bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFICACY OF THE NOVEL 5-HT1A RECEPTOR AGONIST DSP-1181 ON OBSESSIVE-COMPULSIVE DISORDER LIKE BEHAVIOR IN A MOUSE MODEL OF OPTOGENETIC NEURAL MODULATION
Authors: Sato *Fumiaki , Nagano Yusuke , Tachibana Daiki , Ikeda Hiroko , Imai Hideaki , Yamashita Tomomi , Okuyama Makiko , Tajima Junko , Asada Reiko , Fukumoto Kenichi 
Published: February 2025

Abstract

Background
Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by the presence of obsessions and compulsions, leading to significant impairment in social and occupational functioning. The current first-line treatment for OCD involves the use of selective serotonin reuptake inhibitors (SSRIs). However, SSRIs typically take several weeks to show therapeutic effects in OCD patients, and they are ineffective in approximately 40% of cases. Thus, there is a need for new drugs with rapid action and high efficacy. The 5-HT1A receptor has been implicated in various psychiatric symptoms, including anxiety. Additionally, previous studies have reported the clinical efficacy of 5-HT1A receptor agonists in alleviating OCD symptoms. Therefore, we discovered a novel 5-HT1A receptor agonist called DSP-1181, which possesses a distinct profile compared to previously approved agonists of the same receptor.

Aims & Objectives
Our aim was to investigate whether DSP-1181 ameliorates OCD-like behavior in a mouse model using optogenetics to evaluate its potential as a novel therapeutic agent for OCD.

Method
We carried out the marble-burying behavior test on naï ve male ICR mice. In the test, 20 glass marbles were placed equidistant from each other on the bedding. Each animal was left for 15 minutes in a cage. At the end of the test, the number of buried marbles covered with bedding was counted. We utilized optogenetics to bilaterally activate the orbitofrontal cortex-ventromedial striatum projections in male C57BL/6J mice to create a non-clinical model (OCD mice) that reflects the neural hyperactivation observed in OCD patients. The grooming time of the mice was measured for a 5-minute period, starting 1 hour after a 5-minute stimulation session.

Results
In the marble-burying behavior test, the number of buried marbles significantly decreased following administration of the novel compound DSP-1181, similar to clinically effective drugs such as the SSRI escitalopram and the 5-HT1A receptor agonist buspirone. In OCD mice, the grooming time was significantly increased compared to control virus-injected mice. A single administration of DSP-1181 was sufficient to decrease the increased grooming time observed in OCD mice. In contrast, repeated administration of either escitalopram or buspirone was required to suppress the grooming time.

Discussion & Conclusion
This study demonstrated that DSP-1181 exerted its rapid anti-OCD effect in multiple behavioral tests including well-validated OCD mice. These findings suggest that 5-HT1A receptor agonists hold promise as a potential treatment for OCD.
PROLINE-RICH TRANSMEMBRANE PROTEIN 2 KNOCK-IN MICE PRESENT NIGROSTRIATAL DOPAMINERGIC HYPERACTIVITY AND INCREASED SUSCEPTIBILITY TO L-DOPA-INDUCED MOTOR DEFICITS
Authors: Hatta *Daisuke , Kanamoto Kaito , Makiya Shiho , Watanabe Kaori , Kishino Tatsuya , Fuchigami Yuki , Kawakami Shigeru , Kinoshita Akira , Yoshiura Koh-Ichiro , Kurotaki Naohiro , Shirotani Keiro , Iwata Nobuhisa 
Published: February 2025

