bluuebunny/crossref_metadata_2025 huggingface dataset:
UTILIZING AI MODELS TO IDENTIFY AND PREDICT MOOD TRANSITION PATTERNS IN PATIENTS WITH BIPOLAR DISORDER
Authors: Feng *Xiaoyang , Ma Yantao , Guo Liangkun , Zhang Yuyanan , Sun Yaoyao , Lu Zhe , Liao Yundan , Kang Zhewei , Yu Xin , Yue Weihua
Published: February 2025

Bipolar disorder is characterized by recurrent episodes of depression and mania, making diagnosis and treatment challenging, often leading to poor prognosis. Predicting future episodes based on the assessment of current and past emotional phases in patients can offer valuable insights for clinicians, aiding in the prevention of misdiagnosis and relapse, and in intervention strategies. This study included 812 patients with bipolar disorder from 9 centers, who were assessed online or offline using BDCC, YMRS, and HAMD tools. We employed four AI methodologies to learn from the assessment results and time series, ultimately predicting future emotional phases of the patients. By learning from current assessment results to predict the next emotional phase, the AUCs of the four models were 0.81, 0.70, 0.84, and 0.81, respectively. External validation on 30-day and 90-day emotional phase follow-ups of patients showed prediction accuracies of 0.9, 0.65, 0.86, and 0.62 for each model. While predictive efficacy decreased over time, the average AUC remained above 0.75 at 180 days. Our findings suggest that utilizing big data and AI methods can effectively learn the characteristics of emotional phase transitions in bipolar patients, achieving high accuracy. This model holds significant value for clinical diagnosis and medication guidance for clinicians
SEX DIFFERENCES IN NEURAL PROJECTIONS OF FEAR MEMORY PROCESSING IN MICE AND HUMANS
Authors: Andero *Raul
Published: February 2025

Background

The Tac2 pathway is a pharmacological opportunity for brain disorders since Tac2 antagonists are safe and well tolerated in humans and modulate memory in rodents.

Aims & Objectives

It remains unexplored whether the connectivity between two brain areas is necessary for one sex, but not in the other one, for the formation of the same memory.

Method

In mice we used fear procedures, chemogenetics, clozapine N-oxide delivered intracerebrally and systemically, immunohistochemistry, electrophysiology and in vivo calcium imaging in freely moving mice. In humans we used fear procedures, neuroimaging and genetic analyses of post-mortem brain tissue.

Results

Here, the chemogenetic silencing of CeM-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreases fear memory consolidation in male mice, but not females. Optogenetic excitation of CeM-Tac2 shows increased inhibitory post-synaptic currents in the BNSTpl of males compared to females. In vivo calcium imaging analysis reveals a sex-dimorphic fear memory engram in the BNSTpl. In humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreases the CeM-BNST connectivity in a fear task, impairs fear memory consolidation and increases the expression of the TAC3R mRNA in AA-carrier men but not in women.

Discussion & Conclusion

These sex differences in necessary neuronal projections of fear memory formation may be relevant for mental disorders with memory alterations. Also, these data highlight the role of Tac2 antagonists in treating and preventing fear-based disorders.
A MACHINE LEARNING APPROACH TO PREDICT THE THERAPEUTIC EFFICACY OF MOBILE NEUROFEEDBACK IN CHILDREN WITH ADHD
Authors: Kim *Junwon , Yang Seungheon , Han Sooin
Published: February 2025

Background

Attention-Deficit/Hyperactivity Disorder (ADHD) is a type of neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity, associated with adverse long-term functional outcomes. Neurofeedback training as an add-on to medication therapy has been proposed.

Aims & Objectives

This study aimed to evaluate the effectiveness of machine learning (ML) models in predicting the therapeutic response to mobile neurofeedback (MNF) in children diagnosed with ADHD. Method: A total of 41 children with ADHD were allocated to one of two groups: ADHD MNF-medication (n=28) and ADHD MNF alone (n=13). Participants already receiving medication for ADHD maintained their medication dosages throughout the MNF treatment period. The MNF program was administered three days a week, twice daily, for 10-20 minutes over a span of 12 weeks. The assessment of the MNF's effectiveness was based on changes in the Clinical Global Impression-Severity scale (CGI-S). We quantified absolute and relative power across 19 channels and analyzed quantitative electroencephalography (qEEG) data within the following frequency ranges: delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–25 Hz), high beta (25–30 Hz), and gamma (30–80 Hz). We employed the XGBoost algorithm to determine the classification potential based on quantitative EEG characteristics and achieved optimal classification performance through hyperparameter optimization, utilizing Python- based XGBoost software.

