bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOLOGICAL EVALUATION OF ANXIOLYTICS AND NICOTINE FOR ANXIETY-RELATED BEHAVIORS AND NEURONAL ACTIVITIES
Authors: Nakahara *Karin , Mouri Akihiro , Kunisawa Kazuo , Hasegawa Masaya , Nabeshima Toshitaka 
Published: February 2025

Abstract

Background
Anxiety is frequently comorbid with peripheral as well as neuropsychiatric diseases. To alleviate the comorbid anxiety, anxiolytics are prescribed, and some people take nicotine through smoking. However, the physiological mechanism of anxiety and how anxiolytics and nicotine relieve it are not well known.
Aims & Objects: To elucidate them, we performed a pharmacological evaluation of anxiolytics (diazepam, fluvoxamine, and tandospirone) and nicotine for the anxiety-related behaviors.

Method
The anxiety-related behaviors were evaluated in the marble burying test (MB), elevated plus-maze test (EPM), social interaction test (SIT), and novelty suppression feeding test (NSF) in an illuminance- dependent manner.

Results
Under the high anxiety illumination, diazepam showed anxiolytic effects on MB, SIT, EPM, and NSF. Fluvoxamine showed anxiolytic effect on MB. Tandospirone showed anxiolytic effects on MB and EPM. Nicotine showed anxiolytic effects on SIT and NSF. To evaluate the effect of anxiolytics and nicotine on the anxiety-related neuronal activity, we measured behavior-related immediate early gene (Arc) expression. Diazepam decreased EPM-related Arc expression in the amygdala but not the prefrontal cortex. However, nicotine did not affect SIT-related Arc expression in the amygdala and the prefrontal cortex.

Discussion & Conclusion
Since diazepam is a positive allosteric modulator of the GABAA receptors, our data suggest that diazepam shows anxiolytic effects on the various behavioral tests by suppression of neuronal activity in the amygdala through GABAergic receptors. Fluvoxamine and tandspiron are a selective serotonin reuptake inhibitor and a 5-HT1A receptor agonist, respectively. Our data suggest fluvoxamine and tandospirone show anxiolytic effect on MB via activation of 5-HT1A receptor. Interestingly, nicotine shows anxiolytic effects on SIT without change of neuronal activity in the amygdala and the prefrontal cortex. The anxiolytic effects of anxiolytics and nicotine were found to be specific to behavioural tests. More detailed assessment of neural activity in different tests will clarify their behavior-specific anxiolytic effects.
EMOTION PROCESSING IN BIPOLAR DISORDER: FASTER REACTIONS, LOWER RECOGNITION
Authors: Ryu *Vin , Nam Hyejin , Oh Yunhye 
Published: February 2025

Abstract
Emotion IAT is a tool that measures an individual's unconscious way of processing emotions. This test asks individuals to quickly associate words that belong to two categories (e.g., "positive" and "negative"). The test results are determined by how quickly the two categories are associated. In this study, we compared 30 euthymic bipolar patients with 30 healthy controls using emotion IAT and facial recognition tests. Facial recognition tests used sadness, happiness, fear, and disgust emotional pictures. In patients with bipolar disorder in remission, there is a tendency to associate positive emotions (p = 0.03) and negative emotions (p=0.02) more quickly on the emotion IAT task than in healthy people. In the facial recognition test, there was no difference between the control group and happiness (p&gt;0.05), but sadness (p=0.03), fear (p=0.02), and disgust (p=0.03) showed poor performance compared to the control group. These results suggest that patients with bipolar disorder have difficulty processing emotions.
This could be related to the symptoms of bipolar disorder. Patients with bipolar disorder tend to be optimistic and impulsive, which suggests that this leads to reduced awareness of negative emotions.
CLINICAL BENEFIT AND UTILITY OF ARIPIPRAZOLE ONCE MONTHLY IN ROUTINE PRACTICE FOR KOREAN BIPOLAR PATIENTS
Authors: Yang *Hyeryun , Moon Ji Wan , Cho Sung Joon , Jeon Sangwon , Shin Young-Chul , Kim Eun Soo 
Published: February 2025

Abstract

Background
Adherence to medication in individuals with bipolar disorder is a crucial factor predicting long-term treatment outcomes. However, the discontinuation rate for Korean bipolar disorder patients over a 3- year period reaches nearly 50%.

