bluuebunny/crossref_metadata_2025 huggingface dataset:
IMMUNOLOGICAL GLUTEN SENSITIVITY IN UNDERWEIGHT PATIENTS WITH EATING DISORDER
Authors: Yamada *Hisashi , Mikuni Motoyama , Yoshimura Chiho , Matsunaga Hisato
Published: February 2025

Aims

Gluten sensitivity is a syndrome characterized by several physical and psychological symptoms such as abdominal pain, constipation, diarrhea, headache, foggy brain, tiredness, anxiety, and depression, related to the ingestion of gluten. In recent years, it has been reported that gluten sensitivity is associated with various psychiatric disorders, and anti-gliadin IgG antibodies have been established as a biomarker for gluten sensitivity, but diagnostic criteria have not yet been established and the actual status of gluten sensitivity remains unclear. Eating disorders are psychiatric disorders that are often difficult to treat, especially recovery from low body weight. Low body weight often results in constipation due to decreased gastrointestinal activity, but occasionally patients complain of diarrhea and many patients complain of strong discomfort and physical symptoms after food ingestion. We conducted a study to investigate immunological gluten sensitivity in eating disorder patients with low body weight.

Methods

The subjects were 18 underweight female patients with eating disorders who visited the outpatient clinic of the Department of Psychiatry and Neurology, Hyogo Medical University Hospital and were confirmed to be free from laxative abuse, and 43 age-sex-matched healthy subjects. Blood samples were collected and gluten-related antibodies such as anti-gliadin IgG antibodies were measured by ELISA, and psychiatric and physical symptoms were assessed by interview and self- administered questionnaire. This study was approved by the Ethics Committee of Hyogo Medical University (No. 3412) and written consent was obtained from the subjects.

Results

18 subjects included 10 patients with anorexia nervosa, 7 patients with avoidant restrictive food intake disorder, and 1 patient with other identified eating behavior disorders or eating disorders. In the eating disorder group, the positivity rate of anti-gliadin IgG antibodies was 50%, significantly higher than the 11.6% of the healthy subjects (p=2.3 x 10-3). The antibody positivity rate in patients with diarrhea was 85.7%. Eating disorder patients with immunological gluten sensitivity showed significantly lower mental quality of life, more physical symptoms, and more depressive and anxiety symptoms than the healthy group, but not significantly different from the group without immunological gluten sensitivity. Two patients with anorexia nervosa who were positive for anti-gliadin IgG antibodies were introduced to a gluten-free diet during outpatient care after the discovery of immunological gluten sensitivity and showed clear weight gain.

Conclusion

The relationship of gluten sensitivity in underweight patients with eating disorders is suggested. Considering the pathophysiology of low nutritional status, underweight patients with eating disorders who is more likely to be constipated, but when diarrhea is present, gluten intolerance should be considered.
INPUT AND OUTPUT OF NEUROPEPTIDE Y IN THE NUCLEUS ACCUMBENS AND PALATABLE FOOD INTAKE
Authors: Tanaka *Masaki , Yamada Shunji
Published: February 2025

Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that is widely expressed in the central nervous system and the nucleus accumbens (NAc) is one of the NPY abundant regions as well as arcuate and paraventricular hypothalamic nuclei. NPY in the hypothalamus is well known to enhance food intake. NAc is a hub region of reward and dependence of alcohol and drug intake. We previously suggested that NPY- expressing neurons in the NAc modulate anxiety-behavior using NPY-Cre mice and Cre-dependent AAV. To investigate the projection sites of NAc NPY neurons, we injected AAV(DJ)-FLEX-mCherry into the NAc of NPY-Cre mice. We found mCherry-positive fibers in the lateral hypothalamus (LH), the feeding center. We confirmed this projection to the LH using retrograde tracer. Many NPY nerve fibers are also observed in the NAc. To investigate the origin (s) of NPY fibers in the NAc, we injected AAV(rg)-FLEX- mCherry, permits retrograde access and expression of mCherry to projection neurons, into the NAc in NPY-Cre mice. We found the existence of mCherry-positive cell bodies in the basolateral amygdala (BLA) as well as NAc. Next, we investigated the role of accumbal NPY in the palatable food (high fat diet) intake. We found NPY and NPY Y1 agonist treatment in the NAc induced increase in high fat diet. Then we investigated the involvement of NPY neurons in the BLA projecting to the NAc in high fat diet consumption. Mice stably consume HFD in 1-h during light cycle. To perform projection-specific activation or inactivation of NPY neurons in the BLA, we employed a two-virus strategy, injecting a AAV(rg)-FLEX-Flippase (FLPo) into the NAc and AAV expressing FLPo-dependent hM3Dq-mCherry or - hM4Di-mCherry into the BLA of NPY-Cre mice. CNO-induced activation of BLA NPY neurons projecting to the NAc did not affect to the 1-h HFD intake in the model. On the other hand, CNO-induced inactivation of BLA NPY neurons projecting to the NAc significantly decreased 1-h HFD consumption. These results indicate that NPY neurons in the NAc and those in the BLA that project to the NAc are involved in palatable food consumption in mice.
DNA MICROARRAY ANALYSIS OF GENE EXPRESSION IN THE HYPOTHALAMUS OF SOCIAL-DEFEAT STRESS-INDUCED CHRONIC PAIN MODEL MICE
Authors: Nakamoto *Kazuo , Tokuyama Shogo
Published: February 2025

