bluuebunny/crossref_metadata_2025_split huggingface dataset:
SEX DIFFERENCES IN THE REDUCTION OF HOPELESSNESS IN Μ OPIOID RECEPTOR DEFICIENT MICE BY ADDITIVE EFFECTS OF Δ OPIOID RECEPTOR AGONISTS
Authors: Moriya *Yuki , Kasahara Yoshiyuki , Shimada Masafumi , Sakakibara Yasufumi , Fujii Hideaki , Nagase Hiroshi , Ide Soichiro , Ikeda Kazutaka , Hall Frank Scott , Uhl George R , Sora Ichiro 
Published: February 2025

Abstract
Previous pharmacological data have shown the possible existence of functional interactions between μ, κ, and δ opioid receptors in pain and mood disorders. We have reported previously μ opioid receptor knockout (MOP-KO) mice showed a reduced stress responses compared to the wild type (WT) mice.
Moreover, δ opioid receptor (DOP) agonists have been shown to affect antidepressant-like effects in a number of animal models. The tail suspension test (TST) and the forced swim test (FST) were used to examine the roles of MOP and DOP in hopeless emotional effects MOP-KO mice and WT mice were treated with KNT-127, a selective DOP agonist. The results indicated that there was a significant decrease in immobility time in the KNT-127 group compared to the saline group in all genotypes in both tests. In the saline groups, immobility time was significantly decreased in MOP-KO mice compared to WT mice in both tests. In female MOP-KO mice, the results showed that KNT-127 significantly decreased immobility time compared to the WT mice in TST. In male MOP-KO mice, however, TST showed that the KNT-127 or the saline treated do not reduced immobility time for genotype comparisons. Thus, at least in FST and TST, activation of DOP and absence of MOP had additive effects on reducing the hopelessness, suggesting that the lack of motivated behavior by activation of DOP functions independently of MOP.
THE AGE EFFECT UPON FNIRS MEASURED BRAIN FUNCTION BETWEEN SCHIZOPHRENIA PATIENTS AND NORMAL CONTROLS
Authors: Lan *Tsuo-Hung 
Published: February 2025

Abstract

Background
Schizophrenia has been considered as a brain disorder which deteriorates cognitive and social function in affected people. Whether the aging effect will further decline the brain function of schizophrenic patients or not is rarely discussed before.

Aims & Objectives
We here applied fNIRS (functional infrared spectrometry) to measure brain function of schizophrenia to tell the difference from normal with age effect adjustment.

Method
We recruited schizophrenia people and normal controls with different age from 2015 to 2018 with IRB approval in one medical center in central Taiwan. After consent form completed, their brain function performance was measured by using Hitachi ETG 4000 with both centroid and integral data over frontal and bilateral temporal regions channels once. The standard VFT (verbal fluency test) Taiwan version was tested to record the change of oxygenated and deoxygenated hemoglobin reflection curve during the task.

Results
The sample size is 87 for schizophrenic patients and 88 for normal controls. The average integral value of frontal function is lower in people with schizophrenia compared to normal controls, and between group difference is decreasing while people getting older (Fig 1). The average centroid value of frontal function is higher in people with schizophrenia over normal one at any age stage, and the average group gap is increasing by years of aging (Fig 2).

Discussion & Conclusion
The brain function by measuring integral value showed the total working performance during VFT, which showed a greater slope of decline in normal people compared to schizophrenia. However, the reaction lag time after task start during VFT by observing centroid value is prolonged among old people with schizophrenia compared to normal control ones, it might reveal a worse response on cognitive performance for older schizophrenic patients at the same age level. In general, the brain function measured by fNIRS showed a worse outcome in people with schizophrenia compared to normal controls with compatible age level.
THE RISK OF ANTIDEPRESSANT-INDUCED HYPONATREMIA: A META- ANALYSIS OF ANTIDEPRESSANT CLASSES AND COMPOUNDS
Authors: Gheysens Tim , Van Den Eede Filip , De Picker *Livia 
Published: February 2025

Abstract

Background
Hyponatremia (hypoNa) is a potentially serious adverse event of treatment with antidepressants. Previous research suggests that risk of drug-induced hyponatremia differs between antidepressants.1 This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes.

Methods
PubMed and Web of Science were searched for studies reporting on incidence or risk of hypoNa in adults using antidepressants (PROSPERO, CRD42021269801). We modelled random-effects meta- analyses to compute overall incidence and risk of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa incidences. We conducted subgroup analyses for geriatric populations, study context and sodium cut-off value.