Results

The highest classification performance obtained through hyperparameter optimization yielded an accuracy rate of 99.7%. To assess the contribution of individual features to the classification, we quantified the impact on classification performance for each group using SHAP (SHapley Additive exPlanations) values and identified the top 10 contributing features. Notably, in the classification based on EEG data obtained with eyes closed, the following features exhibited high importance: F7 (Delta), Fp1 (Delta), F8 (Low Beta), F8 (Beta), F7 (Relative Delta), F4 (Middle Beta), F4 (Beta), Fp1 (Gamma), F7 (Gamma), and O2 (Middle Beta / Theta).

Discussion & Conclusion

Our machine learning analysis demonstrated a high level of accuracy in predicting the therapeutic response to mobile neurofeedback. Notably, delta and beta waves in the frontal lobe were identified as having the highest impact on classification performance.
SOURCES OF INFORMATION ABOUT COVID-19 VACCINES FOR CHILDREN AND ITS ASSOCIATIONS WITH PARENTAL MOTIVATION TO HAVE THEIR CHILDREN VACCINATED IN TAIWAN
Authors: Liu *Tai-Ling , Yen Cheng-Fang
Published: February 2025

Vaccines have been developed for children to prevent them from being contracted by COVID-19; however, parental hesitancy to have their children vaccinated against COVID-19 is prevalent. Sources of information about COVID-19 vaccines have been found to influence individuals’ motivation to vaccinate. The aims of this study were to examine parents’ sources of information about COVID-19 vaccines for children and trust of information sources, their demographically related factors, and associations of information sources with parental motivation to have their children vaccinated against COVID-19. In total, 550 parents of children (123 males and 427 females) were completed the research questionnaires. Sources from which parents received the information about child COVID-19 vaccines and parents’ trust of the information were surveyed. Parental motivation to have their children vaccinated was measured using the Parent Version of the Motors of COVID-19 Vaccination Acceptance Scale. The associations of sources of information and their trust with parental motivation to have their children vaccinated and associations of parents’ demographics with the sources of information and their trust were examined using multivariate linear regression analysis. Traditional mass media and medical staff in health care settings were the most common sources from which parents received information for child COVID-19 vaccines. Medical staff in health care settings were rated by the parents as the most trustworthy source of information. Receiving information from acquainted people in social media and medical staff in health care settings were significantly associated with parental motivation to have their children vaccinated against COVID-19. Trust in the information from medical staff in health care settings and coworkers were significantly associated with parental motivation to have their children vaccinated against COVID-19. Compared with males, females were more likely to receive information from medical staff in health care settings and acquainted people in social media. Parents with a higher education level were more likely to receive information from medical staff in health care settings. Compared with males, females had greater trust in the information received from coworkers. Health professional should take the sources of information and related factors into consideration when develop intervention programs for enhancing parental motivation to have their children vaccinated against COVID-19.
PREDICTORS OF PSYCHIATRIC HOSPITALIZATION AMONG OUTPATIENTS WITH BIPOLAR DISORDER IN THE REAL-WORLD CLINICAL SETTING
Authors: Tokumitsu *Keita , Yasui-Furukori Norio , Adachi Naoto , Kubota Yukihisa , Watanabe Yoichiro , Miki Kazuhira , Azekawa Takaharu , Edagawa Koji , Katsumoto Eiichi , Hongo Seiji , Goto Eiichiro , Ueda Hitoshi , Kato Masaki , Nakagawa Atsuo , Kikuchi Toshiaki , Tsuboi Takashi , Watanabe Koichiro , Shimoda Kazutaka , Yoshimura Reiji
Published: February 2025

Background

Bipolar disorder is a psychiatric disorder that causes recurrent manic and depressive episodes, leading to decreased levels of social functioning and suicide. Patients who require hospitalization due to exacerbation of bipolar disorder have been reported to subsequently have poor psychosocial functioning, and so there is a need to prevent hospitalization. On the other hand, there is a lack of evidence regarding predictors of hospitalization in real-world clinical practice.

