to the genetic background of pathogenetic and therapeutic mechanisms in schizophrenia.
ASSOCIATIONS BETWEEN NEUROMELANIN ACCUMULATION IN PATIENTS WITH SCHIZOPHRENIA AND TREATMENT RESPONSIVENESS: A CROSS- SECTIONAL NM-MRI STUDY
Authors: Ueno *Fumihiko , Iwata Yusuke , Honda Shiori , Horga Guillermo , Cassidy Clifford M , Torres-Carmona Edgardo , Song Jianmeng , De Luca Vincenzo , Tsugawa Sakiko , Noda Yoshihiro , Agarwal Mahavir , Gerretsen Philip , Nakajima Shinichiro , Graff-Guerrero Ariel 
Published: February 2025

Abstract

Background
Neuromelanin (NM) is a byproduct of monoamine metabolism, including that of dopamine. NM-sensitive Magnetic Resonance Imaging (NM-MRI) sequences enable the in vivo quantification of NM levels in the substantia nigra (SN). The NM-MRI signal is considered a surrogate marker for the integrity of SN dopamine neurons and, consequently, striatal dopaminergic functioning. Elevated striatal dopamine synthesis is associated with patients responsive to first-line antipsychotics (FLR) in schizophrenia, while normal striatal dopamine synthesis is implicated in the pathophysiology of treatment-resistant schizophrenia (TRS). Clozapine is the only antipsychotic currently approved for TRS. However, no studies have yet explored the relationship between SN accumulations, as measured by NM-MRI, and clozapine response in TRS patients.

Aims & Objectives
The study aims to investigate differences in dopaminergic activities among schizophrenia patients based on their treatment response, using NM-MRI.

Methods
The study enrolled TRS patients who either did not respond to clozapine (ultra-resistant schizophrenia [URS]) or did respond (non-URS), along with FLR patients and healthy controls (HCs). TRS was defined as resistance to at least two first-line antipsychotics and ongoing clozapine treatment at the time of the study. SN-NM levels were measured using 3T-MRI. The Contrast Ratio (CR) was calculated as the relative signal intensity difference between the SN and the crus cerebri. SN-CR values were compared between groups, controlling for age and sex. Associations between SN-CR and symptom severity scores were also explored within patient groups.

Results
A total of 78 participants (URS: n=16; non-URS: n=16; FLR: n=20; HCs: n=26) completed the study. Overall group differences in SN-CR values were significant (F(3,72)=3.80, η2=0.21, p=0.001). Specifically, URS patients (Cohen’ s d=0.86, p=0.049) and FLR patients (Cohen’ s d=1.27, p&lt;0.0001) exhibited higher SN-CR values compared to HCs. No associations were found between SN-CR values and symptom severity scores within each group or the entire patient cohort.

Discussion & Conclusion
This study is the first to assess a proxy measure of mesostriatal dopamine function in schizophrenia patients, stratified by treatment responsiveness, using NM-MRI. We observed elevated SN-NM contrast in URS and FLR patients compared to HCs, and levels similar to HCs in non-URS patients. Longitudinal studies are warranted to determine whether SN-NM levels can serve as a reliable biomarker for predicting treatment response in schizophrenia.
SAFETY AND EFFICACY OF LEMBOREXANT IN PATIENTS WITH INSOMNIA DISORDER: REPORT FROM A POST-MARKETING OBSERVATIONAL STUDY
Authors: Mishima *Kazuo , Fujimoto Kenichi , Endo Akira , Ishi Mika 
Published: February 2025

Abstract

Background
The competitive dual orexin receptor antagonist lemborexant (LEM) has been available in Japan as a treatment for insomnia since July 2020. The most commonly reported adverse event (AE) in phase 3 studies was somnolence. A post-marketing observational study (E2006-M081-501) was conducted to examine the incidence of adverse drug reactions (ADRs) in daily clinical practice.

