bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROLE OF NEUROINFLAMMATION IN THE PANIC-EVOKING EFFECT OF HYPOXIA IN RATS
Authors: Zangrossi Jr *Helio , Silva Jefferson Nascimento , Hernandes Paloma Molina , Gomes Arthur Rocha , De Lisboa Sabrina Souza 
Published: February 2025

Abstract

Background
Exposure to high CO2 or low O2 levels can evoke panic attacks in humans and panic-like escape behavior in rodents1,2. Accumulating evidence indicates that neuroinflammation is a key factor linking environmental stress to the development of psychiatric illness such as post-traumatic stress disorder and depression3. However, the role of neuroinflammation in panic disorder, and more specifically in the genesis of panic attacks, remains unclear.

Aims and Objectives
We here investigated the effects of exposing rats to hypoxia (7% O2) on microglia activation in two key panic-associated areas, the dorsal periaqueductal gray (dPAG) and dorsal raphe nucleus lateral wings (lwDRN). We also explored the effects of lipopolysaccharide (LPS), a potent immune activator, or minocycline, an inhibitor of microglia activation, on the expression of escape behavior during exposure to hypoxia. LPS was also administered in the neonatal period and its behavioral consequences during the hypoxia challenge was investigated in early adulthood.

Methods
In experiment 1, immunofluorescence staining for Iba-1 was used to track microglial activation. In experiment 2, LPS (0,1 mg.kg-1, i.p.) or minocycline (30 or 60 mg.kg-1, 5 days, i.p.) were injected 24 hs and 30 min before the hypoxia challenge, respectively. In experiment 3, LPS (0.05 mg.kg-1, ip) was injected on postnatal day 14 (PND 14) and rats were submitted to hypoxia on PND 60.

Results
Hypoxia exposure caused a marked increase in Iba-1 immunofluorescence both in dPAG and lwDRN and this was observed 6 and 24 hs, but not 1 h after the respiratory challenge. While administration of LPS in the adulthood or on PND14 facilitated the expression of escape response, a panicogenic-like effect, minocycline caused the opposite effect.

Discussion and Conclusions
The results suggest that neuroinflammatory changes are implicated in pathophysiology of panic-attacks. They also indicate that early hyperactivation of the immune system can increase susceptibility to panic attacks.

Acknowledgements
Fapesp, CNPq and Faepa, Brazil

References
1Spiacci A Jr, Sergio Tde O, da Silva GS, et al. Serotonin in the dorsal periaqueductal gray inhibits panic- like defensive behaviors in rats exposed to acute hypoxia. Neuroscience. 307:191-8, 2015.
2Nardi AE, Valenç a AM, Mezzasalma MA, et al. 35% Carbon dioxide and breath-holding challenge tests in panic disorder: a comparison with spontaneous panic attacks. Depress Anxiety. 23(4):236–44, 2006.
3Pape, K., Tamouza, R., Leboyer, M. Zipp, F. Immunoneuropsychiatry — novel perspectives on brain disorders. Nat. Rev. Neurol. 15, 317–328, 2019.
THE GUT MICROBIOTA MODULATE LOCOMOTION VIA VAGUS-DEPENDENT GLUCAGON-LIKE PEPTIDE-1 SIGNALING
Authors: Lai *Tzu-Ting , Tsai Yu-Hsuan , Liou Chia-Wei , Fan Ching-Hsiang , Hou Yu-Tian , Yao Tzu-Hsuan , Chuang Hsiao-Li , Wu Wei-Li 
Published: February 2025

Abstract

Background
Locomotor activity is an innate behavior that can be triggered by gut-motivated conditions, such as appetite and metabolic condition. Various nutrient-sensing receptors distributed in the vagal terminal in the gut are crucial for signal transduction from the gut to the brain. The levels of gut hormones are closely associated with the colonization status of the gut microbiota, suggesting a complicated interaction among gut bacteria, gut hormones, and the brain. However, the detailed mechanism underlying gut microbiota-mediated endocrine signaling in the modulation of locomotion is still unclear.

Aims & Objectives
We hypothesize that the vagus-dependent enteroendocrine signaling serves as a mediator for the gut microbiome to modulate locomotor behavior.