Aims & Objectives

We investigated the yearly rate of hospitalization and predictive factors for hospitalization among outpatients with bipolar disorder.

Method

The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was an observational study conducted to provide evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked, as part of a retrospective medical record survey, to fill out a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. Our study extracted baseline patient characteristics from records dated between September and October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. The incidence and predictors of hospitalization among patients with bipolar disorder over a 1-year period extending from that baseline to September-October 2017 were examined.

Results

In total, 2,389 participants were included in our study, 3.06% of whom experienced psychiatric hospitalization over the course of 1 year from baseline. Binomial logistic regression analysis revealed that the presence of psychiatric hospitalization was correlated with bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and manic state.

Discussion & Conclusion

Our study revealed that 3.06% of outpatients with bipolar disorder were subjected to psychiatric hospitalization during a 1-year period that extended to September-October 2017. Our study suggested that bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and baseline mood state could be predictors of psychiatric hospitalization. These results may be useful for clinicians seeking to prevent psychiatric hospitalization for bipolar disorder.

References

Tokumitsu K, et al. Predictors of psychiatric hospitalization among outpatients with bipolar disorder in the real-world clinical setting. Front Psychiatry. 2023 Mar 16;14:1078045.
RELATIONSHIP BETWEEN CHILDHOOD TRAUMA AND MITOCHONDRIAL DYSFUNCTION IN BIPOLAR DISORDER AND HEALTHY INDIVIDUALS
Authors: Wu *Cheng Ying
Published: February 2025

Background

Mitochondria, essential for energy production, can inadvertently produce reactive oxygen species. Measuring mitochondrial DNA (mtDNA) copy number provides a window into mitochondrial function. Changes in mtDNA copy number can occur due to genetic mutations, environmental factors, and inflammation, influencing various health outcomes. Dysfunctional mitochondria are linked to increased oxidative stress and inflammation, contributing to diverse diseases. In BD, mitochondrial dysfunction is intricately tied to the disease's pathological manifestations, affecting energy metabolism and intracellular calcium signaling. Alterations in mtDNA copy number have been observed in manic and depressed BD patients. Additionally, childhood trauma has been identified as a major risk factor for BD and has been associated with increased susceptibility to and severity of the disorder, although the specific role of each trauma subtype (emotional, physical, or sexual abuse) remains a topic of debate. Previous research has established that both BD and childhood trauma are independently associated with mitochondrial abnormalities. However, the potential association between childhood trauma, mitochondrial dysfunction, and BD has not been thoroughly investigated.

Aims & Objectives

Prior research has shown an increased incidence of childhood trauma in individuals diagnosed with bipolar disorder (BD). It has also been independently established that both childhood trauma and mitochondrial dysfunction have connections with BD. Consequently, the aim of this study is to explore whether there might be a link between mitochondrial dysfunction and childhood trauma in people suffering from BD.

Method

The study involved 60 participants diagnosed with BD and 26 individuals serving as healthy controls. To gather data, the Childhood Trauma Questionnaire (CTQ) was utilized, and blood samples were collected for the purpose of determining mitochondrial DNA copy number (MCN) from leukocytes. An examination was then conducted to identify any correlation between CTQ scores and MCN.

Results

Compared to the healthy controls, the BD group exhibited slightly lower MCN, which did not reach significance. However, the CTQ sum scores were significantly higher in the BD group. After controlling age, gender, and BMI, negative correlations were found between CTQ scores, particularly emotional neglect (r = -0.431, p = 0.04), emotional abuse (r = -0.425, p = 0.043), and total scores (r = - 0.513; p = 0.012), and MCN within the healthy control group. Nevertheless, no substantial correlation was observed between CTQ and MCN in the participants with BD.