Background

Exposure to chronic stresses affects the sensitivity to pain stimuli and is associated with the development of chronic pain. However, the molecular mechanisms underlying the pathogenesis of stress-induced chronic pain remain unclear. Our previous study demonstrated that mice subjected to repeated social defeat stress showed a dramatically longer prolongation of postsurgical pain than non- stressed mice.

Aims & Objectives

In this study, we performed DNA microarray analysis within the hypothalamus of these stressed mice to investigate gene expression changes when pain becomes chronic due to stress.

Methods

Male C57BL/6J mice were subjected to social defeat stress for 10 days. The 5 mm incisions were made in the right paw plantar region of the mice as a postoperative pain model. The von Frey test was used to evaluate pain in response to mechanical stimuli. On day 7 of postoperative pain, the changes of gene expression in the hypothalamus tissues were evaluated by DNA microarray analysis. Only genes with expression variation were extracted based on mice subjected to postoperative pain under non-stressed conditions. Genes with a gene expression ratio>2.0 or ratio<0.5 were defined as genes with altered expression.

Results

Nonstress-operation mice showed an increase mechanical allodynia to the 0.16g firmament, which occurred at day 1 post-paw incision and continued for 4 days in comparison with non-stress-sham mice. On the other hand, the mechanical allodynia in stress-operation mice continued for 7 days. At postoperative day 7, DNA microarray analysis revealed that 278 genes were more than doubled in stressed mice with pain, whereas 137 genes were reduced by less than half compared to non-stressed mice.

Discussion & Discussion

These results demonstrated that the main changes included several genes involved in the lipid metabolism, arachidonic acid cascade, inflammatory and immune responses, and hormone. Detailed analysis of the fluctuating genes is currently underway.
KNOWLEDGE AND OPINIONS ABOUT THE USE OF PSYCHEDELICS AMONG PSYCHIATRISTS IN KOREA: PRELIMINARY RESULTS
Authors: Sohn *Inki , Jon Duk-In
Published: February 2025

Background

Psychedelic drugs are substances that have been used for a long time and are legally regulated worldwide because of their hallucinogenic or addictive potential. However, in the 21st century, it began to receive various academic attention because of its promising efficacy beyond the limits of existing drugs.

Aim & Objectives

In this study, a survey was conducted on the knowledge, awareness, and attitude psychiatrists (specialists and residents) about psychedelic drugs in Korea.

Methods

The survey consists of 14 questions regarding knowledge and opinions about psychedelics. 101 doctors participants were currently collected and preliminarily analyzed.

Results

The mean age of participants was 40.5 years old and 72.3% were male. Of them, 44.6% were psychiatric residents and 55.4% were specialists. The average number of correct answers was 2.10 for the five questions regarding knowledge about psychedelics. The difference between two doctor groups was not significant. The question with the highest incorrect answer rate was the selection of classical psychedelics, followed by the associated neurotransmitters. The most recent information obtained about psychedelics were possibility of illicit use and their therapeutic potential. Sources of information about psychedelics were academic conferences, mass media (TV and newspaper), internet searches, peers, and academic articles, in that order. If medical use were to become available, the main concerns were the potential for abuse and the risk of addiction. On the other hand, 56.5% predict psychedelics could be an important treatment in the future, and 63.3% support their authorization for medical use.