Methods
To assess the association among gut microbiome, gut hormone glucagon-like peptide-1 (GLP-1) levels, and locomotion in mice, we depleted the gut microbiome by administrating the cocktail of a broad- spectrum antibiotic (ABX) in the drinking water for C57BL/6J mice and tested for their locomotor activity. The brain, serum, and fecal samples were analyzed by immunohistochemistry staining, ELISA, and 16S rRNA sequencing, respectively. On the other hand, the vagus nerve is one of the promising neural connections bidirectionally innervating in the GI tract and the brain. The subdiaphragmatic vagotomy (SDV) and transcranial focused ultrasound (FUS) was performed to understand the contributions of gut- associated vagal signaling involved in the microbiota-mediated GLP-1-induced locomotion alteration.

Results
Herein, we show that ABX-treated mice displayed hypolocomotion and elevated levels of the gut hormone GLP-1. Blockade of the GLP-1 receptor and subdiaphragmatic vagal transmission rescued the deficient locomotor phenotype in ABX-treated mice. Activation of the GLP-1 receptor and vagal projecting brain regions led to hypolocomotion. Finally, selective antibiotic treatment dramatically increased serum GLP- 1 levels and decreased locomotion. Colonizing Lactobacillus reuteri and Bacteroides thetaiotaomicron in microbiota-deficient mice suppressed GLP-1 levels and restored the hypolocomotor phenotype.

Discussion & Conclusion
Our findings identify a mechanism by which specific gut microbes mediate host motor behavior via the enteroendocrine and vagal-dependent neural pathways.
BTRX-246040 ACTS THROUGH THE VENTROLATERAL PERIAQUEDUCTAL GRAY TO EXERT ANTIDEPRESSANT-RELEVANT ACTIONS IN MICE
Authors: Li *Zhenlong , Xu Yuanyuan , Li Rourou , Sheng Zhenyu , Liu Xueman , Lee Chau-Shoun , Peng Hsien-Yu , Lin Tzer-Bin , Hsieh Ming-Chun , Lai Cheng-Yuan , Wu Han-Fang , Chou Dylan 
Published: February 2025

Abstract

Background
BTRX-246040, a nociceptin/orphanin FQ peptide receptor antagonist, is being developed for the treatment of depressive patients[1,2]. However, the underlying mechanism of this potential antidepressant is still largely unclear. Here, we studied the antidepressant-related actions of BTRX- 246040 in the ventrolateral periaqueductal gray (vlPAG).

Methods
The tail suspension test, forced swim test, female urine sniffing test, sucrose preference test, and learned helplessness (LH) combined with pharmacological approaches were employed to examine the antidepressant-like effects and drug effects on LH-induced depressive-like behavior in C57BL/6J mice. Electrophysiological recordings in vlPAG neurons were used to study synaptic activity.

Results
Intraperitoneal administration of BTRX-246040 produced antidepressant-like behavioral effects in a dose dependent manner. Systemic BTRX-246040 (10 mg/kg) resulted in an increased frequency and amplitude of miniature excitatory postsynaptic currents (EPSCs) in the vlPAG. Moreover, slice perfusion of BTRX-246040 directly elevated the frequency and amplitude of miniature EPSCs and enhanced the evoked EPSCs in the vlPAG, which were blocked by pretreatment with the nociceptin/orphanin FQ peptide receptor agonist Ro 64-6198. In addition, intra-vlPAG application of BTRX-246040 produced antidepressant-like behavioral effects in a dose-dependent manner. Moreover, intra-vlPAG pretreatment with 6-cyano-7-nitroquinoxaline-2,3-dione reversed both systemic and local BTRX-246040– mediated antidepressant-like behavioral effects. Furthermore, both systemic and local BTRX-246040 decreased the LH phenotype and reduced LH-induced depressive-like behavior.

Conclusions
The results suggested that BTRX-246040 may act through the vlPAG to exert antidepressant-relevant actions. The present study provides new insight into a vlPAG-dependent mechanism underlying the antidepressant-like actions of BTRX-246040.