Abstract
Mutations of proline-rich transmembrane protein 2 (PRRT2) lead to dyskinetic and convulsive disorders such as paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile seizure and hemiplegic migraine. PKD is characterized by attacks of involuntary movements precipitated by suddenly initiated motion. Previous studies have shown that PKD might be caused by cerebellar dysfunction; however, considering widespread expression of Prrt2 in the whole brain, it is likely that some other motor-related regions including the basal ganglia, where dopaminergic neurons are most abundant in the brain, might also be a part of pathogenesis of PKD. Here, we generated Prrt2 knock-in (KI) mice harboring mutation c.672dupG that mimics the human pathological mutation c.649dupC and investigated the role of Prrt2 in the basal ganglia. The mutant transcript and protein were abolished within the striatum, confirming loss-of-function nature of PKD and related disorders. Importantly, intrastriatal microdialysis revealed that the Prrt2 mutation dramatically elevated extracellular dopamine levels during the depolarized state, which might result from the increase in dopamine release because pharmacological inhibition of dopamine reuptake produced a greater elevation of extracellular dopamine levels in Prrt2-KI mice than in wild-type mice. Moreover, administration of L-dopa, a precursor of dopamine, exacerbated rotarod performance of Prrt2-KI mice more severely than that of wild-type mice. Overall, these findings suggest that dopaminergic dysfunction within the basal ganglia by the PRRT2 mutation might be implicated in a part of motor symptoms of PKD and related disorders.
THE SPATIAL COGNITIVE DYSFUNCTION AND MICROGLIAL ACTIVATION INDUCED BY ADOLESCENT SOCIAL ISOLATION THROUGH THE HYPOPRODUCTION OF CYSTINE BY THE DAMAGE OF COLONIC GOBLET CELLS
Authors: Tanabe *Moeka , Kunisawa Kazuo , Saito Imari , Kosuge Aika , Tezuka Hiroyuki , Kawai Tomoki , Hasegawa Masaya , Kubota Hisayoshi , Saito Kuniaki , Nabeshima Toshitaka , Mouri Akihiro 
Published: February 2025

Abstract

Background
Adverse experiences such as bullying and abuse in adolescence increase the risk of developing psychiatric diseases in adulthood. However, it is poorly understood how adverse experiences lead to the pathogenesis of psychiatric diseases. Intestinal homeostasis in the gut-brain axis is susceptible to adolescent stress.

Aims & Objectives
In the present study, we investigated whether an adolescent social isolation (SI) after weaning induces behavioral abnormalities through disrupted colonic function.

Method
After mice were exposed to SI (isolation from 3 to 7 weeks of age), the gut microbiota was analyzed by metagenomic analysis in feces. Spatial memory function was evaluated by a novel object location test in SI-exposed mice. Metabolomic analysis in serum was analyzed by liquid chromatography-mass spectrometry (LC-MS).

Results
Adolescent mice exposed to SI showed spatial memory dysfunction in the novel object location test, and activation of microglia in the hippocampus (HIP). Interestingly, SI decreased the differentiation of goblet cells which produce mucin. The composition of gut microbiota was also altered by SI. Particularly SI depleted Akkermansia muciniphila (A. muciniphila) feeds on mucin. The decrease of goblet cells by SI reduced homocysteine-related metabolites in serum. The administration of rebamipide, which promotes the differentiation of goblet cells in the colon, attenuated SI-induced not only the impairment of spatial memory, the activation of microglia in the HIP, but also the decrease of cystine, a downstream metabolite of homocysteine. Interestingly, the serum cystine levels correlated with spatial memory function. Further, the administration of cystine ameliorated not only SI-induced spatial memory impairment, but also microglial activation and increase of microglial C-C motif chemokine ligand 7 (CCL7) in the hippocampus.

Discussion & Conclusion
These findings suggest that adolescent SI decreased serum cystine level via damage of colonic goblet cells resulting in the spatial cognitive deficits and microglia activation in the hippocampus.
RE-EXAMINATION OF PSYCHIATRIC DISORDERS FROM THE VIEWPOINT OF ANTIPSYCHOTIC-INDUCED ENCEPHALOPATHY
Authors: Hayama *Satoshi A 
Published: February 2025

Abstract

Background
There is inadequate understanding of chronic encephalopathy as one of the irreversible side effects of antipsychotics.

Aims & Objectives
The objective of this study was to identify clinical picture and to re-examining psychiatric disorders.

Method
Inquiries were sent to patients and lawyers, researchers were interviewed, and information was used from the literature.

Results
15 years-old male, diagnosed wrongly as schizotypal personality. Haloperidol 10mg/day or levomepromazine, sulpiride, imipramine had taken for two years. After starting the medicine, insomnia worsened, Parkinsonism, catalepsy, prodromal stage of Neuroleptic malignant syndrome(NMS) appeared. MRI revealed cortical atrophy scattered each cerebral lobes toward the periphery(fig). Cerebral fissure and sulcus enlarged. Cerebral ventricle did not enlarge. Electroencephalography has revealed brain waves in the second stage of sleep during arousal.
The 2nd case 48 years-old female. After the hysteromyoma operation, anxiety and hysteria appeared. The doctor gave haloperidol, 2.4mg [ /day ] 100 days, Chlorpromazine and diazepam were used together. Extrapyramidal syndrome, including Parkinson’ s syndrome appeared. Hypermyotonia and WAIS decreases from standard levels to 60. She had confined to bed for 3 years because of her tiredness of the brain after withdrawal of haloperidol. In acute stage, marked extrapyramidal symptom, anxiety, and mild dementia. In the chronic stage, they could only perform work for a short period of time due to mental exhaustion accompanied by heavy-headedness and became bedridden because of cerebral exhaustion, similar to chronic fatigue syndrome.