Discussion & Conclusion

Childhood traumata have different effects on BD compared to healthy individuals. Therefore, a comprehensive investigation of the complex relationship between childhood trauma, BD, and medication effects is crucial to better understand how trauma impacts individuals living with this psychiatric condition.
THE ASSOCIATION OF KLOTHO/FIBROBLAST GROWTH FACTOR 23 WITH COGNITIVE FEATURES IN ELDERLY PATIENTS WITH BIPOLAR DISORDER
Authors: Chen *Wen Yin , Chiu Chih Chiang , Kuo Po-Hsiu , Huang Cho-Yin , Kuo Chian-Jue , Chen Po-Yu , Huang Ming-Chyi
Published: February 2025

Background

Cognitive aging is a known phenomenon in individuals with bipolar disorder (BD), but the underlying biological mechanisms responsible for this cognitive decline remain poorly understood. One potential avenue of investigation is the dysfunction of the Klotho/Fibroblast Growth Factor 23 (FGF23) system, which has been linked to reduced lifespan and age-related diseases, including dementia. However, there is limited research on the relationship between Klotho/FGF23 levels and aging in BD patients, as well as their association with cognitive decline in elderly individuals with BD.

Aims

The aim of this study was to explore the levels of Klotho and FGF23 in elderly BD patients and their relationship with the aging profile and cognitive domains.

Methods

The study included 85 euthymic, elderly participants aged 50 or older, who also had adequate kidney function and were diagnosed with BD-I. Cognitive function was assessed using the Brief Assessment of Cognition in Affective Disorders. The study examined the correlations between Klotho and FGF23 levels and other aging-related assessments. General linear models were then used to identify associations between Klotho and FGF23 levels and various cognitive domains.

Results

The average age of the participants was 59.64 years. The mean Klotho and FGF23 levels were 0.71 ng/ml and 15.02 ng/ml, respectively. Positive correlations were found between Klotho and FGF23 (r= 0.352, p = 0.002) and between creatine levels and Klotho/FGF23 (r = 0.328, p = 0.016 for Klotho and r= 0.302, p = 0.028 for FGF23). Higher levels of FGF23 were significantly associated with lower composite cognitive scores (β= -0.003, p = 0.005), particularly in verbal memory (β= -0.002, p = 0.013), motor speed (β= -0.002, p = 0.027), and processing speed (β= -0.002, p = 0.029). No significant association was observed between Klotho levels and cognitive domains.

Conclusion

In elderly individuals with BD, this study found that higher FGF23 levels were associated with negative effects on cognitive domains, particularly in verbal memory, motor speed, and processing speed. However, no significant association was found between Klotho levels and cognitive performance. Future research is needed to further define the dysfunction of the Klotho/FGF23 axis and conduct longitudinal studies that incorporate validated aging clinical markers to better understand the underlying mechanisms of cognitive aging in BD.
BRAIN NEURONAL INTEGRITY IN COVID-19 PATIENTS IN TAIWAN
Authors: Liu *Tung-Hsia , Wang Chih-Hui , Huang Shiu-Feng , Tsou Hsiao-Hui , Yu Guann-Yi , Chen Andrew C H , Chen Wei J , Liu Yu-Li
Published: February 2025

Background

COVID-19 has caused a global pandemic characterized by severe pneumonia. Brain structure abnormality has been confirmed in COVID-19 patients in the UK biobank [1]. However, it is not clear whether this abnormality is reversible nor if the abnormality could be detected in the early stage of the disease.

Aims & Objectives

In this study, the pathological effect of COVID-19 on the brain integrity was monitored through the utilization of a brain injury bioindicator, neurofilament light chain (NFL) [2]. It can be released from the brain into the peripheral blood when the brain neuronal axon is injured [3]. The study aimed to assess the correlation between the discharge diagnoses and NFL levels in COVID-infected patients.

Method

Plasma samples from the National Health Research Institutes (NHRI) Biobank of 400 COVID-19 patients recruited from 24 hospitals across Taiwan were used for NFL analyses by immunoassay.

Results

Among the successfully analyzed 394 patients, 10 patients (2.5%) showed an NFL level above 200 pg/ml. The mean NFL levels were significantly higher in patients older than 50 years (P <0.0001). Male patients had a higher NFL level than females (P = 0.008). The increase in plasma levels of NFL was the highest in the first 1-7 days after the COVID-19 diagnosis was confirmed, then gradually decreased within a month. Significant higher NFL levels were observed in patients with hospitalization, respiratory or ICU treatment, and oxygen therapy (P <0.0001). Moreover, higher NFL levels were also correlated with discharge diagnoses of cardiovascular, lung, kidney, and other chronic diseases (P ≦ 0.008).

Discussion & Conclusion

COVID-19 infection may cause brain neuronal injury especially in male patients older than 50 years. In addition, the plasma NFL level was associated with a number of clinical features. The results demonstrated that NFL could be an indicator for assessing the brain neuronal integrity following COVID- 19 infection.

