bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACTIVATION OF ANGIOTENSIN-CONVERTING ENZYME 2 PRODUCES AN ANTIDEPRESSANT-LIKE EFFECT IN MICE
Authors: Nakagawasai *Osamu , Takahashi Kohei , Koyama Taisei , Yamagata Ryota , Nemoto Wataru , No Koichi Tan- 
Published: February 2025

Abstract

Background
Angiotensin (Ang) -converting-enzyme (ACE) 2 converts Ang Ⅱ into Ang (1-7), which in turn acts on MAS receptors (ACE2/Ang (1-7)/MAS receptors pathway). This pathway has neuroprotective properties, making it a potential therapeutic target for psychiatric disorders such as depression [1]. Recent studies have reported that diminazene aceturate (DIZE) enhances the catalytic activity of ACE2 by direct binding [2]. Indeed, the administration of DIZE in a diabetic mouse model activated ACE2 and increased Ang (1-7) production [3].

Aims & Objectives
In the present study, to investigate whether ACE2 activation in the brain could be a novel therapeutic target for depression, we examined the effects of DIZE on depressive-like behavior using behavioral, pharmacological, and biochemical assays.

Methods
We measured the duration of immobility of mice in the tail suspension test following their intracerebroventricular administration to determine whether DIZE or Ang (1-7) produce antidepressant- like effects. Next, we measured the levels of ACE2 activation in the cerebral cortex, prefrontal cortex, hippocampus, and amygdala after DIZE injection, and examined which cell types, including neurons, microglia, and astrocytes, express ACE2 in the hippocampus using immunofluorescence.

Results
Administration of DIZE or Ang (1-7) significantly shortened the duration of immobility time in the tail suspension test, while this effect was inhibited by the co-administration of the MAS receptor antagonist A779. DIZE activated ACE2 in the hippocampus. ACE2 was localized to neurons, astrocytes, and microglia in the hippocampus.

Discussion & Conclusion
These results suggest that DIZE may act on ACE2-positive cells in the hippocampus where it increases the activity of ACE2, thereby enhancing signaling of the ACE2/Ang (1- 7)/MAS receptor pathway and resulting in antidepressant-like effects.

References
1.J. Vian, C. Pereira, V. Chavarria, C. Kö hler, B. Stubbs, J. Quevedo, S.W. Kim, AF. Carvalho, M. Berk, BS. Fernandes, The renin-angiotensin system: a possible new target for depression. BMC Med 2017, 15:144
2.L. V. Kulemina, D.A. Ostrov. Prediction of off-target effects on angiotensin-converting enzyme 2. J Biomol Screen 2011, 16:878-885.
3.Y. Zhang, J. Liu, J.Y. Luo, X.Y. Tian, W.S. Cheang, J. Xu, C.W. Lau, L. Wang, W.T. Wong, C.M. Wong, et al. Upregulation of Angiotensin (1-7)-Mediated Signaling Preserves Endothelial Function Through Reducing Oxidative Stress in Diabetes. Antioxid Redox Signal 2015, 23:880-892
EFFECTS OF SODIUM BENZOATE ON BEHAVIORAL AND SYNAPTIC DEFICITS INDUCED BY SUBCHRONIC KETAMINE EXPOSURE IN MICE
Authors: Chan *Ming-Huan , Liu Yi-Hsien , Chen Hwei-Hsien 
Published: February 2025

Abstract

Background
Ketamine, an N-methyl-D-aspartate receptor (NMDAR) blocker, has been used as a dissociative anesthetic and currently become a popular recreational abused substance. Repeated and chronic use of ketamine leads to behavioral disturbances, including social deficits and cognitive impairments in memory. Previous studies indicate that enhancement of NMDAR function reveals the beneficial effects on ketamine-induced abnormal behavioral and neurochemical responses. Sodium benzoate (SB), a D-amino acid oxidase inhibitor, has been reported to improve several neurological disorders, such as depression and schizophrenia, which may be associated with increasing NMDAR function.

Aims & Objectives
This study aimed to investigate the therapeutic effects of SB on ketamine- induced psychotomimetic behaviors and neuronal activity.

Method
The male ICR mice received intraperitoneal injection (i.p.) of either ketamine (20 mg/kg) or vehicle twice per day successively during postnatal days (PN) 32-46. Subsequently, SB (30 &100 mg/kg, i.p.) was given during PN55-69. The novel location/object recognition task, reciprocal social interaction, three-chamber social test, tail suspension test and forced swimming test were monitored. Moreover, a serotonergic hallucinogen was administered to induce head-twitch responses. After animal behavioral tests, the hippocampal synaptic function was determined.

