bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRAMIPEXOLE AS A TARGETED ADJUNCTIVE TREATMENT FOR ANHEDONIA IN DEPRESSION: RESULTS FROM AN EXPLORATORY PILOT STUDY
Authors: Lindahl *Jesper Henrik , Ventorp Filip , Van Westen Danielle , Jensen Jimmy , Björkstrand Johannes , Lindqvist Daniel 
Published: February 2025

Abstract

Background
Anhedonia is a common persisting state among depressed patients, associated with treatment resistance and increased loss of function. There are currently no specific and effective treatments for anhedonia. Previous trials have indicated that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed for clinical implementation. Given its mechanism of action, pramipexole might be efficacious for a depression subtype characterized by significant anhedonia and lack of motivation, symptoms associated with dopaminergic hypofunction.

Aims and Objectives
The objective was to investigate feasibility and target engagement of high dose, add on pramipexole treatment in anhedonic depression, as well as exploring biomarkers as predictors of treatment response, using a transdiagnostic design and several indicators of treatment efficacy.

Method
Twelve patients with unipolar or bipolar, moderate to severe depression, and significant anhedonia were included in this open label pilot study. All patients were on a stable dose of antidepressants and or mood stabilizers and received ten weeks of adjunctive pramipexole titrated to a maximum dose of 4,5 mg salt per day. Patients were rated with the Dimensional Anhedonia Rating Scale, the Montgomery Asberg Depression Rating and the Snaith Hamilton Pleasure Scale. Pre and post treatment analyses of high sensitivity C reactive protein were performed. Related Samples Wilcoxon signed rank test was used to investigate changes in symptom severity and hsCRP. Eight patients underwent fMRI pre and post treatment, and the monetary incentive delay task was used to investigate the effect on striatal activity during reward anticipation.

Results
DARS, MADRS and SHAPS scores all improved significantly over ten weeks of pramipexole treatment, p under 0,01. Mean levels of hs CRP decreased significantly over the course of treatment from mean 3,56 mg per litre at baseline to 2,61 mg per litre at endpoint, p under 0,01. There were significant treatment associated increases in reward related activity in several brain areas including the right lateral putamen, anterior left caudate, left posterior putamen, right dorsal caudate, left anterior putamen, and the right nucleus accumbens.

Discussion and Conclusion
This is the first study to suggest efficacy and target engagement of pramipexole in anhedonic depression and these preliminary findings could help inform future large-scale randomized controlled trials to test predictors of treatment response, advancing the field of precision psychiatry.

References
1.Howland 2008
2.Argyropoulos and Nutt 2013
3.Pelizza and Ferrari A 2009
4.Uher et al 2012
5.Barone et al 2010
6.Tundo et al 2019
7.Fawcett et al 2016
8.Treadway et al 2019
FACTORS ASSOCIATED WITH LONGITUDINAL DECREASE IN DOSES OF BENZODIAZEPINE HYPNOTICS IN PATIENTS WITH DEPRESSIVE DISORDERS
Authors: Sakai *Yoshiyuki , Ishii Junpei , Kodaka Fumitoshi , Mori Keisuke , Kobayashi Tamayo , Kameyama Hiroshi , Yamadera Wataru , Shigeta Masahiro 
Published: February 2025

Abstract

Background
The development of orexin receptor antagonists (ORAs) has become an alternative choice of pharmacotherapy for patients with sleep disorders. A previous prescription database (JP4DR) survey of patients who visited the Department of Psychiatry, The Jikei University Hospital in 2018 and 2020 showed a significant decrease in the diazepam equivalent dose of benzodiazepine (BZ) hypnotics in patients with psychiatric disorders. However, the factors associated with the decrease in patients with depressive disorders remain unclear. The study was approved by the Ethics Committee of the Jikei University School of Medicine.

Aims and Objectives
In the present study, we investigated the factors associated with the decrease in the dose of BZ hypnotics in patients with depressive disorders.

Method
We selected patients from the prescription database who visited the outpatient section of Department of Psychiatry, Jikei University Hospital from December 1 to 31, 2018 and from December 1 to 31, 2021. These patients were diagnosed with ICD-10 codes F32 (depressive episode) and F33 (recurrent depressive disorder). We compare doses of diazepam equivalents of BZ hypnotics, imipramine equivalent doses of antidepressants, and the doses of ORAs in 2018 and 2021. A multiple regression analysis was performed to examine the association of longitudinal changes in diazepam equivalent doses of BZ hypnotics between 2018 and 2021 with changes in the equivalent dose of imipramine, the dose of suvorexant, and the dose of lemborexant. The significance level was set at 5%.