References

1.Douaud, G., et al., SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, 2022. 604(7907): p. 697-707.

2.Lee, M.K. and D.W. Cleveland, Neuronal intermediate filaments.Annual review of neuroscience, 1996. 19(1): p. 187-217.

3.Khalil, M., et al., Neurofilaments as biomarkers in neurological disorders. Nature Reviews Neurology, 2018. 14(10): p. 577-589.
CHANGES IN MENTAL HEALTH AND LIFESTYLE HABITS OF KOREAN ADOLESCENTS DUE TO COVID-19 PANDEMIC
Authors: Lee *Jongha , Chi Suhyuk , Chae Boram , Kim Seo Jung
Published: February 2025

Background

The coronavirus disease 2019 (COVID-19) pandemic has had a wide-ranging impact on the lives and mental health of adolescents.

Aims & Objectives

We need to assess changes in adolescents' mental health and lifestyle habits.

Method

We conducted a secondary analysis using from a national cross-sectional cohort (Korean Youth Risk Behavior Web-Based Survey, KYRBS) collected before the COVID-19 outbreak (2018, 2019), during the pandemic (2020, 2021), and after the pandemic (2022).

Results

The degree of recovery from fatigue due to sleep showed improvement after the outbreak of the pandemic, but showed a pattern of worsening after the pandemic ended. The physical activity time has actually decreased due to the pandemic. Even though physical activity time has increased since the end of the pandemic, sleep quality appears to have decreased. The frequency of feeling sad and desperate decreased slightly during the pandemic, but increased after the pandemic compared to before the pandemic. Suicide-related indicators of suicidal thoughts, plans, and attempts also showed the same pattern, decreasing during the pandemic and then increasing again. the rate of male students experiencing sadness increased significantly after the end of the pandemic.

Discussion & Conclusion

Mental health-related problems among adolescents in Korea appear to be equal to or more severe than before the outbreak of the pandemic. We can see that the end of the COVID-19 pandemic cannot be equated with the end of the threat to youth mental health.
THE ASSOCIATION BETWEEN DEPRESSION DURATION, THE SEVERITY OF PSYCHOSOCIAL STRESS, AND ANTIDEPRESSANT EFFICACY OF PREFRONTAL STIMULATION IN PATIENTS WITH TREATMENT-RESISTANT DEPRESSION
Authors: Cheng *Chih-Ming , Li Cheng-Ta , Bai Ya-Mei
Published: February 2025

Background

While psychosocial stress and episode duration do influence the treatment of depression, their effects on the antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS) are not yet well evaluated.

Methods

Data from a randomized, double-blind, sham-controlled prolonged intermittent theta-burst stimulation (piTBS) trial on the treatment of depression were utilized in this exploratory study. For a two-week intervention, 105 patients with treatment-resistant depression were randomly assigned to receive piTBS, 10Hz-rTMS, or sham monotherapy. The sham group was used the sham coil that could mimic the auditory and somatosensory effects of active coil stimulation without actual stimulation of the brain. 17-item Hamilton Depression Rating scale (HDRS-17) were obtained at baseline, week-1 and week-2. The baseline Holmes– Rahe Life-Stress Inventory was utilized to categorize patients into conditions of low and high severity of psychosocial stress. The cut-off value that separates between acute and chronic current episode duration was established at one year. The primary outcome was the %HDRS-17 changes after treatment.

Results

In contrast to the sham intervention, piTBS exhibited a noteworthy decrease in HDRS-17 for both low- stress acute and chronic depression (-47% vs. 12%, p<0.001; -32% vs. −8%, p<0.05, respectively). However, for high-stress acute and chronic depression, there was no statistically significant difference of the efficacy between piTBS and sham group (-42% vs. −22%; -33% vs.−22%, respectively).In addition, although chronic depression exhibited a lower rate of remission compared to acute depression among patients who received piTBS, both of their HDRS-17 score consistently declined over the course of two weeks. Placebo effect was positively correlated to stress severity in sham stimulation, but did not contribute significantly to the antidepressant efficacy in active stimulation.