Results
The data showed that the enduring behavioral abnormalities after repeated ketamine exposure, including social deficits, recognition memory impairments, and increased depression- like and hallucinogen-induced head-twitch responses, were ameliorated by SB post-treatment. In addition, SB reversed the reduced hippocampal synaptic activity after repeated ketamine treatment.

Discussion & Conclusion
These results demonstrated that post-treatment with SB could effectively reverse the adverse behavioral manifestations and hippocampal synaptic plasticity after repeated ketamine use, suggesting that SB can be used as a novel adjunct therapy with ketamine for treatment- resistant depression and provide benefits for ketamine use disorders.
THE EFFECT OF LURASIDONE ON PANSS MARDER 5 FACTORS AND INDIVIDUAL ITEMS IN PATIENTS WITH ACUTE SCHIZOPHRENIA: A POST- HOC ANALYSIS OF RANDOMIZED, PLACEBO-CONTROLLED TRIAL (JEWEL STUDY)
Authors: Takai *Kentaro , Miura Itaru , Toya Shunji , Sano Fumiya , Iyo Masaomi 
Published: February 2025

Abstract

Background
Lurasidone is a second-generation antipsychotic approved for the treatment of people with schizophrenia in Japan, the United States, European Union, and many other countries worldwide. It possesses high affinity for D2, 5-HT7, 5-HT2A and 5-HT1A receptors and no affinity for H1 and M1 receptors.

Aims & Objectives
The objective of this post-hoc analysis was to evaluate the effect of lurasidone 40mg/day (LUR) on PANSS Marder 5 factors and individual items in people with acute schizophrenia.

Method
A post-hoc analysis was conducted using the data from patients in a phase 3 study of lurasidone (a 6-week, randomized, placebo-controlled trial; JEWEL study). The study was approved by ethical committees in each country, complied with ICH-GCP guidelines, and written informed consent from all subjects was obtained. Change from baseline in Positive and Negative Syndrome Scale (PANSS) Marder 5 factor and 30 individual item scores between LUR and placebo (PBO) at each assessment point were compared using a mixed-effects model for repeated measures.

Results
Mean change from baseline of all Marder 5 factor scores in LUR at week 6 were statistically greater (p&lt;0.05) than one in PBO (positive symptoms, negative symptoms, disorganized thought, hostility/excitement and anxiety/depression [LS mean] were -6.6, -3.8, -3.7, -2.0 and -3.4 in LUR and -4.3, -2.9, -2.5, -1.2 and -2.5 in PBO, respectively). Changes in 4 factors other than negative symptoms in LUR were statistically greater than one in PBO from week 2. Among PANSS 30 individual items that consist Marder factors, P1, P2, P3, P6, P7, N5, G1, G2, G4, G9, G11, G14, G15 and G16 showed statistically greater change from baseline at week 6 in LUR compared to PBO.

Discussion & Conclusion
In this post-hoc analysis, lurasidone showed the effect on various psychotic symptoms in JEWEL study, suggesting lurasidone is considered to be an effective option for acute schizophrenia.
ANTIPSYCHOTICS AND MORTALITY IN PATIENTS AND ELDERLY PATIENTS WITH SCHIZOPHRENIA: A NATIONWIDE COHORT STUDY IN TAIWAN
Authors: Lee *Wei-Chen , Yeh Ling-Ling , Pan Yi-Ju 
Published: February 2025

Abstract

Background
Patients with schizophrenia had higher mortality rates, experiencing a 15-year reduction in life expectancy in Taiwan compared to the general population [1]. The causes of excess mortality were multifaceted, and the role of antipsychotic medications in mortality remained inconclusive. Additionally, as the population continued to age gradually, elderly schizophrenia was a population that required much attention.

Aims & Objectives
We aimed to investigate excess mortality in schizophrenia patients based on cumulative antipsychotic exposure and explore medication dosage associations with mortality in the adult and elderly schizophrenia population.

Method
This population-based cohort study examined patients with schizophrenia using Taiwan’ s national health insurance database. The cohort included individuals aged 15 years or older diagnosed with schizophrenia in 2010, followed for five years (2010–2014). A subgroup of elderly patients was also studied. Mortality in schizophrenia patients was compared to an age- and gender- matched control sample. Cox regression models assessed overall and cardiovascular mortality based on different antipsychotic exposure levels, using two models: one adjusted solely for age and sex, and the other adjusted for covariates including demographic, socioeconomic data, and comorbid physical illnesses.