Discussion & Conclusion
It is the important viewpoint for re-examining the schizophrenic brain why antipsychotics heal the schizophrenic brain but destroy the normal brain. A normal brain is characterized by the orderly execution of neuronal activity, which is comprised of gene expression, impulse transmission, and neural circuits. Schizophrenia occurs when this orderly process disintegrates, resulting in the disruption of normal neural activity. Malignant neoplasm neural circuits are associated with the pathogenesis of schizophrenia. They occur independently of native neural circuits to generate the false self. Although the neurons located on the brain surface are already at the sleep level, the neurons located in the deep layers of the cerebral cortex are still active about EEG. The possibility that a reduction in continuity between neural circuits leads to insomnia is discussed.

References
Chandran. M and El-Shazy. M (2009), “Catatonia, neuroleptics and brain damage-a case report”, J Psychophamacol, Vol.23 No.2, pp.223-226
VALUABLE INTERACTION WITH COGNITIVE REMEDIATION AND OPTIMAL ANTIPSYCHOTICS FOR RECOVERY IN SCHIZOPHRENIA (VICTORY-S): STUDY PROTOCOL FOR AN INTERVENTIONAL, OPEN-LABEL, RATER- BLINDED, RANDOMIZED COMPARISON OF COMBINED TREATMENT WITH COGNITIVE REMEDIATION AND LURASIDONE OR PALIPERIDONE
Authors: Kubota *Ryotaro , Ikezawa Satoru , Oi Hideki , Oba Mari S , Izumi Shoki , Adachi Leona , Miwa Mako , Tsuno Ryoko , Toya Shunji , Nishizato Yohei , Haga Daisuke , Iwane Tatsuro , Nakagome Kazuyuki 
Published: February 2025

Abstract

Background
Cognitive impairment, a core feature of schizophrenia, is associated with poor functional outcomes. Available interventions include both pharmacotherapy and psychosocial treatment. However, each of these interventions, when used alone, have often inadequate effect sizes.

Aims & Objectives
This study aims to compare the effects of lurasidone combined with cognitive remediation (the Neuropsychological Educational Approach to Remediation [NEAR]) and paliperidone combined with NEAR on cognitive function in patients with schizophrenia.

Methods
The valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia (VICTORY-S) study is a multicenter, interventional, open-label, rater-blinded, randomized comparison study, comparing the effect of lurasidone plus cognitive remediation with that of paliperidone plus cognitive remediation in patients with schizophrenia. The NEAR will be used for cognitive remediation. Eligible patients will be randomized 1:1 to receive lurasidone or paliperidone combined with NEAR (6 weeks antipsychotic alone followed by 24 weeks combination antipsychotic plus NEAR). The primary endpoint is the change from baseline in the tablet-based Brief Assessment of Cognition in Schizophrenia composite T-score at the end of the 24-week NEAR combination treatment period. Secondary endpoints will include change from baseline in various measures of social function, positive and negative symptoms, depression, defeatist beliefs, and quality of life at the end of the 24- week NEAR combination treatment period. Furthermore, change from the end of the 6-week antipsychotic alone period to the end of the 24-week NEAR combination treatment period will be assessed for all endpoints. Safety will also be evaluated. (Japan Registry of Clinical Trials ID is jRCTs031200338)

Results
This study is currently recruiting participants.
Discussion & Conclusion: Achievement of adequate cognitive function is central to supporting social function, which is one of the key treatment goals for patients with schizophrenia. A previous study investigated the combined effect of lurasidone and cognitive remediation in patients with schizophrenia. However, cognitive function had recovered by the start of cognitive remediation and there was no antipsychotic control. We think that this study will fill in the gaps of the previous study and provide useful information to clinicians regarding treatment decisions for patients with schizophrenia.
CHILDHOOD EMOTIONAL MALTREATMENT INCREASES THE “WEAR-AND- TEAR” OF PHYSIOLOGICAL SYSTEMS, ESPECIALLY NEUROENDOCRINE CHANGES IN SCHIZOPHRENIA
Authors: Wang *Ran , Xu Shuqi , Yang Xue , Jiao Lihuan 
Published: February 2025

Abstract

Background
A body of experimental data and clinical investigations suggests that childhood adversity permanently affects the plasticity of multiple brain circuits, including the processing of environmental stimuli, the regulation of autonomic nervous, cardiovascular and endocrine responses.