Aims & Objectives
While the use of long-acting injectable (LAI) antipsychotic medications is on the rise to improve adherence and manage mood stabilizer side effects, there is a lack of research regarding the functional improvement and therapeutic effects of LAIs in Korean bipolar disorder patients.

Methods
This study is a non-interventional, retrospective, naturalistic observational analysis based on medical records. The starting point for assessing Aripiprazole Once Monthly (AOM) treatment is when it was initiated in routine clinical settings. Data is collected at 1-month, 3-month, 6-month, 9-month, and 12- month intervals using medical records. The primary evaluation variable is the change in the average GAF (Global Assessment of Functioning) score over 12 months, while secondary evaluation variables include changes in scores for YMRS, K-MADRS, HAM-A, dosages of mood stabilizers, antidepressants, antipsychotics, benzodiazepines, anticholinergic medications, and the number of pills.

Results
Analyzing 23 patients the findings reveal that the GAF score increased from 49.8 to 62 over the course of twelve months, with a noticeable increase observed from 1 month of AOM treatment onward (57 points). YMRS exhibited a substantial decrease from 6.7 to 1.4, K-MADRS decreased from 15.5 to 10, and HAM-A dropped from 15.2 to 9.8. There was a significant reduction in and lithium equivalent dosages and pill count for mood stabilizers. Although other medications, including antipsychotics, benzodiazepines, z- drugs, and anticholinergic medications, also saw a decrease in dosages and pills, the changes were not statistically significant. Among the 23 patients, 6 reported side effects (4 cases of akathisia, 3 of tremors, 3 of weight gain, and 1 of headache), but no severe adverse effects were reported.

Discussion & Conclusion
This study demonstrates clinical enhancement in functional outcomes and significant improvement in mood symptoms through AOM treatment in bipolar disorder patients. Moreover, the noteworthy decrease in dosage and pill count for mood stabilizers suggests a potential reduction in side effects for patients. This study holds significance as it is the inaugural evaluation of AOM's utility among Korean bipolar disorder patients.
PREDICTIONS OF DEPRESSION AND SEXUAL STIGMA FOR MOTIVATION TO VACCINATE AGAINST COVID-19 AMONG YOUNG ADULT LESBIAN, GAY AND BISEXUAL INDIVIDUALS: A FOUR-YEAR FOLLOW-UP STUDY
Authors: Yen *Cheng-Fang 
Published: February 2025

Abstract

Background
Vaccination is one of important ways to prevent contracting COVID-19. Predictors of motivation to vaccinate against COVID-19 among lesbian, gay, and lesbian (LGB) individuals have been seldom studied.

Aims & Objectives
The aims of the present study were to examine the predictive effects of depression and the experiences of sexual stigma (i.e., perceived sexual stigma from family members, internalized sexual stigma, and sexual microaggression) before the COVID-19 pandemic on motivation to vaccinate against COVID-19 among LGB individuals four years later during the COVID-19 pandemic in Taiwan.

Method
The baseline data of depression and sexual stigma were collected in 2018 and 2019. Depression was assessed using the Center for Epidemiologic Studies Depression Scale. Perceived sexual stigma from family members was assessed using the Homosexuality-Related Stigma Scale. Internalized sexual stigma was assessed using the Measure of Internalized Sexual Stigma for Lesbians and Gay Men. Sexual microaggression was assessed using the Sexual Orientation Microaggression Inventory. Participants’ motivation to vaccinate against COVID-19 during the COVID-19 pandemic were surveyed using the 9-item Motors of COVID-19 Vaccination. The associations of depression and sexual stigma at baseline with motivation to vaccinate against COVID-19 at follow-up were examined using multivariate linear regression analysis.