Results
We examined 102,964 patients with schizophrenia, including 6,433 elderly patients. In comparison to age- and gender-matched controls, schizophrenia patients with no antipsychotic exposure exhibited the highest overall mortality risk and cardiovascular mortality, followed by high exposure, low exposure and moderate exposure groups. A similar pattern was observed in elderly schizophrenia patients, but high antipsychotic exposure associated with the highest risk in both overall and cardiovascular mortality in elderly patients.

Discussion & Conclusions
Use of antipsychotics is beneficial to patients with schizophrenia, with the most recommended antipsychotic exposure range from low to moderate exposure. Overall, antipsychotic exposure showed a U-shaped pattern in both overall and cardiovascular mortality for patients with schizophrenia and elderly schizophrenia patients, respectively. In elderly patients, high antipsychotic exposure was associated with the highest mortality risk, contrasting with all patients with schizophrenia.

References
[1]Pan, Y.-J., Yeh, L.-L., Chan, H.-Y. and Chang, C.-K. (2020). Excess mortality and shortened life expectancy in people with major mental illnesses in Taiwan. Epidemiology and psychiatric sciences, 29, p.e156.
THE NEURONAL CIRCUITS IMPLICATED IN THE PHENCYCLIDINE-INDUCED BEHAVIORAL IMPAIRMENTS AND THERAPEUTIC AND SIDE EFFECTS OF ARIPIPRAZOLE
Authors: Ando *Fumika , Mouri Akihiro , Kunisawa Kazuo , Yamagishi Shuhei , Komaki Yuji , Takano Kazuki , Nabeshima Toshitaka 
Published: February 2025

Abstract

Background
Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms and cognitive impairments. Second-and third-generation antipsychotics alleviate not only positive symptoms but also negative symptoms and cognitive impairments, with a lower liability for extrapyramidal symptoms (EPS).Accumulating evidences suggest that dopaminergic mesocorticolimbic and nigrostriatal pathways implicated in the pathophysiology of schizophrenia and the therapeutic and side effects of antipsychotics. However, the detailed mechanism remains unclear.

Aims & Objectives
To explore them, we investigated the neuronal circuits implicated in the therapeutic and side effects of aripiprazole, a dopamine D2 receptor partial agonist, in the animal model of schizophrenia by using connectome analysis.

Method
A mouse model of schizophrenia was prepared by phencyclidine (PCP), s.c. injection to ddY mice for 14 consecutive days.

Result
Repeated PCP induced the sensitization of PCP-induced hyperactivity, social deficit and impairment of object recognition memory which associated with increase of dopamine turnover in the nucleus accumbens, but decreases of it in the prefrontal cortex. Aripiprazole (0.3mg/kg) improved these PCP- induced behavioral changes. However, aripiprazole (3.0mg/kg) induced catalepsy such as EPS-like behavior. Connectome analysis using MRI revealed that repeated PCP administration decreased functional connectivity, but aripiprazole (0.3mg/kg) attenuated it. However,aripiprazole (3.0mg/kg) further increased functional connectivity.

Discussion & Conclusion
These results suggest that aripiprazole (0.3mg/kg) improves PCP-induced behavioral changes and decreased functional connectivity by attenuating dopaminergic disfunction, but high-dose aripiprazole (3.0mg/kg) induces catalepsy associated with increased functional connectivity induced by excessive dopamine D2 receptor antagonism.
NEUROFILAMENT LIGHT AND GLIAL FIBRILLARY ACIDIC PROTEIN AS A DIAGNOSTIC AND PROGNOSTIC BIOMARKER FOR MOOD DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kang *Matthew Jee Yun , Grewal Jasleen , Malpas Charles , Chiu Wei-Hsuan Michelle , Mitchell Phil , Hopwood Mal , Eratne Dr Dhamidhu , Velakoulis Dennis 
Published: February 2025

Abstract

Background
Blood-based biomarkers of neuronal injury (NfL) and neuroinflammation (GFAP) are being increasingly used for diagnosis and prognosis in neurodegenerative conditions including multiple sclerosis. However, current literature is mixed as to whether these biomarkers are mildly elevated in mood disorders, heralding an opportunity to identify a potential indicator of mood disorders including treatment response. Better understanding the behaviour of these biomarkers in people with mood disorders will help elucidate the neurobiological underpinnings, opening up avenues for psychopharmacology targets.