Aim
To quantify the “wear and tear” on physiological systems in schizophrenia, we introduced the concept of allostatic load (AL) index,which covers multiple physiological indicators and is a useful framework for predicting stress-related dysbiosis. Adverse childhood experiences, especially sexual and emotional abuse, could lead to elevated levels of AL index in patients with schizophrenia. We aimed to determine whether childhood trauma affects physiological indicators of schizophrenia in adulthood, particularly indicators of stress. Improved understanding of the relationship between childhood maltreatment and stress- related pathophysiology could strengthen multidisciplinary interventions and further comprehensive the healthcare system for people with schizophrenia.

Method
Using the Childhood Trauma Questionnaire (CTQ) and the allostatic load (AL) index. First-episode drug-naï ve schizophrenia patients (n=56) and healthy controls (n=53) were evaluated. Pearson correlation analysis was employed to explore the relationship between childhood traumatic experiences and the AL index in schizophrenia patients.

Results
Schizophrenia patients exhibited significantly higher scores for childhood trauma compared to healthy controls. Emotional abuse was found to correlate positively with the neuroendocrine-related AL index in schizophrenia patients (r=0.471, p&lt;0.001). Multivariate linear regression further confirmed that emotional abuse was a significant predictor for the neuroendocrine-related AL index, accounting for 20.6% of its variance.

Conclusion
The findings of this study suggest that emotional abuse during childhood is associated with an elevated neuroendocrine-related AL index in adulthood among patients with schizophrenia. This offers new insights for clinical assessment and intervention in schizophrenia.
ACUTE AND CHRONIC EFFECT OF ESSENTIAL OIL BLEND ON PHYSIOLOGICAL RESPONSE OF STRESS
Authors: Saiyudthong *Somrudee , Chansiri Kosum , Lee Brian , Sittiprapaporn Phakkharawat , Sathirachawan Kanchanapa 
Published: February 2025

Abstract

Background
Prolonged stress is a major cause of mental and physical illness (Mariotti A, 2015). Aromatherapy, using essential oil, has been widely used to relieve stress (Farrar AJ and Farrar FC, 2020).

Aims & Objectives
The aim of this study was to investigate the effects of Thai aromatherapy formulations, including bergamot oil, ylang-ylang oil, Litsea cubeba Pers. oil, peppermint oil and sandalwood oil on relaxation.

Method
Firstly, essential oil formulation used for reducing stress was developed in order to choose the most satisfying blend. The selected blend was identified the main component by using gas chromatography mass spectrometry (GC– MS). Then, this blend was used to investigate the acute effect of essential oil inhalation on physiological stress by assessing vital sign, salivary α-amylase and salivary cortisol. Subsequently, the effect of long-term treatment with stickers made with the selected blend was investigated.

Results
The result showed that the volunteers were satisfied with the essential oils blend containing menthol, isomenthone and limonene. Acute inhalation of this blend did not lower blood pressure including systolic blood pressure, diastolic blood pressure and mean arterial pressure, heart rate, salivary α-amylase and salivary cortisol level compared to pre- inhalation. After 2 weeks of using sticker containing essential oil blend, there was a significant reduction in stress score, systolic blood pressure and salivary cortisol (p&lt;0.05).

Discussion & Conclusion
This study indicated that long-term inhalation of Thai essential oil blend reduced stress by reducing the hypothalamic-pituitary-adrenal axis (HPA) activity.