Results
877 patients with psychiatric disorders had visit the Department of Psychiatry, Jikei University Hospital on both December 1-31, 2018 and 2021. Of those, 246 patients with F32 (depressive episode) and F33 (recurrent depressive disorder) were included in the analysis. The diazepam equivalent doses of BZ hypnotics decreased significantly between 2018 and 2021 (p = 0.01). Multiple regression analysis showed that a decrease in imipramine equivalents of antidepressants was associated with a decrease in BZ hypnotics (p&lt;0.01).

Discussion and Conclusion
The decrease in the diazepam equivalent dose of BZ hypnotics was significantly associated with the decrease in the imipramine equivalent dose of antidepressants. It is suggested that improvement in depressive symptoms and comorbid insomnia led to the decrease in antidepressant medication.
TREATMENT FOR ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD) DRUG NORMALIZES AIS LENGTH ABNORMALITY ALONG WITH HYPERACTIVITY IN PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP)-DEFICIENT MICE
Authors: Iwahashi *Misaki , Yoshimura Takeshi , Harigai Wakana , Takuma Kazuhiro , Hashimoto Hitoshi , Katayama Taiichi , Hayata-Takano Atsuko 
Published: February 2025

Abstract

Background
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder (NDD) with three characteristics: hyperactivity, inattention, and impulsivity. Although the number of patients with ADHD has increased in recent years, its pathology remains unclear. The axon initial segment (AIS) is a region of the proximal axon, which is responsible for information output by generating action potentials. Recent studies have shown that the structure of AIS can be altered based on the input to the neuronal circuit, and the alteration can impact neural activity. We have previously observed an abnormality of AIS length in rodent models of ADHD and autism spectrum disorder. However, the relationship between AIS length abnormality and pathology of NDDs is still unknown.

Aims & Objectives
In this study, we examined whether PACAP-deficient (PACAP–/–) mice, which display ADHD-like behaviors show AIS length abnormalities. Further, we examined the effects of atomoxetine (ATX), an ADHD drug, on the AIS length in PACAP–/– mice.

Method
Brain sections were prepared from both PACAP–/– and wild-type mice and immunohistochemically stained with anti-Ankyrin-G antibody to stain AIS, and then the three-dimensional length of each AIS was traced and measured using Imaris software. We administered ATX dose or saline to both mice for 2 weeks. After that, we conducted the open field test, and then by immunohistochemical staining of mouse brain sections with anti-Ankyrin-G antibody to stain the AIS.

Results & Discussion
PACAP–/– mice exhibited abnormal Ankyrin-G-stained AIS lengths in layer 2/3 neurons of the S1BF. In addition, repeated ATX treatment effectively normalized abnormal AIS length in PACAP–/– mice along with improvement of hyperactivity. These results suggest that AIS abnormalities are one of the phenotypes of ADHD. This study is the first piece of evidence to indicate drug-mediated improvement in AIS length in the brains of ADHD animal models. Our findings provide novel insight into the potential contribution of the AIS to the pathology of NDDs.

References
1)Iwahashi et al., (2023) J Pharmacol Sci. 153(3):175-182.
RELATIONSHIPS BETWEEN SCHIZOPHRENIA SEVERITY AND INFLAMMATORY BIOMARKER: NEUTROPHIL/LYMPHOCYTE RATIO, MONOCYTE/LYMPHOCYTE RATIO, PLATELET/LYMPHOCYTE RATIO
Authors: Kim *Ho Chan , Kim Seong Hwan 
Published: February 2025

Abstract

Background
Neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) are inflammatory biomarkers. Potential of these inflammatory biomarkers as state marker of schizophrenia severity is controversial.

Aims & Objectives
This study aimed to investigate the relationship between inflammatory biomarkers and schizophrenia severity.

Method
From January 2010 to June 2020, the medical records of schizophrenia patients admitted to Kosin University Gospel Hospital were retrospectively examined and 91 patients who met the inclusion criteria were selected as the subjects of the study. The Korean version of the Positive and Negative Syndrome Scale (PANSS-KV) was used to assess schizophrenia symptom severity and divided into PANSS- KV total score (PANSS-T), PANSS-KV positive syndrome subscale (PANSS-P), PANSS-KV negative syndrome subscale (PANSS-N), PANSS-KV general psychopathology subscale (PANSS-G).