Results
We included 39 studies (n = 8,175,125). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (1.911-5.225)). The highest event rates were found for SNRIs (5.31%), SSRIs (5.18%), and TCAs (2.18%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). The highest odds ratios were found for MAOIs (3.789 (1.602 – 8.966)), SNRIs (2.969 (1.717 – 5.136)), and SSRIs (2.842 (1.564 – 5.164)); the lowest for mirtazapine (2.818 (1.886 – 4.211)) and TCAs (1.803 (1.252 – 2.598)). Compared to SSRIs, SNRIs were significantly more likely (k = 9, OR = 1.268 (1.129 – 1.425), p &lt;0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 – 0.957), p = 0.032) associated with hypoNa.

Conclusion
Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

References
1.De Picker L, Van den Eede F, Dumont G, Moorke G, Sabbe BGC. Antidepressants and the Risk of Hyponatremia: A Class-by-Class Review of Literature. Psychosomatics. 2014;55(6):536-47.
ROLE OF KLOTHO ON ANTIDEPRESSANT AND ANTISUICIDAL EFFECTS OF LOW-DOSE KETAMINE INFUSION AMONG PATIENTS WITH TREATMENT-RESISTANT DEPRESSION AND SUICIDAL IDEATION
Authors: Chen *Mu-Hong , Wu Hui-Ju 
Published: February 2025

Abstract

Objective
Previous studies have found an association between klotho, an anti-aging hormone, and major depressive disorder. However, whether low-dose ketamine infusion alters klotho levels among patients with treatment-resistant depression (TRD) remains unknown.

Methods
In total, 48 patients with TRD and strong suicidal ideation were randomly assigned to a single 0.5 mg/kg ketamine or 0.045 mg/kg midazolam regimen and were subjected to a 2-week follow-up. Depressive and suicidal symptoms were assessed before the infusion and during the follow-up. The serum levels of klotho were assessed at baseline and 3 days postinfusion.

Results
A generalized linear model with adjustment of baseline klotho levels showed that, despite the fact that ketamine did not significantly increase levels of klotho, patients in the ketamine group had higher levels of klotho at Day 3 postinfusion than patients in the midazolam group (p = 0.043). However, we found no association between changes in klotho levels and changes in depressive and suicidal symptoms (all p &gt;0.05). Higher klotho levels at baseline were associated with poorer antidepressant effect of low-dose ketamine during postinfusion follow-up.

Discussion
Klotho may play a role in the antidepressant effect of low-dose ketamine. Additional molecular studies are necessary to elucidate the neuromechanisms of TRD, ketamine, and klotho.

References
1.Sartorius et al. Journal of neural transmission. 2019;126:771-776.
2.Chen et al. J Affect Disord. 2023 Aug 12;340:471-475.
HUMAN MICROBIOTA FROM DRUG-NAIVE PATIENTS WITH OBSESSIVE- COMPULSIVE DISORDER DRIVES BEHAVIORAL SYMPTOMS AND NEUROINFLAMMATION VIA SUCCINIC ACID IN MICE
Authors: Shi *Dong-Dong , Zhang Ying-Dan , Wang Zhen 
Published: February 2025

Abstract

Background
Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive- compulsive disorder (OCD).

Aims & Objectives
Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice.

Method & Results
Our study showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota– brain– immune crosstalk.
Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice.

Discussion & Conclusion
We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.
COMPULSIVE SEXUAL BEHAVIOR DISORDER AND IMPULSIVITY
Authors: Weinstein *Aviv , Sassover Eli 
Published: February 2025

Abstract

Background
Compulsive sexual behavior disorder (CSBD) is characterized by extensive sexual behavior and unsuccessful efforts to control excessive sexual behavior. It is a pathological behavior that has compulsive, cognitive and emotional consequences. There is a controversy among researchers and clinicians whether to recognize sex addiction or compulsive sexual disorder and how to classify it. Although hyper-sexuality was proposed for the DSM-V (American Psychiatric Association, 2013), it was not included due to a lack of research into diagnostic criteria for compulsive sexual behavior. The International Classification of Diseases for Mortality and Morbidity Statistics (11th ed.; ICD-11; World Health Organization, 2018) has included CSBD as an impulse control disorder. Recent studies have shown an association between CSBD and impulsivity.

Aims and objectives
to describe our studies and review the evidence for an association of CSBD with impulsivity and to discuss its classification as an impulse control disorder.

Results
We have shown that impulsivity and problematic online use of pornography have been associated with sex addiction. In a further study, participants after 5 year treatment for CSBD, have shown higher ratings of sexual addiction and sexual obsessive-compulsivity than control participants. However, they have demonstrated reduced risk-taking behavior and no evidence for impulsivity indicated by performance on a computerized delay discounting task and the Balloon risk- taking computerized task. In both studies, the positive association between sex addiction, impulsivity and compulsivity supports the notion of an impulsivity-compulsivity spectrum is CSBD. There is contradicting evidence regarding the relationship between CSBD and motor impulsiveness and disinhibition. Individuals with CSBD report that their search after sexuality is often driven by negative emotionality.