Conclusion

This is the first study to evaluate the importance of depression chronicity and psychosocial stress severity, and the antidepressant effects of rTMS. By utilizing these two readily accessible clinical predictors, rTMS treatment can be more tailored individually. In addition, our findings suggested that early consideration about providing prefrontal stimulation in depressed patients who do not respond to antidepressants.
EFFECTS OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION OF THE LEFT DORSOLATERAL PREFRONTAL CORTEX ON SYMPTOM DOMAINS IN MOOD DISORDERS
Authors: Chen *Po See , Yek Chin Wei , Lu Tsung-Hua , Wang Tzu-Yun , Chang Wei Hung , Tseng Huai-Hsuan
Published: February 2025

Objectives

The primary objective of this study is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on symptom domains in mood disorders. Specifically, we endeavor to characterize the alterations of mood symptoms and clarify if improvement in mood symptoms is concurrently associated with enhancements in social cognition abilities in individual cases.

Methods

Individuals diagnosed with unipolar or bipolar depression participated in a series of 12 sessions of 10 Hz rTMS directed at the left DLPFC, with an 8-week follow-up. Evaluation of mood symptoms and social cognition abilities was conducted utilizing the 24-item Hamilton Depression Rating Scale (HDRS- 24) and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

Results

The study was completed by forty-four depressed patients (20 bipolar and 24 unipolar) with an average age of 45.43±2.505. The mean baseline HDRS-24 total score was observed at 26.39±0.744, which significantly reduced to 9.64±1.126 posttreatment (p <0.001), and further declined to 9.25±1.101 at the 4-week follow-up (p <0.001), and 9.55±1.446 at the 8-week follow-up (p <0.001). The significant decrease in the total score of HDRS was attributed to the decline in the subscores of individual items, except for items 17, 19, 20, and 21. Comparing the item-level changes between bipolar and unipolar depression groups, significant differences in changes emerge in questions 2, 3, 6, 15, and 16. The average baseline MSCEIT total score was 86.57±1.668, which then decreased to 82.00±2.574 at the 8-week follow-up (p = 0.124). The score changes of HDRS-24 and its items were found uncorrelated to the score changes of MSCEIT and its components at the 8-week follow-up.

Conclusions

This research has the potential to contribute significantly to refining rTMS treatment strategies for patients with mood disorders, which may lead to enhanced clinical outcomes.
COMPARATIVE EFFICACY OF ELECTROCONVULSIVE THERAPY, TRANSCRANIAL MAGNETIC STIMULATION AND OTHER NOVEL PHARMACOLOGICAL APPROACHES FOR THE ACUTE TREATMENT OF MAJOR DEPRESSIVE EPISODES IN ADULTS: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Hsieh Yu-Wen , Liu *Tinghui
Published: February 2025

Background

Major depressive episodes can severely impair daily functioning and quality of life, making it crucial to identify the most effective treatments. Electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and novel pharmacological approaches are increasingly used but have not been comprehensively compared.

Objectives

The aim of this network meta-analysis is to compare the efficacy of ECT, TMS, and ketamine for the acute treatment of major depressive episodes in adults.

Methods

A systematic review and network meta-analysis were carried out following the PRISMA guidelines. We systematically searched the PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) published up to September 2023. Our primary outcome of interest was the reduction in depression scale scores. To ensure the quality of the included studies, we exclusively considered RCTs involving adult human participants and published as peer-reviewed articles, with a specific focus on head-to-head comparative studies.

Results

In our analysis, we included a total of 13 randomized controlled trials (RCTs) involving 599 patients to evaluate the reduction in depression scale scores. Among the specific interventions compared, ECT demonstrated the highest efficacy, with a statistically significant reduction in depression scale scores compared to TMS (Standardized Mean Difference (SMD): 0.07, 95% Confidence Interval (CI): 0.01 to 0.69). However, when compared to ketamine, there was no statistically significant difference observed (SMD: 0.07, 95% CI: 0.00 to 1.19). Notably, ketamine also showed a significant reduction in depression scale scores compared to TMS (SMD: 0.90, 95% CI: 0.02 to 35.96). Among these interventions, ECT had the highest probability of being the most effective treatment, with a surface under the cumulative ranking value of 91.2.

Conclusion

Our network meta-analysis suggests that ECT is the most effective acute treatment for major depressive episodes in adults, followed by ketamine.
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

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

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

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<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

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

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

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

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

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<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<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 <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.