References
Mariotti, A. (2015) ‘The effects of chronic stress on health: new insights into the molecular mechanisms of brain– body communication’ Future Sci OA., 1(3), Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137920/pdf/fso-01-23.pdf (Accessed: 30 October 2023).
Farrar AJ, Farrar FC. (2020) Clinical Aromatherapy. Nurs Clin North Am. 2020 Dec;55(4): pp. 489- 504. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520654/pdf/main.pdf (Accessed: 10 September 2020).
BIDIRECTIONAL RELATIONSHIP BETWEEN DISABILITY AND COGNITIVE IMPAIRMENT: A LONGITUDINAL STUDY AMONG TAIWANESE OLDER ADULTS
Authors: Hung *Tsung-Hsuan , Tsai Tsung-Yu , Chiu Ching-Ju 
Published: February 2025

Abstract

Background
Cognitive impairment and disability are two significant age-related health issues in older adults, but the relationship between each other remains unclear. Several cross-sectional studies have established the associations between cognitive impairment and disability. While the previous longitudinal studies reported inconsistent results.

Aims & Objectives
We aim to simultaneously explore the relationship between cognitive impairment and disability and further pinpoint which one holds a more pivotal role in the relationship.

Method
628 participants aged 66.0 (SD=7.3) were retrieved from the Social Environment and Biomarkers of Aging Study, a nationally representative longitudinal survey of Taiwanese study, conducted in 2000. Cognition was evaluated by using a modified Short Portable Mental Status Questionnaire (SPMSQ), and disability was indicated by Activity of daily living (ADL), Instrumental activity of daily living (IADL), and Mobility. Structural equation models with cross-lagged analysis were performed for path analysis.

Results
The cross-lagged model was well constructed (χ2 (9)=34.5941, p&lt;0.0001, RMSEA=0.0673, CFI=0.99, SRMR=0.03). Baseline disability in 2000 significantly predicted future cognitive impairment (β=−0.25, p&lt;0.05) in 2006, and baseline cognitive impairment in 2000 also significantly predicted future disability (β=−0.03, p&lt;0.05) 6 years later. Fisher’ s Z test, examining difference of the standardized coefficients from two cross-lagged paths, showed statistically significance(p&lt;0.001).

Discussion & Conclusion
The findings suggested the relationships between cognition and disability are bidirectional in older adults. Compared to the impact of cognitive function on disability, disability presented a greater influence on subsequent cognitive impairment. The potential mechanisms of such kinds of associations might be complicated. To explain the mechanism, future research, focusing on comorbidities, physical and mental capacities, social interactions, unhealthy lifestyles, and the inflammation process, is warranted.
Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study
Authors: Schuiveling Mark , Ter Maat Laurens S , Van Duin Isabella A J , Verheijden Rik J , Troenokarso Max F , Moeskops Pim , Verhoeff Joost J C , Elias Sjoerd G , Van Amsterdam Wouter A C , Burgers Femke , Van Den Berkmortel Franchette W P J , Boers-Sonderen Marye J , Boomsma Martijn F , De Groot Jan Willem , Haanen John B A G , Hospers Geke A P , Piersma djura , Vreugdenhil Gerard , Westgeest Hans M , Kapiteijn Ellen , Labots Mariette , Veldhuis Wouter B , Van Diest Paul J , De Jong Pim A , Pluim Josien P W , Leiner Tim , Veta Mitko , Suijkerbuijk Karijn P M 
Published: February 2025

Abstract

Introduction
The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to investigate body mass index (BMI) alongside CT-derived body composition metrics in the largest cohort to date.

Methods
Patients treated with first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma centers in The Netherlands. From baseline CT scans, five body composition metrics were extracted: subcutaneous adipose tissue index, visceral adipose tissue index and skeletal muscle index, density and gauge. These metrics were correlated in uni- and multivariable Cox proportional hazards analysis with progression-free, overall and melanoma-specific survival (PFS, OS and MSS).

Results
A total of 1471 eligible patients were included. Median PFS and OS were 9.1 and 38.1 months, respectively. Worse PFS was observed in underweight patients (multivariable HR = 1.86, 95% CI 1.14–3.06). Furthermore, prolonged OS was observed in patients with higher skeletal muscle density (multivariable HR = 0.88, 95% CI 0.81-0.97) and gauge (multivariable HR = 0.61, 95% CI 0.82-0.998), whereas higher visceral adipose tissue index was associated with worse OS (multivariable HR = 1.12, 95% CI 1.04-1.22). No association with survival outcomes was found for overweight, obesity or subcutaneous adipose tissue.

Discussion
Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with improved OS. These associations were independent of known prognostic factors, including sex, age, performance status and extent of disease. No significant association between higher BMI and survival outcomes was observed.