References
[1]Post, A., Smart, T., Krikke-Workel, J. et al. A Selective Nociceptin Receptor Antagonist to Treat Depression: Evidence from Preclinical and Clinical Studies. Neuropsychopharmacol 41, 1803–1812 (2016).
[2]Witkin J.M., Wallace T.L., Martin W.J. Therapeutic approaches for NOP receptor antagonists in neurobehavioral disorders: clinical studies in major depressive disorder and alcohol use disorder with BTRX-246040 (LY2940094). Handb Exp Pharmacol 254, 399–415 (2019).
EVALUATING PSYCHOLOGICAL DISTRESS ASSOCIATED WITH LIFE EVENTS UNDER THE TRAUMATIC EXPERIENCE THRESHOLD IN PATIENTS WITH MAJOR DEPRESSIVE AND BIPOLAR DISORDER
Authors: Hashimoto *Tasuku , Ishii Hiroki , Sato Aiko , Tanaka Mami , Seki Ryota , Ogawa Michi , Kimura Atsushi , Iyo Masaomi 
Published: February 2025

Abstract

Background
Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience psychological distress associated with daily events that do not meet the threshold for traumatic experiences, referred to as event-related psychological distress (ERPD). Recently, we developed an assessment tool for ERPD, the ERPD-24, consisting of four factors: feelings of revenge, rumination, self-denial, and mental paralysis.

Aims & Objectives
The purpose of this study was to clarify the features of ERPD in patients with MDD and BD.

Method
We conducted a cross-sectional study between March 2021 and October 2022 to identify the differences and clinical features of ERPD among patients with MDD and BD and healthy subjects who did not experience traumatic events. Specifically, we assessed ERPD using the ERPD-24 and anxiety-related symptoms with the State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, and anxious- depressive attack. We used a one-way analysis of variance test to compare differences among the groups, followed by a post hoc test.

Results
Non-remitted MDD patients and BD patients regardless of remission/non-remission presented more severe ERPD than healthy subjects. This study also demonstrated the relationships between all anxiety-related symptoms including social phobia and anxious-depressive attack and ERPD in both BD and MDD patients and in healthy subjects.

Discussion & Conclusion
In conclusion, patients with non-remitted MDD and with BD regardless of remission/non-remission experience severe ERPD related to anxiety-related symptoms.

Figure Legend
ERPD-24 scores (total and sub-categories: revenge, rumination, self-denial, mental paralysis) for the 6 groups: depressive bipolar disorder (BD), manic/hypomanic BD, remitted BD, depressive major depressive disorder (MDD), remitted MDD, and healthy subjects (HS). Comparison between BD-mania or hypomania and HS (p &lt;0.05); † Comparison between BD-depression and MDD- depression (p &lt;0.05); ‡ Comparison between BD-depression and MDD-remission (p &lt;0.05); § Comparison between BD-depression and HS (p &lt;0.05); || Comparison between BD-remission and HS (p &lt;0.05); ¶ Comparison between MDD-depression and HS (p &lt;0.05); ** Comparison between BD-mania or hypomania and r BD-depression (p &lt;0.05).

References
Event-Related Psychological Distress Scale- 24 (ERPD-24) explained in this URL&lt;https://www.m.chiba- u.ac.jp/class/psy3/education/erpd24.html&gt;
NETWORK STRUCTURE OF INTERPERSONAL SENSITIVITY IN PATIENTS WITH MOOD DISORDERS: A NETWORK ANALYSIS
Authors: Kim *Yuna , Park Jungkyu , Myung Woojae 
Published: February 2025

Abstract

Background
Interpersonal sensitivity, characterized by heightened awareness of others' behavior and emotions, is linked to mood disorder. However, a comprehensive analysis of how some items of Interpersonal Sensitivity Measure (IPSM) interrelate and contribute to the overall construct.

Aims & Objectives
We conducted a network analysis using IPSM items to comprehend interpersonal sensitivity in patients with mood disorders. The objectives were to 1) explore the network structure of interpersonal sensitivity in patients with mood disorders (MDD, bipolar I disorder [BD I], and bipolar II disorder [BD II]) and 2) identify the central symptoms of interpersonal sensitivity.