Results
In 91 subjects, 40 were men and 51 were women. We found no significant relationship between sex, age, number of hospitalization and NLR, MLR, PLR. Patients with higher NLR, MLR, PLR had higher PANSS-T scores. Positive correlation between NLR, MLR, PLR and PANSS-N, PANSS-G was demonstrated. There was no significant correlation between NLR, MLR, PLR and PANSS-P.

Discussion & Conclusion
We investigate the possibility of inflammatory biomarkers as state markers of schizophrenia symptom severity. A well-designed prospective study involving a larger cohort is needed in the future.
EFFECT OF SUB-CHRONIC INTERLEUKIN-17A ADMINISTRATION FOR MICE ON PREPULSE INHIBITION TEST USING ACOUSTIC STARTLE STIMULI
Authors: Wakabayashi *Chisato , Kunugi Hiroshi 
Published: February 2025

Abstract

Background
It is well known that proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17A concentration is increased in the plasma of schizophrenic patients. These cytokines have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating abnormalities. However, the mechanisms underlying the involvement of these cytokines have not yet well been studied.

Aims & Objectives
The aim of this study is to examine whether IL-17A induces sensorimotor gating deficits in mice. We also examined whether IL-17A administration affected GSK3α/β protein level or phosphorylation in mouse striatum.

Method
Recombinant mouse IL-17A (low-dose: 0.5 ng/mL and high-dose: 50 ng/mL with 10 μ L/g mouse body weight, respectively) or vehicle was intraperitoneally administered into C57BL/6 male mice 10 times in 3 weeks (sub-chronic administration). Prepulse inhibition (PPI) test using acoustic startle stimulus was conducted 4 weeks after the final IL-17A administration. We evaluated the effect of IL-17A administration on protein level or phosphorylation of GSK3α/β in the striatum by Western blot analysis.

Results
Sub-chronic IL-17Administration induced significant PPI deficits even at 4 weeks later. The deterioration of PPI was observed with dose dependent. Low-dose of IL-17A administration significantly decreased both GSK3α (Ser21) and GSK3β (Ser9) phosphorylation in mouse striatum. There was no significant alteration of GSK3α/β protein levels except for GSK3α in low-dose IL-17A administration group. High-dose of IL-17A, however, did not any alteration of GSK3α/β phosphorylation or protein level in striatum.

Discussion & Conclusion
We demonstrated for the first time that sub-chronic IL-17A administration induced PPI disruption. This result means that the previous exposure to IL-17A may well induce subsequent PPI reduction in the future. The confusing result was that high- and low-dose of IL-17A showed different effect in phosphorylation or protein level of GSK3α/β at the striatum. We considered the existence of other molecules that might be selectively affected in a high doses IL-17 environment. Further analysis including other brain regions will be needed.
This study was accepted for publication in the Neuropsychopharmacology Reports journal this year.

References
Wakabayashi C, Kunugi H. Possible involvement of Interleukin-17A in the deterioration of prepulse inhibition on acoustic startle response in mice. Neuropsychopharmacol Rep, 43(3):365–372 (2023)
BREXPIPRAZOLE AS ADJUNCTIVE THERAPY FOR BORDERLINE PERSONALITY DISORDER : A CASE REPORT
Authors: Danasasmita *Febrianti Santiardi 
Published: February 2025

Abstract

Background
Borderline personality disorder (BPD) is a severe, difficult-to-treat psychiatric disorder that causes significant emotional distress as well as a significant financial burden on health-care systems.
BPD is distinguished by a pervasive pattern of affective instability, difficulty with impulse control, and aggressive outbursts. Although psychotherapy has been shown to reduce BPD symptoms, not all patients can tolerate it. Medication research is ongoing, but no drug has been approved by FDA for the treatment of BPD. 1-2Brexpiprazole is a novel serotonin-dopamine activity modulator with partial agonist activity at 5-HT1A and D2/D3 receptors and strong antagonist activity at 5-HT2A, a1B, and a2C adrenergic receptors. Furthermore, given the low rates of side effects reported in clinical trials for other disorders to date, brexpiprazole should be well tolerated in people with BPD. 2-3

Aims & Objectives
The case report discusses the use of brexpiprazole as new generation antipsychotic in reducing BPD’ s symptom.