Results
Internalized sexual stigma was negatively associated with motivation to vaccinate against COVID-19, whereas sexual microaggression was positively associated with motivation to vaccinate against COVID-19. Depression and perceived sexual stigma from family members were not significantly associated with motivation to vaccinate against COVID-19. Although being male and older age were positively associated with greater motivation to vaccinate against COVID-19, gender and age did not moderate the associations of sexual stigma with motivation to vaccinate.

Discussion & Conclusion
Internalized sexual stigma and sexual microaggression were significantly associated with motivation to vaccinate against COVID-19 with different directions. Intervention strategies for enhancing motivation to vaccinate against COVID-19 in LGB individuals should be developed with consideration of the experiences of sexual stigma.
ABNORMAL STRUCTURAL COVARIANCE NETWORK IN TREATMENT- RESISTANT DEPRESSION
Authors: Tsugawa *Sakiko , Noda Yoshihiro , Honda Shiori , Wada Masataka , Hondo Nobuaki , Moriyama Sotaro , Wannan Cassandra , Zalesky Andrew , Uchida Hiroyuki , Nakajima Shinichiro 
Published: February 2025

Abstract

Background
Treatment-resistant depression (TRD) is associated with gray matter volume reduction compared to healthy controls (HC). Since depression has increasingly been recognized as a disorder of dysregulated neural networks, it is important to evaluate these structural changes in terms of brain networks. Structural covariance is a measurement that gauges the association strength of structural measures between two regions, which is used to examine network-level alteration of brain structure. Although several studies reported abnormal structural covariance in depression, few studies have thus far investigated structural covariance alteration in relation to TRD.

Aims and Objectives
In this study, we aimed to examine structural covariance alteration in TRD compared to HC.

Methods
T1 images were obtained from 116 patients with TRD and 54 HC who were recruited at Keio University. Brain volume was calculated for each of 85 regions of the DK atlas using FreeSurfer 6.0. Group differences in brain volumes were examined by analysis of covariance controlling for age and sex. Structural covariances of brain volumes across 3570 pairs of brain regions were obtained by partial correlation analysis using age, sex, and total intracranial volume as covariates. Network-based statistics were used to extract networks with group differences in structural covariances. This study was conducted after obtaining approval from the respective ethics review committees.

Results
There were no significant differences in brain volumes between the TRD and HC groups. The null hypothesis of equality in structural covariance between them was rejected using network-based statistics. We found a single network comprising connections with elevated structural covariance in patients with TRD compared with HC. The left nucleus accumbens, bilateral pericalcarine, and supramarginal gyrus had high degree centrality in the structural covariance network.

Discussion and Conclusion
Patients with TRD showed coordinated brain volume alterations in comparison with HC, even though there was no difference in brain volumes between them. Nucleus accumbens, an integral hub in the reward circuit, was one of the hubs of extracted network with elevated structural covariance in TRD, which is in line with a previous study that reported higher structural covariance of nucleus accumbens in depression. Further studies are warranted to examine structural covariance differences among TRD, non-TRD, and HC in order to confirm the link between structural alteration and pathophysiology of treatment resistance in depression.
EEG RESPONSE TO HYPERVENTILATION IN PATIENTS USING “EEGHUB.GE”
Authors: Khachidze *Irma , Adcadze Maia , Adamashvili N 
Published: February 2025

Abstract

Introduction
The Big Data EEG (electroencephalogram) collected in Georgia have been integrated and uploaded to the European Open Science Cloud (EOSC). EU Project NI4OS-National Initiatives for Open Science in Europe is funded by the European Commission's Horizon 2020 program. Study EEG by using EEGBUB.GE is aimed to determine the EEG pattern to hyperventilation based on time of onset EEG and age of patients with different CNS disorders. The first online EEG database “EEGHUB.GE” in Georgia was funded and selected as a thematic service and EEG data of patients with NS disfunction. “EEGHUB.GE” is used to study EEG characteristics in Patients with different CNS disorder. There was huge amount of the EEG data, it was necessary to make a database, systematizes and the “EEGHUB.GE” has been created http://eeghub.ge/. It is systematized, curated and stored in an online database in EDF format. The service is free for European and national researchers, based on EOSC FIAR principles Findable, Accessible, Interoperable and Reusable

