bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction
Authors: McGeough Kevin M
Published: February 2025

The book begins with an autoethnographical account of the author’s first experiences thinking about the Ark after seeing Raiders of the Lost Ark and how that mirrors many others’ first encounters with it. The chapter argues that the Ark is something of greater interest to nonspecialists than to biblical scholars. Because it is described so vividly in the Bible, it is easy to imagine what the Ark would have looked like. Yet what the Ark “did” is somewhat ambiguous, and that ambiguity has left much room for interpretation. Different communities have been able to imagine their own “Arks,” and while what they have imagined the Ark to look like is consistent among interpretive communities, what the Ark “means” has varied dramatically. The Ark has become a metasymbol with variant meanings, but it bears connotations of antiquity, divinity, and power.
Rethinking the Ark without the Temple
Authors: McGeough Kevin M
Published: February 2025

Chapter 3 examines what the Ark came to mean in Judaism and Christianity in the postbiblical era. It starts by discussing how the Ark continued to be a meaningful symbol in Judaism after the destruction of the Temple in Jerusalem. It debates the possibility that the Torah Ark in synagogues explicitly emerged in synagogue architecture in reference to the Ark. The second half of the chapter focuses on early Jewish and Christian writers, exploring how the Ark was understood in the new theological and philosophical systems of the first few centuries of the Common Era. Also discussed in this chapter are the different theories these ancient writers offer on what happened to the Ark.
Toys and Teaching Tools
Authors: McGeough Kevin M
Published: February 2025

Chapter 7 discusses contemporary material engagements with the Ark: how people interact with models of the Ark, as toys, as travel souvenirs, as recreated objects in museums, and in contemporary Evangelical church experiences. The theoretical theme of this chapter is how people make sense of the Ark, the past, and their world, through engagement with objects. Building off of anthropological models such as “thing theory,” how different communities use various kinds of models of the Ark for communication, education, identity formation, religious experience, and play are explored here. The chapter especially concentrates on film fandom cultures, tourism, and new religious movements.
The Romance of Solomon and Sheba
Authors: McGeough Kevin M
Published: February 2025

The Ethiopian Christian tradition that the Ark has been held in a chapel in Aksum (Our Lady Mary of Zion) for the past three thousand years is the subject of this chapter. It discusses the history of Christianity in Ethiopia, as well as the history of this particular church (contextualizing it within Ethiopian religious traditions). It examines the Kebra Nagast, the Ethiopian account of a dalliance between King Solomon and the Queen of Sheba, which led to her bearing his child, who later became the king of Ethiopia. This son, Menelik, according to the tradition, traveled to Israel to meet his father and returned to Ethiopia with the Ark of the Covenant, where it has been said to reside ever since. The chapter contextualizes this tradition within the context of Ethiopian religion and the dynastic politics that make claims to biblical lineages meaningful. It ends with a discussion of issues surrounding repatriation.
Bibliographic Essay
Authors: McGeough Kevin M
Published: February 2025

The book includes a bibliographic essay, organized according to each chapter of the book. The essay provides information about sources used directly in each chapter and also suggests avenues for further reading. It is aimed primarily at student researchers or for those academics who wish to begin studies of subjects outside of their direct field of interest. The discussion of the individual sources indicates the technical background needed to work with some of them and provides suggestions for introductory-level readings. The essays also offer further background on the history of scholarship beyond the comments made in the body of the book.
The Bird in Glee: On the Nonsemantic
Authors: Stewart Susan
Published: February 2025

This chapter takes up various accounts of nature from philosophers from ancient Greece to the twentieth century. The process philosophy of Alfred North Whitehead, with its concept of nature as event, serves as an important paradigm for thinking about poetry as an art form straining toward that which cannot be perceived, that which is intuited and not merely reasoned. Stewart explores poetic engagement with birdsong to consider the ways in which poets explore the nonsemantic, the rhythmic, and even the meaningless as ways of approaching that which cannot be cognized. The use of nonsense and macaronic verse in traditional English refrains reveals some surprising connections between human language and the language learning of other species.
Behavioural changes in frontotemporal dementia and their cognitive and neuroanatomical correlates
Authors: Rouse Matthew A , Husain Masud , Garrard Peter , Patterson Karalyn , Rowe James B , Lambon Ralph Matthew A
Published: February 2025