Method
Miss Z, 20 years old female, university student, reported that she was drunk alcohol excessively to cope with her anxiety. Moreover, she had self-harm behaviour to overcome her negative thought. She felt emptiness and difficult to describe her emotion chronically. She reported low motivation to go to school, unable to enjoy her activity, difficulty of sleep. Furthermore, she reported low self-esteem and perceived burdensomeness. She was afraid of abandoned by her boyfriend. Although her boyfriend had cheated on her, she tried to be with him. That made her self-esteem became worse. Besides her activity as a student, she had a part-time job as a model. She took great care of her weight and appearance. She was given escitalopram 10 mg once daily and brexpiprazole 1 mg half a day. After taking the medication for 8-weeks, her emotion improves. She had good quality of sleep, reduction of self-harm behaviour and came back to school.

Results
Brexpiprazole appears to have some effect on the symptoms of BPD.

Discussion and Conclusion
Although the neurobiology of BPD is not fully understood, it appears to involve dysfunctions in the serotoninergic and dopaminergic systems. Brexpiprazole is partial agonist activity at 5-HT1A and D2/D3 receptors. As a result, they may be uniquely positioned to help with both mood symptoms and reward processing in BPD.

References
1.Diagnostic and statistical manual of mental disorders : DSM-5-TR / American Psychiatric Association. Copyright © 2022 American Psychiatric Association
2.Grant JE, Valle S, Chesivoir E, Ehsan D, Chamberlain SR. A Double-Blind, Placebo-Controlled Study of Brexpiprazole in the Treatment of Borderline Personality Disorder. Br J Psychiatry. 2022 February ; 220(2): 58–63. doi:10.1192/bjp.2021.159.
3.Del Casale A, Bonanni L, Bargagna P, Novelli F, Fiasche F, Paolini M. et al., Current Clinical Psychopharmacology in Borderline Personality Disorder. Curr Neuropharmacol.2021 Oct 18; 19(10): 1760–1779.
COMMENSAL GUT MICROBE MODULATES STRESS-INDUCED GUT DYSMOTILITY THROUGH GUT-DERIVED METABOLITES AND SYMPATHETIC NERVOUS SYSTEM
Authors: Tsai *Yu-Hsuan , Wu Wei-Li 
Published: February 2025

Abstract

Backgroud
Stress is a pivotal environmental risk factor for the development of mental disorders. While the impact of stress can vary among individuals, gut dysmotility is a common characteristic in response to acute stress. Mounting evidence suggests that the commensal microbiota residing in the gut plays a crucial role in modulating gut motility. Recent investigations have highlighted the ability of gut microbiota to influence tryptophan metabolism, thereby impacting gut motility. Moreover, studies investigating the gut-brain axis have revealed that the absence of gut microbiota leads to activation of gut-innervated sympathetic neurons. Intriguingly, our previous research demonstrated that colonization of specific commensal gut bacteria, Enterococcus (E.) faecalis, in microbiome-depleted mice can suppress the hypothalamic-pituitary-adrenal (HPA) axis, thereby regulating the release of the stress hormone corticosterone. This pathway exhibits a close association with stress, which has been shown to significantly affect gut motility.

Aims & Objectives
Despite the recognition of the gut microbiota as a crucial regulator of the gut-brain axis, the precise mechanisms through which specific microbes in the intestine remotely influence the HPA axis remain unclear. In this study, we hypothesize that commensal gut microbe modulates stress-induced gut dysmotility via colonic tryptophan metabolism and the sympathetic nervous system.

Method
To investigate this hypothesis, we established an experimental model of acute stress exposure in mice colonized with specific commensal microbes and evaluated their stress response by assessing gut motility.

Results
Our findings indicate that E. faecalis selectively restores gut dysmotility and corticosterone levels following stress exposure, both of which are profoundly disrupted by gut microbiota depletion. Furthermore, metabolomic profiling of serum after microbiota depletion and E. faecalis colonization revealed alterations in metabolites involved in tryptophan and tyrosine metabolisms, accompanied by changes in the expression of key rate-limiting enzymes associated with these pathways. Immunostaining of c-Fos demonstrated that colonization of E. faecalis diminishes neural activity in brain regions implicated in the HPA axis and autonomic nervous system following acute stress exposure, including the paraventricular nucleus of the hypothalamus (PVN), area postrema (AP), and lateral paragigantocellular reticular nucleus/rostral ventrolateral medulla (LPGi/RVLM). Lastly, administration of E. faecalis to mice with complete microbiome effectively restores stress-induced gut dysmotility.