Aims & Objectives
To report the incidence of somnolence, nightmares, abnormal dreams, sleep paralysis, hypnotic hallucinations, suicidal ideation, and suicidal behavior in patients with insomnia disorder during treatment with LEM in daily clinical practice.

Methods
The enrollment period was from October 1, 2020 to September 30, 2021 with an observation period of 24 weeks. Informed consent was obtained from all subjects participating in the survey. Survey items included patient characteristics (eg, age, prior medication), incidence of AEs, overall improvement, and ADRs. The incidence rates of AEs and percentage of subjects demonstrating global improvement were calculated.

Results
The survey was conducted at 170 sites in 539 subjects. Among the 510 subjects included in the safety analysis, there were 210 males and 300 females; the mean age was 53.7 years and the proportion of subjects aged at least 65 years was 32.9%. The incidence of ADRs was somnolence 7.65% (39/510), nightmares 1.76% (9/510), abnormal dreams 0.59% (3/510), and sleep paralysis 0.20% (1/510). ADR incidence in this survey was similar to that reported in phase 3 studies. There were no ADRs related to hypnotic hallucinations, suicidal ideation, or suicidal behavior. The rate of global improvement in symptoms was 80.83% (371/459), excluding cases in which the evaluation time of global improvement was outside the acceptable range, the evaluation date was unknown, or a determination of improvement could not be made.

Discussion & Conclusion
The safety profile found in this analysis was comparable to that described in the LEM prescribing information, and the efficacy profile supports the clinical utility of LEM in the treatment of insomnia disorder.

Support
Eisai Co., Ltd.
CLINICAL EPIDEMIOLOGY OF THE EFFECT OF NOVEL HYPNOTICS ON PRESCRIBING CHANGES IN PATIENTS USING BENZODIAZEPINE RECEPTOR AGONISTS
Authors: Ayani *Nobutaka John , Kurokawa Takuya , Matsumoto Yoshihiro , Oya Nozomu , Kitaoka Riki , Yokoi Takato , Narumoto Jin 
Published: February 2025

Abstract

Background
Insomnia is one of the most common disorders in the general population. Although non- pharmacologic interventions are the first-line treatment in many cases[1], pharmacotherapy is an important option in treatment. Because of the risk of various adverse events associated with benzodiazepine receptor agonists (BZRAs)[2], the use of newer hypnotics that target orexin and melatonin (novel hypnotics) has been recommended in recent years[3]. In the present study, we investigated the change in prescriptions of patients prescribed BZRAs after the initiation of the novel hypnotics. This study was approved by the institutional review boards of the participating institutions.

Methods
Changes in prescriptions after the initiation of novel hypnotics were investigated in patients who were prescribed both BZRAs and novel hypnotics who visited the outpatient clinics of all departments of the two general hospitals between May 01, 2021 and April 30, 2022.

Results
We enrolled 534 patients in this study. The mean (SD) age was 58.5 (18.1) and 300 (56%) were female. About half of the prescriptions (297/610) were made by non-psychiatric departments. The most commonly prescribed drugs in the BZRAs were brotizolam (13%, 172/1290) and eszopiclone (11%, 138/1290); the most commonly prescribed novel hypnotic was suvorexant (22%, 282/1290). The mean number of drugs prescribed before and after the addition of novel hypnotics was 1.7 (SD: 0.6), respectively, and 17% (90 patients) had a decrease in the number of medications, while 15% (82 patients) had an increase in the number of medications.

Conclusion
In the present study, no change in the number of medications was observed as a result of the initiation of novel hypnotics in patients prescribed BZRAs. Future studies should investigate which patients succeed/fail in reducing their medications and how this relates to patient background:

References
[1]Sateia MJ et al. Clinical Practice Guideline for the Pharmacologic Treatment of ChronicInsomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med, 2017.
[2]Hirschtritt ME et al. Balancing the Risks and Benefits of Benzodiazepines. JAMA, 2021.
[3]Neubauer DN. Pharmacotherapy for insomnia in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA.(Accessed on December 16, 2023.)