Aims & Objectives
The aim of this systematic review is to identify the association between neuronal and glial biomarkers in patients with mood and anxiety disorders compared to healthy controls.

Methods
A protocol for a systematic review has been submitted to PROSPERO, with the initial literature search identify 1994 papers. A meta-analysis will be performed comparing biomarker levels in mood disorders, separated into major depression and bipolar disorder, as well as robust assesmsent of bias risk in the studies. If appropriate, we will perform meta-regression analyses of comparing severity of mood disorders with biomarker levels, as well as performing subgroup analyses of those with later- onset illness.

Results
We plan to complete the review and present the findings at CINP 2024. Furthermore, we plan to perform a mega-analysis using the data pooled from our search.

Discussion
Our findings will be important for the translation of these biomarkers to clinical practice, as it will either validate the use to detect neurodegenerative disorders in people presenting with mood symptoms, or potentially identify prognostic and diagnostic blood-based biomarkers for mood disorder.
DIFFERENCES IN FUNCTIONAL CONNECTIVITY BETWEEN PATIENTS WITH DEPRESSION WITH AND WITHOUT NONSUICIDAL SELF-INJURY
Authors: Lee Hye-Jin , Park *Young-Min , Shim Miseon 
Published: February 2025

Abstract

Background
Nonsuicidal self-injury (NSSI), which involves deliberate harm to body tissues without suicidal intent, represents an escalating clinical concern.

Aims & Objectives
We used electroencephalography (EEG) to investigate the differences in functional connectivity (FC) patterns in patients with depression with and without a history of NSSI.

Method
Seventy-seven patients with mood disorders experiencing major depressive episodes were categorized into NSSI (Group A; n = 31) and non-NSSI (Group B; n = 46) groups on the basis of their NSSI history. EEG data were collected and FC was analyzed using coherence (Coh), imaginary coherence (iCoh), and phase-locking value (PLV) metrics. Network indices based on graph theory were calculated. Demographic and clinical characteristics and scale scores were compared between groups A and B.

Results
While the two groups showed no significant differences in demographic characteristics such as age and diagnosis, the Beck Depression Inventory and Suicidal Ideation Questionnaire (SIQ) scores were higher in Group A. Binary logistic regression analyses revealed associations of NSSI with sex and the SIQ score. We examined the connectivity of 1,326 pairs of signals across six frequency bands, yielding 7,956 signal pairs. The two groups showed no significant differences in the Coh, iCoh, corrected PLV, or network indices but showed significant differences in all the frequency bands when an uncorrected t- test was used.

Conclusions
This study confirmed the differences in FC between patients with depression with and without NSSI. These insights will further clarify the neurobiological underpinnings of NSSI and may guide future investigations and interventions.
RELEVANCE BETWEEN AGE OF ONSET AND HOSPITALIZATION CHARACTERISTICS OF MAJOR DEPRESSIVE DISORDERS: A 16 YEARS RETROSPECTIVE COHORT STUDY
Authors: Zhang *Kai , Yao Yitan , Yang Qiongyao , Chen Chuanchuan , Wang Yue , Wang Wenhui , Zhang Miaomiao , Zhong Yongjie , Yuan Xiaoping 
Published: February 2025

Abstract

Background
Age of onset influences the progression of many diseases and even serves as a potential driver. But in Major Depressive Disorder, there are no uniform findings on the effect of age of onset on the course of the disease.

Objectives
We thus retrospectively investigated a large-scale cohort to explore the effect of age of onset on the course of Major Depressive Disorders.

Method
In this study, a total of 38,671 inpatients were surveyed over 16 years, and 6,773 inpatients were eventually included in the statistical analysis after applying rigorous data criteria. We used logistic regression models to calculate the odds ratio for the risk of relapse.

Results
In the subset of 4884 participants with first hospitalization, the first episode of depressive disorder was concentrated in middle age (39.5%). The differences in the length of stay in the different age of onset groups were statistically significant (F=56.852, df1=3, df2=4880, P&lt;0.001, ω2=0.033), and the Bonferroni post hoc test suggested a longer length of stay in the adolescent onset group. Similarly, this difference was also observed in the subset of 1229 participants with relapse hospitalization(F=5.985, df1=3, df2=1225, P&lt;0.001, ω2=0.012). The proportion of patients in the adolescent-onset group with 2 or more relapse hospitalizations within 1 year was found to be higher than that without relapse (6.7%Vs 2.7%, X2=12.685, df=6, P &lt;0.001). Logistic regression suggests that patients with adolescent onset are at higher risk for 2 or more relapses within one year (B=0.881, OR=2.41, 95%CI 1.37-4.23, P=0.002).