Discussion & Conclusion
Collectively, our findings provide valuable insights into the intricate mechanisms by which intestinal bacteria influence the host through the gut-brain axis and strongly suggest a novel mechanism through which intestinal commensal bacteria regulate the host's stress response and its subsequent consequences.
A STUDY ON THE REGULATORY STATUS OF PSYCHEDELICS IN KOREA AND THEIR ADMISSIBILITY AS THERAPEUTIC AGENTS
Authors: Sohn *Inki , Jeong Jong-Hyun 
Published: February 2025

Abstract

Background
Korea has strict controls on narcotics. Nonetheless, as the impact of research on the therapeutic use of marijuana, psychedelics, etc. discussions on their medical use are beginning in Korea.

Aims & Objects
The author intends to consider the possibility and necessary steps for allowing the medical use of psychedelics through a comparison of major countries' medical narcotic designation principles and a historical review of the legalization of medical use of marijuana in Korea.

Method
Governance of regulatory agencies for narcotics in Korea was reviewed. Literature related to drug designation criteria in major countries was reviewed. Reviewed the legalization process for medical use of marijuana in South Korea

Results
Compared to major countries, Korea has the strictest drug designation standards. In particular, foreign regulatory cases are the main reference standard. This is similar to the process of determining approval for pharmaceuticals in the Korean Food and Drug Administration. It can be said that the conservative regulatory authority's stance that allows medical use only when all are certified in each country is reflected in the designation of narcotics for medical use. Governance for medical narcotics in Korea is under the Ministry of Food and Drug Safety's drug safety officer and Drug Safety Bureau. Each has an independent decision-making process. Distribution of medical narcotics, which are different from treatment purposes, is the main route of abuse/dependence. In Korea, there is a nationwide surveillance system (patient medication history confirmation system and big data-based surveillance system) for prescribed narcotics drugs, which is a protective factor for abuse/dependence. Through the historical review of the process of legalization and acceptance of medical use of marijuana, which has been designated as a narcotic, but is partially permitted for medical use, prospects for the acceptance process of medical use of psychedelics have been made.

Discussion & Conclusion
Regulatory practices and socio-political conservative tendencies regarding the acceptance of drugs for human use are barriers to the acceptance of psychedelics for medical use. For the relaxation of this regulation, permitting the medical use of hallucinogens in major countries is a prerequisite. However, a national monitoring system for medical narcotic drug use is an advantageous condition for persuading regulatory authorities for the clinical use of psychedelics as therapeutics.
Digital health equity frameworks and key concepts: a scoping review
Authors: Kim Katherine K , Backonja Uba 
Published: February 2025

Abstract

Objectives
Digital health equity, the opportunity for all to engage with digital health tools to support good health outcomes, is an emerging priority across the world. The field of digital health equity would benefit from a comprehensive and systematic understanding of digital health, digital equity, and health equity, with a focus on real-world applications. We conducted a scoping review to identify and describe published frameworks and concepts relevant to digital health equity interventions.

Materials and Methods
We conducted a scoping review of published peer-reviewed literature guided by the PRISMA Extension for Scoping Reviews. We searched 5 databases for frameworks related to or applied to digital health or equity interventions. Using deductive and inductive approaches, we analyzed frameworks and concepts based on the socio-ecological model.

Results
Of the 910 publications initially identified, we included 44 (4.8%) publications in our review that described 42 frameworks that sought to explain the ecosystem of digital and/or health equity, but none were comprehensive. From the frameworks we identified 243 concepts grouped into 43 categories including characteristics of individuals, communities, and organizations; societal context; perceived value of the intervention by and impacts on individuals, community members, and the organization; partnerships; and access to digital health services, in-person services, digital services, and data and information, among others.

Discussion
We suggest a consolidated definition of digital health equity, highlight illustrative frameworks, and suggest concepts that may be needed to enhance digital health equity intervention development and evaluation.

Conclusion
The expanded understanding of frameworks and relevant concepts resulting from this study may inform communities and stakeholders who seek to achieve digital inclusion and digital health equity.