Methods
Uploaded data’ s ethical side is protected, there are no names and surnames of the patients, instead of they have specific numerical names. New knowledge is required regarding Neurotics issue and uploaded Human EEG database on European ICloud spaces. The project is being implemented by the infrastructure of Georgian Research and Educational Networking Association “GRENA”. The enlarge information about some of the major pathways involved in the epilepsy disease facilitate selection of the most effective & appropriate treatments. Nowadays Hyperventilation is used during the EEG registration and EEG analysis shows a variety of responses, changes, and combinations.

Results
The pathological EEG reaction to hyperventilation was revealed in 985. The patients were split into the following age groups: 3-6, 7-12, 13-18, 19-30, 31-50. Three types of EEG reaction to hyperventilation were revealed in all age-groups of patients: EEG detected the prevalence of disorganization of the basic rhythm(than paroxysmal & epileptiform discharges) in all minutes. In all age groups shown the disorganization of basic EEG rhythm in the first, second and third minutes of hyperventilation. In the first minute was revealed a significant ratio between all types of EEG and age, which was not observed in the second and third minutes.

Conclusion
The extension of functional test is not recommendable, especially in patients with different disorders and in children. EEG-response to hyperventilation based on ages of patients should be taken account for scientific and clinical study.
SAFETY AND EFFICACY OF KARXT IN PATIENTS WITH SCHIZOPHRENIA IN THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED EMERGENT TRIALS
Authors: Kramer *Kenneth , Brannan Stephen K , Sauder Colin , Kaul Inder 
Published: February 2025

Abstract

Background
A high unmet medical need exists for more effective, better tolerated treatments for schizophrenia with novel mechanisms of action. All currently approved treatments for schizophrenia have dopamine D2 receptor blocking activity; the efficacy and tolerability limitations of these therapies are well known. KarXT is a novel combination of the dual M1/M4 preferring muscarinic receptor agonist xanomeline and the peripherally restricted anticholinergic trospium chloride. KarXT is designed to preserve the beneficial central nervous system effects of xanomeline, while mitigating the adverse events observed previously due to peripheral muscarinic receptor activation. In a 5-week, randomized, double-blind, placebo-controlled, phase 2 study (EMERGENT-1; NCT03697252), KarXT met the primary endpoint of a significant reduction in Positive and Negative Syndrome Scale (PANSS), improved other key secondary efficacy measures, and was generally well tolerated.

Methods
EMERGENT-2 (NCT04659161) and EMERGENT-3 (NCT04738123) were 5-week, randomized, double-blind, placebo-controlled phase 3 trials of KarXT in people with schizophrenia with acute psychosis in an inpatient setting. Key inclusion criteria were recent worsening of positive symptoms warranting hospitalization, Positive and Negative Syndrome Scale (PANSS) total score &gt;80, and Clinical Global Impression– Severity (CGI-S) score &gt;4. Eligible participants were randomized 1:1 to KarXT or placebo. KarXT dosing (mg xanomeline/mg trospium) started at 50 mg/20 mg twice daily (BID) and increased to a maximum of 125 mg/30 mg BID. The primary efficacy endpoint was change from baseline to week 5 in PANSS total score. Other efficacy endpoints included change from baseline to week 5 in PANSS positive, PANSS negative, and PANSS Marder negative factor subscale scores.

Results
In the EMERGENT trials, KarXT consistently demonstrated significant and clinically meaningful reductions in Positive and Negative Syndrome Scale (PANSS) score and was generally well tolerated. KarXT demonstrated a significant improvement in other secondary outcome measures, including CGI and PANSS positive subscales, across clinical trials. PANSS negative subscale and PANSS Marder negative factor achieved statistical significance compared with placebo at study endpoint in EMERGENT-1 and 2 and only at week 4 in EMERGENT-3. The most common (&gt;5%) treatment-emergent adverse events with KarXT were all mild to moderate in severity and were not associated with common problematic side effects of current therapies such as motor symptoms, weight gain, prolactin elevation, or somnolence.