Method
IPSM, a 36-item self-report scale, was utilized to evaluate interpersonal sensitivity symptoms in 837 participants (MDD, n = 265; BD I, n = 126; and BD II, n = 446). We performed exploratory graph analysis, employing regularized partial correlation models to estimate the network structure. Centrality analysis identified core IPSM symptoms for each mood disorder group. Network comparison tests assessed structural differences between the MDD and BD subgroups.

Results
Network analysis detected five communities. Item 10 (“I worry about being criticized for things that I have said or done”) showed the highest value in strength. Multiple items on "negative self-image" and "anxiety related to social approval" showed high strength centrality. Network structure invariance and global strength invariance test results indicated no significant differences between the MDD and BD subgroups.

Discussion & Conclusion
Our findings emphasize the importance of addressing "negative self-image" and "anxiety related to social approval" in the IPSM network among mood disorder patients based on core items of the network. Also, targeted treatments and comprehensive strategies in this aspect could be crucial for managing mood disorders.
MANIC BEHAVIOR MAY BE ATTENUATED BY MATRIX METALLOPROTEINASE-8 INHIBITOR VIA DECREASING NEUROINFLAMMATION IN A MOUSE MODEL OF BIPOLAR DISORDER
Authors: Wang *Tzu-Yun , Wang Shao-Ming 
Published: February 2025

Abstract

Background
Emergent evidence showed that neuroinflammation may be involved in the pathogenesis of bipolar disorder (BD). Ouabain, a Na+/K+-ATPase inhibitor, is used to induce BD in animal models [1] and is associated with neuroinflammation and glial cell activation [2]. Our previous study showed that ouabain treatment in astrocytes may increase matrix metalloproteinase (MMP)-8 expression.

Aims & Objectives
In the present study, we investigated whether the MMP-8 inhibitor, M8I, could control neuroinflammation and reduce manic-like behavior in an ouabain-induced BD animal model.

Method
Ouabain was intracerebroventricular (ICV) injected in mice to induce manic-like behavior in the open field test and tail suspension test. Pretreatment of M8I (5 mg/kg) or control medium was given before the 7th day of ouabain ICV injection. We then measured the behavior change and the activation pattern of astrocytes and microglia in the frontal cortex and hippocampus in ouabain-induced BD mice with M8I or control medium pretreatment.

Results
0.625 nmol of ouabain ICV administration induced manic-like behavior in mice with increased locomotor activity both shown in the open field test and tail suspension test. Immunofluorescence in the hippocampal CA1 region showed an increased activation of astrocytes and microglia in ouabain-treated mice. Notably, pretreatment with M8I may reduce hyperactivity in the tail suspension test and attenuate the overactivation of astrocytes and microglia.

Discussion & Conclusion
Our study suggested neuroinflammation may have a key role in the pathogenesis of bipolar disorder, especially in the manic symptoms. The manic-like behavior may be attenuated by M8I via suppressing overactivated microglia and astrocytes in the hippocampus. Further studies to investigate the potential roles of M8I in treating depressive behavior in the ouabain-induced BD animal model may be warranted.

References
1.Valvassori, S.S., et al., Validation of the animal model of bipolar disorder induced by Ouabain: face, construct and predictive perspectives. Transl Psychiatry, 2019. 9(1), 158.
2.Kurauchi, Y., et al., 2018. Na(+), K(+)-ATPase inhibition induces neuronal cell death in rat hippocampal slice cultures: Association with GLAST and glial cell abnormalities. J Pharmacol Sci, 2018. 138(3), 167- 175.
OVEREXPRESSION OF SHATI/NAT8L IN THE HIPPOCAMPUS AMELIORATES COGNITIVE DYSFUNCTION IN MODEL MICE WITH ALZHEIMER’ S DISEASE
Authors: Izuo *Naotaka , Ikejima Daiki , Chino Kakeru , Asano Takashi , Kuboyama Tomoharu , Tohda Chihiro , Muramatsu Shin-Ichi , Nitta Atsumi 
Published: February 2025

Abstract

Background
Shati/Nat8l was identified as an upregulated molecule in the nucleus accumbens of mice with repeated administration of methamphetamine. We have reported the role of this molecule in psychiatric disorders such as depression as well as drug dependence.