Discussion and conclusions
there is contradicting evidence regarding the relationship between CSBD and impulsivity. Currently, there is not enough data supporting CSBD as a behavioral addiction. Further research has to be done, examining CSBD phenomenology as a whole construct and based on a homogeneous criterion.

References
Sassover, E., Weinstein, A. (2020). Should compulsive sexual behavior (CSB) be considered as a behavioral addiction? A debate paper presenting the opposing view. Journal of Behavioral Addictions, 11(2):166–79. doi: 10.1556/2006.2020.00055.
Sassover Eli and Weinstein Aviv. Compulsive sexual behavior disorder and impulsivity In Moustafa Ph.D “The Psychology and Neuroscience of Impulsivity” Elsevier Masson Publishers. In press.
REPRODUCIBLE EFFECTIVE CONNECTIVITY AND ITS RELATIONSHIP TO COGNITION: A SIMULTANEOUS RESTING-STATE PET/MRI INVESTIGATION
Authors: Yang *Kai-Chun , Yang Bang-Hung , Chou Yuan-Hwa 
Published: February 2025

Abstract

Background
Resting-state functional magnetic resonance imaging (MRI) has been widely applied in neuropsychiatric research. However, the functional connectivity it reveals among brain regions could not convey the direction of signaling flow. Although several statistical methods have been developed to infer effective connectivity (EC) for uncovering signaling direction, their utility is constrained by the inherent limitations of relying solely on MRI data. A novel approach, known as metabolic connectivity mapping (MCM), simultaneously acquires positron emission tomography (PET) and MRI data to assess EC. While the EC derived through MCM has been validated, its reproducibility and relationship to cognition remain uncertain.

Aims & Objectives
This study aims to investigate the reproducibility of EC determined by MCM and to explore its functional implications concerning cognition.

Method
We enrolled twenty healthy control participants and acquired resting-state functional MRI and FDG-PET data simultaneously using an integrated scanner at baseline. Eighteen participants underwent a follow- up imaging session one month later. Participants underwent a cognitive assessment probing attention, memory, and executive function at both time points. Group independent component analysis identified four target brain regions: the left middle frontal gyrus, left insula, precuneus, and left angular gyrus.
We employed MCM to evaluate the EC between these brain regions.

Results
Among the twelve pairs of regions assessed for EC, significant EC was observed in seven region pairs at baseline and four region pairs in the follow-up. However, only the bidirectional EC between the precuneus and the left angular gyrus stayed consistent between baseline and follow-up results.
Furthermore, the stronger EC from the left angular gyrus to the precuneus compared to the reverse direction was also reproducible. Notably, the EC from the left angular gyrus to the precuneus positively associated with memory function at both baseline (Standardized β = 0.56, p = 0.04) and follow-up (Standardized β = 0.53, p = 0.04) after controlling age and education level.

Discussion & Conclusion
This study highlights the potential of MCM to explore EC between brain regions. Nevertheless, regional variations in the reproducibility of MCM-derived EC may exist. A comprehensive reproducibility characterization is essential before applying this methodology in future research.
PSYCHOSOMATIC SYMPTOMS IN TYPE 2 DIABETES PATIENTS: A NETWORK ANALYSIS
Authors: Xu *Wei , Jiang Wenhao , Jiang Chenguang , Sun Taipeng , Chen Gang , You Linlin , Cosci Fiammetta , Li Ling , Yuan Yonggui 
Published: February 2025

Abstract

Background
Type 2 diabetes patients display complex psychosomatic symptoms, but the key variables and their interactions remain poorly understood.

Aims & Objectives
We aimed to explore the networks and predictivities among psychosomatic symptoms, demographics, and clinical characteristics of type 2 diabetes.

Method
412 type 2 diabetes patients and 422 healthy controls were recruited. The demographics, the Diagnostic Criteria for Psychosomatic Research-Revised Semi-Structured Interview (DCPR-R SSI), and the Psychosomatic Symptom Scale (PSSS) were used. Clinical characteristics, including glycated hemoglobin (HbA1c) and high-density lipoprotein (HDL), were tested. Flow network analyses were applied to psychosomatic symptoms. Then, a predictability network of psychosomatic symptoms, demographics, and clinical characteristics was constructed.

Results
Compared to healthy controls, the type 2 diabetes networks showed significantly stronger edge connections (global strength type 2 diabetes/healthy controls = 3.56/2.23, p &lt;0.001), especially between PSSS somatic factor and persistent somatization (edge weight difference = 0.29, p &lt;0.001), allostatic overload, and demoralization (edge weight difference = 0.32, p &lt;0.001). The comprehensive network showed high predictability in work (62.5%), sex (43.8%), age (37.8%), diabetes duration (13%), HDL (11.4%), and HbA1c (7.6%), in addition to psychosomatic manifestations.