Conclusions
This is the first large sample size study to examine age at onset and risk of relapse at the individual level in a Chinese population. Our study found that adolescent onset is more likely to lead to chronicity of MDD. These findings will contribute to more precise disease typing in MDD, as well as customized individualized prevention and treatment programs.
EVALUATION OF BEHAVIORAL SELECTION PROCESSES IN CONFLICT SCENARIOS USING A NEWLY DEVELOPED MOUSE BEHAVIORAL PARADIGM
Authors: Honshuku *Yuki , Hitora-Imamura Natsuko , Miyagami Yurika , Nomura Hiroshi , Katsuki Hiroshi , Minami Masabumi 
Published: February 2025

Abstract

Background
Selecting an appropriate behavior is critical for survival in conflict situations during which animals face both appetitive and aversive stimuli. Animals in conflict situations exhibit several processes. First, they stay still in a safe place (suspension); once they decide to take action, they assess risks at a place where danger may occur (risk assessment) and finally reach the reward. However, most studies have not addressed these conflict processes.

Aims & Objectives
We developed a new experimental paradigm– the three-compartment conflict task– to quantitatively evaluate conflict processes and examine the pharmacological validity of the task.

Method
The experimental apparatus for the three- compartment conflict task consisted of start, flat, and grid compartments. Mice were required to explore the grid compartment where they might receive electric footshocks while trying to obtain sucrose. We injected them with diazepam (1.0 mg/kg) intraperitoneally to evaluate its previously reported anti-conflict effect.

Results
We found that applying foot shocks increased sucrose acquisition latency, time in the start compartment, and the number of retreats in the subsequent trials, reflecting an elevated conflict level throughout the trials, in suspension, and in risk assessment, respectively. Strong footshock changed the location of retreats from near to far from the danger zone, reflecting fear generalization. Treatment with diazepam decreased these parameters.

Discussion & Conclusion
Our new paradigm is a valuable tool for quantitatively evaluating conflict processes and investigating the cognitive and neural basis of such behavior.
KEY FACTORS ASSOCIATED WITH TREATMENT-RESISTANT DEPRESSION- RELATED COGNITIVE DECLINE IN DIFFERENT AGE
Authors: Lee *Chi-Wei , Yang Tzu-Jung , Chu Ming-Chia , Chi Hsiang , Li Cheng-Ta , Lin Hui-Ching 
Published: February 2025

Abstract

Background
Cognitive dysfunction is strongly associate with late-life depression. Previous study further indicated that treatment-resistant depression (TRD) patients, which refers poor responses to adequate antidepressant treatment, have prominent cognitive impairment. Moreover, the depression patients with cognitive impairment could be a risk factor for dementia. Recent study revealed that increase of eIF4E phosphorylation have found highly associate with cognitive dysfunction and depressive symptom. The antidepressant effect of low-dose ketamine, which effective in treating TRD, is involved in regulate eIF4E. Previous study further indicated dramatic increase of eIF4E phosphorylation was observed in post-mortem of Alzheimer's disease patients. As mention above, eIF4E may be considered a potential target crossing the cognitive dysfunction and depressive symptom underlying aging.

Aims & Objectives
We hypothesized that eIF4E phosphorylation may involve in cognitive dysfunction and depression, especially TRD, following aging. In present study, we performed the TRD mice model which induced by traumatic stress in young- and mid-age mice.

Method
We applied the traumatic stress to induce the TRD mice model. The behavior tests were examined the depressive-like behaviors. The synaptic plasticity such as long-term potentiation (LTP) was examine by electrical physiology. The phosphorylation of eIF4E was examine by western blotting.

Results
The results indicated that depressive-like behavior was found after traumatic stress in both young- and mid-age mice. While, the cognitive impairment induced by traumatic stress was worse in mid-age mice. Moreover, the increased eIF4E phosphorylation was greater after traumatic stress in mid-aged mice. The depressive-like behavior was improved by eIF4E phosphorylation inhibition. Furthermore, the cognitive impairment only improved by inhibition of eIF4E phosphorylation.

Discussion & Conclusion
Present study demonstrated the relationship between cognitive dysfunction and depression, especially TRD population, following aging. Our finding further provided the evidences that eIF4E may a key factor which highly associate with cognitive dysfunction and depression following aging. To date, effective therapeutic strategy for cognitive dysfunction with TRD remain urgent. EIF4E may be considered a potential target for this issue.