Aims & Objectives
The purpose of this study was to investigate the role of Shati/Nat8l in cognitive function. For this purpose, we evaluated the cognitive function of the mice with hippocampus-specific knockdown of Shati/Nat8l on wildtype and Alzheimer’ s disease (AD) model mice with hippocampus-specific overexpression of Shati/Nat8l.

Method
Hippocampus-specific Shati/Nat8l knockdown mice were generated by local microinjection of an adeno- associated virus (AAV) vector for the Cre expression into the hippocampus of Shati-flox mice (7 weeks old, male). AD model mice with hippocampus-specific overexpression of Shati/Nat8l were generated by local microinjection of AAV vectors for expression Shati/Nat8l into the hippocampus of 5xFAD mice (6 weeks old, male), which overproduces amyloid-β. These mice were used for experiments after 4 weeks from AAV vector administration.

Results
Mice with hippocampus-specific Shati/Nat8l knockdown showed cognitive dysfunction in a novel object recognition test. In the acute slices of these mice, a marked suppression of synaptic long-term potentiation in the CA1 region induced by θ-burst stimulation of the hippocampal Schaffer's lateral branch was observed. 5xFAD mice exhibited decreased hippocampal expression of Shati/Nat8l and cognitive dysfunction. Hippocampus-specific overexpression of Shati/Nat8l improved cognitive dysfunction in 5xFAD mice. In these mice, no alterations of amyloid β accumulation or neurodegeneration in the hippocampus were observed, whereas the expression of BDNF, a neurotrophic factor, was increased.

Discussion & Conclusion
These results indicate that hippocampal Shati/Nat8l is important for cognitive function. For AD pathology with the reduction of hippocampal Shati/Nat8l, genetic supplementation of Shati/Nat8l could be an effective therapeutic strategy for the treatment of cognitive dysfunction.
SEASONALITY OF HOSPITALIZATION FOR ALCOHOL USE DISORDERS: A CROSS-SECTIONAL STUDY IN CHINA
Authors: Zhang *Kai , Yao Yitan , Chen Chuanchuan , Yang Qiongyao , Wang Yue , Zhang Miaomiao , Wang Wenhui , Zhong Yongjie , Yuan Xiaoping , Luo Bei 
Published: February 2025

Abstract

Background
Seasonal patterns have been observed in several psychiatric disorders such as depression and schizophrenia, but there is no consensus on the seasonality of alcohol use disorders.

Objectives
We thus retrospectively analyzed a large-scale database to explore whether seasonality affects hospitalization for alcohol use disorders.

Method
In this study, a total of 14,357 inpatients with alcohol use disorders were recruited over a 7- year time span, and after applying rigorous data criteria, 2,176 inpatients were ultimately included in the statistical analysis.

Results
Patients with alcohol use disorders admitted in various seasons had significant differences in length of stay (H=13.592, df=3, P=0.004), and corrected Bonferroni post hoc tests suggested that patients admitted in spring had a shorter length of stay than in the other three seasons (P=0.009, P=0.013, P=0.048 for summer, autumn and winter, respectively). In addition, seasonality may have influenced the relapse of the disease. We found that disease recurrence was unevenly distributed across various seasons (X2=10.486, df=3, P=0.015), with corrected Bonferroni post hoc tests suggested a higher proportion of recurrent admissions in summer(P&lt;0.05). We then performed a Binary logistic regression, and the effect of seasonality on disease recurrence remained significant after controlling for gender, occupation, and marital status. Taking winter as a reference, the risk of relapse was higher in spring and summer (OR=1.284, 95CI%=1.00-1.65, P=0.048; OR=1.393, 95CI%=1.08-1.80, P=0.011, respectively).

Conclusion
This is the first large sample size study to explore the seasonality of hospitalization for alcohol use disorders in a Chinese population. Our study found that patients with alcohol use disorders admitted in the spring had shorter hospital stays, but also had more relapses in the spring and summer. These findings will contribute to the exploration of risk factors for alcohol use disorders as well as provide preliminary evidence for clinical development of prevention strategies.
FACTORS ASSOCIATED WITH LONGITUDINAL DECREASE IN DOSES OF BENZODIAZEPINE HYPNOTICS IN PATIENTS WITH DEPRESSIVE DISORDERS
Authors: Sakai *Yoshiyuki 
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.