Conclusion & Discussion

Psychedelics are gaining global attention and are very promising therapeutic drugs, but our knowledge of them is still low. However, the clinical utility and need for these drugs are highly recognized. We need to continue to spread information through academic conferences and media.
DEMANDS ON MEDICAL PROFESSIONALS AND SOCIETY BY BREAST CANCER PEER SUPPORTERS FROM A HUMAN RELATIONS PERSPECTIVE
Authors: Motoi *Yoshimi , Nagahiro Chie , Hashimoto Yoko , Wakamatsu Chihiro
Published: February 2025

Background and Purpose

Cooperation between cancer patients, medical professionals, and government is essential for achieving cancer peer support. We focused on the perspective of human relations and clarified the demands on medical professionals and society made by breast cancer peer supporters; moreover, we examined future issues.

Methods

Employing qualitative descriptive study, we selected 30 facilities among national cancer patient associations and support groups using a random number table. Consenting representatives from four of these facilities were given explanations of the purpose and methods of this study, and 10 breast cancer peer supporters were interviewed. Data analysis involved categorization using the content analysis method.

Ethical Considerations

This study was conducted with the approval of the ethical review committee to which the research was affiliated (23004). There were no conflicts of interest.

Results

The mean age of participants was 60.8 years (47–73 years), and the mean number of years of experience as a breast cancer peer supporter was 11 years (0.5–20 years), with seven participants having qualifications such as a Breast cancer Experienced Coordinator. The following three categories and eight subcategories were extracted as a result of interviews on participants’ demands of medical professionals and government in their past experiences with breast cancer peer support activities. The wishes of breast cancer peer supporters were the [participation of cancer peer support in team medical care], [improvement of awareness of cancer peer support], and [cooperation between the government and cancer collaboration base hospitals], with the statement of “wanting cancer peer support to be included in team medical care” stated. Additionally, peer support leads to patients’ mental well-being and contributes to the reduced workload of medical professionals; thus, the above statement was found. Moreover, the study also revealed that a system of compensation for peer activities was an urgent issue.

Discussion and Conclusion

Breast cancer peer supporters had a high degree of contribution to the emotional support and literacy improvement of patients and their families from the perspective of human relations. Moreover, they were able to relate to their own experience of how peer support helped them feel better during difficult times. However, this level of recognition was still low, urging the need to understand the activities of breast cancer peer support and for collaboration between cancer patients, medical professionals, and the government to provide team medical care.

References

We would like to thank Editage (www.editage.com) for English language editing.
BLUNTED CORTISOL RESPONSE TO ACUTE PSYCHOSOCIAL STRESS IN WOMEN WITH PREMENSTRUAL DYSPHORIC DISORDER
Authors: Hamidovic *Ajna , Davis John , Soumare Fatimata
Published: February 2025

Background

Despite being considered a stress-related condition, it is not known whether the hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in response to acute psychosocial stress in Premenstrual Dysphoric Disorder (PMDD). This is problematic because many women with PMDD report that they are not able to control their stress levels, and a blunted cortisol output has been identified in women with related psychiatric conditions, such as anxiety and depression.

Aims and Objectives

The present study is a part of the Premenstrual Hormonal and Affective State Evaluation (PHASE) project, and it aimed to characterize the cortisol trajectory in response to an acute psychosocial stress challenge.

Method

Women with PMDD and healthy controls with a confirmed ovulatory cycle underwent the Trier Social Stress Test procedure in the mid-late luteal phase of the menstrual cycle, throughout which we collected serum samples of cortisol that we analyzed using ultra-performance liquid chromatography tandem mass spectrometry.

Results

The linear mixed model analysis indicated a significant time*diagnosis interaction (p=0.008) such that women with PMDD displayed significantly lower serum cortisol levels at +40 through +90 minutes from the time of stress induction.

Discussion and Conclusion

This is the first study to show that women with PMDD have a blunted cortisol response to psychosocial stress. Combined with our earlier finding showing a greater parasympathetic nervous system withdrawal on heart oscillations in PMDD during acute stress, these and other results show that the dysregulated processing of stress in PMDD may be captured using objective study measures.
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

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

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

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

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 <0.05); † Comparison between BD-depression and MDD- depression (p <0.05); ‡ Comparison between BD-depression and MDD-remission (p <0.05); § Comparison between BD-depression and HS (p <0.05); || Comparison between BD-remission and HS (p <0.05); ¶ Comparison between MDD-depression and HS (p <0.05); ** Comparison between BD-mania or hypomania and r BD-depression (p <0.05).

References

Event-Related Psychological Distress Scale- 24 (ERPD-24) explained in this URL
NETWORK STRUCTURE OF INTERPERSONAL SENSITIVITY IN PATIENTS WITH MOOD DISORDERS: A NETWORK ANALYSIS
Authors: Kim *Yuna , Park Jungkyu , Myung Woojae
Published: February 2025

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

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

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

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<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

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<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.
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

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

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

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

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