Discussion and Conclusion
This study not only provides a novel framework for understanding the psychosomatic symptoms specific to type 2 diabetes but also offers robust evidence for targeted interventions for these complex symptoms.
GENOME-WIDE ASSOCIATION STUDY IMPLICATES LIPID PATHWAY DYSFUNCTION IN ANTIPSYCHOTIC INDUCED WEIGHT GAIN: MULTI- ANCESTRY VALIDATION
Authors: Liao *Yundan , Hao Yu , Yue Weihua 
Published: February 2025

Abstract

Background
Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to type 2 diabetes (T2D) and coronary heart disease.

Aims & Objectives
The aim of this study is to identify genetic predictors and expand the unclear genetic mechanism underlying AIWG.

Method
A two-stage genome-wide association study and polygenic risk score (PRS) profiling for AIWG were conducted with three randomized trials, including a discovery cohort of 1,936 schizophrenia patients, a validated cohort of 534 schizophrenia patients, and an external validation of 630 schizophrenia patients from the CATIE study. We applied Mendelian randomization (MR) to investigate the relationship between AIWG and antipsychotic-induced lipid changes (AILCs). A prediction model for AIWG was developed by combining PRS, AILC, and clinical predictors.

Results
Our results identified novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P=1.373×10-9) and rs3824417 in PTPRD (P=3.348×10-9). The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. PRSs for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P=7.58×10−4) and triglycerides (P=2.06×10−3) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating PRSs, AILCs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC=0.79, R2=0.332).

Discussion & Conclusion
Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia.
SINGLE-CELL ANALYSIS IDENTIFIED CELL-TYPE-SPECIFIC AND CONVERGED PATHWAYS OF AUTISM SPECTRUM DISORDER
Authors: Nomura *Jun , Takumi Toru 
Published: February 2025

Abstract

Patients with psychiatric disorders such as autism spectrum disorder (ASD) showed various and heterogeneous clinical symptoms even share the same mutation. Furthermore, the comorbidity of psychiatric disorders makes it more complicated, despite of clinical manifestations of ASD that have been established. In genetic and genomic aspects, ASD has been categorized as a genetic disorder due to studies investigating concordant and discordant monozygotic twins. These past genetic studies have also identified chromosome mutations such as deletion and duplication larger than 1 kb in patients with ASD. These chromosome abnormalities named copy number variations (CNVs) are one of the risk factors associated with ASD. Here, we applied single-cell RNA sequencing (scRNA-seq) to identify CNV- and cell- type-specific abnormalities in ASD by using differentiated neurons from genetically edited mouse embryonic stem (ES) cells. Each mutant cell line used in this study has a psychiatric disorder associated CNV such as 1q21 duplication, 2p16.3 deletion, 3q29 deletion, 7q11.23 duplication, 15q11 deletion, 15q13.3 deletion, 16p11.2 deletion, 16p13.2 deletion, 17p11.2 deletion, 17q12 deletion, Xq27 (Fmr1) deletion, and Xq28 (Mecp2) deletion. Uniform Manifold Approximation and Projection (UMAP), the mathematical manifold learning technique for dimension reduction, identified 16 cell types such as glutamatergic and GABAergic neurons, neural stem cells, microglia, oligodendrocyte precursor cells, and endothelial cells. These cell types were annotated according to cell-type markers. Overall, network analysis based on the differentially expressed gene (DEGs) identified enriched terms such as “splicing”, “neural system”, “axon guidance”, “mitochondria”, and “translation”. Interestingly, “immune system” was also a significant term in these CNVs. We also found a unique association between “endoplasmic reticulum stress signaling” and “GABAergic neurons”, as well as “p53 signaling” and “microglia” respectively in pathway analysis. Surprisingly, “p53 signaling” was preferentially affected by “microglial cluster” regardless of CNV type. Lastly, we focused on “translation machinery” because previous studies have highlighted this biological process as a converged pathway of ASD. Through our transcriptome analysis, we also identified “translation” as a commonly dysregulated pathway regardless of CNV- and cell types. In particular, the mTORC1 complex which includes mTOR is affected in neurons.
In conclusion, our comprehensive transcriptome analysis in single-cell resolution emphasizes not only molecules, and networks, but also converged pathways of ASD which may contribute to the drug development of ASD.

References
Nomura, J. et al. (2022) Autism in a dish: Es cell models of autism with copy number variations reveal cell-type-specific vulnerability [Preprint]. doi:10.1101/2022.02.02.478766.