Conclusions
If approved, KarXT has the potential to be first in a new class of schizophrenia treatments based on muscarinic receptor agonism and a promising alternative to direct dopamine D2 receptor antagonists and partial agonists.
PROLACTIN LEVEL CHANGES ACCORDING TO ATYPICAL ANTIPSYCHOTICS USE
Authors: Jeong *Jong-Hyun , Sohn Inki , Kim Suhyung , Um Yoo Hyun , Kim Tae Won , Seo Ho-Jun 
Published: February 2025

Abstract

Background
Antipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia.

Aims & Objectives
This study aimed to investigate the levels of serum prolactin elevation depending on the use of antipsychotic drugs in patients through the Clinical Data Warehouse.(CDW)

Method
We conducted a cohort search in the CDW application with the following condition. The subjects who aged more than 18 years old and visited from March 1, 2017, to May 31, 2022 at the Department of St. Vincent’ s Hospital, The Catholic University of Korea. The subjects were diagnosed according to ICD- 10 for schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders. And the subjects who was taking one of risperidone, blonanserin, amisulpride, and olanzapine. The subjects also conducted serum prolactin level tests. After that, we reviewed the medical data.

Results
Among the 117 subjects included in the analysis, the mean serum prolactin level was 64.654.6ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took blonanserin, olanzapine, and risperidone had significantly higher prolactin levels, but there was no difference in serum prolactin levels between the sex in the subjects who took amisulpride.

Discussion & Conclusion
This study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. And we showed that there is a possibility to conduct more effective and simpler big data research using the CDW. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.
BERBERINE REDUCES ANTIPSYCHOTIC-ASSOCIATED WEIGHT GAIN IN SCHIZOPHRENIA PATIENTS WITH LOW-LEVEL LDL: A POOLED ANALYSIS OF RANDOMIZED CONTROLLED TRIAL
Authors: Qin *Zongshi , Wu Jiani 
Published: February 2025

Abstract

Background
MetS thus has become a major concern in the long-term prescription of antipsychotics, as its prevalence is as high as 33.4% in patients with schizophrenia, and it increases diabetic and cardiovascular morbidity and mortality. Berberine is a naturally occurring alkaloid mainly extracted from the Chinese herbal medicine Coptis chinensis. Although berberine has not been licensed for the treatment of metabolic disorders, in vitro and in vivo experimental evidence confirms that berberine has body weight-lowering effects.

Objective
To evaluate the efficacy and safety of berberine as an adjuvant in treating antipsychotic- associated weight gain.

Method
One hundred and thirteen participants with schizophrenia spectrum disorders who had developed metabolic syndrome (MetS) were recruited. They were randomly assigned to berberine (600 mg/day, n=58) or placebo (n=55) groups for 12 weeks. The primary outcome was the change from baseline to week 12 in net weight.

Results
Compared with the placebo group, the berberine group showed a significantly greater reduction in weight gain at 9 weeks (mean difference [MD]=-0.75, 95% confidence interval [CI]: -1.42 to -0.07, P =0.031, d=0.41) and 12 weeks (MD=-1.08, 95% CI: -1.76 to -0.40, P=0.002, d=0.59) in all patients. In the subgroup patients with low-level LDL at baseline (&lt;2.9 mmol/L), there is a larger effect regarding weight gain at 12 weeks (MD=-2.0, 95%CI: -2.8 to -1.0) compared with high-level LDL (MD=-0.3, 95%CI: -1.3 to 0.7). Berberine was well tolerated without serious adverse events and aggravation of psychotic symptoms compared with placebo.

Conclusions
Findings suggest that berberine is effective in attenuating antipsychotic-associated weight gain and MetS, especially for patients with low-level LDL.