Behavioural changes are a central feature of frontotemporal dementia (FTD); they occur in both behavioural-variant (bvFTD) and semantic dementia (SD)/semantic-variant primary progressive aphasia subtypes. In this study, we addressed two current clinical knowledge gaps; (i) are there qualitative or clear distinctions between behavioural profiles in bvFTD and SD, and (ii) what are the precise roles of the prefrontal cortex and anterior temporal lobes in supporting social behaviour? Resolving these conundrums is crucial for improving diagnostic accuracy and for the development of targeted interventions to treat challenging behaviours in FTD. Informant questionnaires to assess behavioural changes included the Cambridge Behavioural Inventory-Revised and two targeted measures of apathy and impulsivity. Participants completed a detailed neuropsychological battery to permit investigation of the relationship between cognitive status (including social-semantic knowledge, general semantic knowledge and executive function) with behaviour change in FTD. To explore changes in regional grey matter volume, a subset of patients had structural MRI. Diagnosis-based group comparisons were supplemented by a transdiagnostic approach which encompassed the spectrum of bvFTD, SD and “mixed” or intermediate cases. Such an approach is sensitive to the systematic graded variation in FTD and allows the neurobiological underpinnings of behaviour change to be explored across an FTD spectrum. We found a wide range of behavioural changes across FTD. Although quantitatively more severe on average in bvFTD, as expected, the item-level analyses found no evidence for qualitative differences in behavioural profiles or “behavioural double dissociations” between bvFTD and SD. Comparisons of self and informant ratings revealed strong discrepancies in the perspective of the caregiver versus patient. Logistic regression revealed that neuropsychological measures had better discriminative accuracy for bvFTD versus SD than caregiver-reported behavioural measures. A principal component analysis of all informant questionnaire domains extracted three components, interpreted as reflecting: (1) apathy, (2) challenging behaviours and (3) activities of daily living. More severe apathy in both FTD subtypes was associated with (a) increased levels of impaired executive function and (b) anterior cingulate cortex atrophy. Questionnaire ratings of impaired behaviour did not correlate with either anterior temporal lobe atrophy or degraded social-semantic knowledge. Together, these findings highlight the presence of a wide range of behavioural changes in both bvFTD and SD, which vary by degree rather than quality. We recommend a transdiagnostic approach for future studies of the neuropsychological and neuroanatomical underpinnings of behavioural deficits in FTD.
Retinal microstructure and microvasculature in association with brain amyloid burden
Authors: Egle Marco , Hamedani Ali G , Deal Jennifer A , Ramulu Pradeep Y , Walker Keenan A , Wong Dean F , Sharett A Richey , Abraham Alison G , Gottesman Rebecca F
Published: February 2025

Cortical amyloid burden is associated with neuronal and vascular abnormalities. The retina shares significant structural and physiological similarities with the brain. This study assessed the association of retinal microstructural and microvascular signs with cortical amyloid burden in the prospective Atherosclerosis Risk in Communities-Positron Emission Tomography study. One hundred and twenty-four participants without a diagnosis of dementia underwent florbetapir PET (2011–13) and optical coherence tomography and optical coherence tomography angiography imaging (2017–19). Retinal nerve fibre thickness, total macular thickness and the ganglion cell-inner plexiform layer thickness were derived from the optical coherence tomography scan. Vessel density and the foveal avascular zone were measured on the 3 × 3 mm2 optical coherence tomography angiography scan. Amyloid burden, defined by global cortical standardized uptake value ratio, was treated as a dichotomous (standardized uptake value ratio > 1.2) and continuous outcome measure in logistic and robust linear regression models, respectively. Only lower intermediate capillary plexus vessel density [β (95% confidence interval) = −0.05 (−0.12, −0.01)] was significantly associated with increased continuous amyloid standardized uptake value ratio but not elevated dichotomous amyloid burden independently of demographic, genetic and vascular risk factors. No other retinal measure showed a significant association. Microvascular signs may accompany greater amyloid burden in late life in individuals without dementia.
The effect of the ‘Every Mind Matters’ campaign on mental health literacy: the moderating roles of socioeconomic status and ethnicity
Authors: Ronaldson Amy , Chua Kia-Chong , Hahn Jane , Henderson Claire
Published: February 2025

We previously reported short-lived improvements in mental health literacy following the Every Mind Matters campaign, followed by a return to baseline levels. In this study, we aimed to examine whether either socioeconomic status or ethnicity moderated these improvements. We conducted regression analyses on a nationally representative, repeated cross-sectional dataset of nine survey waves from September 2019 to March 2022. Interaction terms (ethnicity*wave, socioeconomic status*wave) were entered into regression models to assess the moderating effect of these variables. Where significant interactions emerged, we obtained marginal estimates and plotted them for ease of interpretation. We found no evidence that improvements seen in mental health literacy following the launch of Every Mind Matters were moderated by ethnicity or socioeconomic status. Over time, there was some evidence of lower scores relating to symptoms recognition, knowledge of actions to improve mental health, and desire for social distance (stigma) among adults of lower socioeconomic status, which converged again for symptom recognition. These findings suggest that while a web resource can empower people and improve mental health literacy, in relation to ethnicity and socioeconomic status, it may be that while this can avoid a widening of inequalities it is insufficient to lead to a narrowing of them.
COMPARING IMMUNOCYTOKINES LEVELS BETWEEN ALCOHOL- DEPENDENT PATIENTS WITH AND WITHOUT DELIRIUM TREMENS
Authors: Hsu *Shu Hao , Kao Chung-Feng , Chang Hu-Ming , Huang Ming-Chyi
Published: February 2025

Background

Alcohol is a significant modulator of the immunocytokine system. Alcohol dependence (AD) can lead to a range of psychological and physical problems. Alcohol withdrawal syndrome (AWS) is a hallmark of AD and can manifest in various clinical phenotypes, including delirium tremens (DTs), which is considered the most severe and distinct form of AWS. Previous evidences suggest that AD is associated with dysregulation of immunocytokines such as Interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), and tumor necrosis factor-alpha (TNF-α). However, whether there is a difference between patients with and without DTs was not known.

Aims & Objectives

This study aimed to investigate differences in IL-6, sIL-6R, and TNF-α levels between patients with AD who did and did not develop DTs.

Method

We enrolled 85 inpatients diagnosed with AD based on DSM-IV criteria and 49 health control (HC) participants. Among AD groups, 35 participants experienced DTs (classified as DTs group). Blood samples were collected from the AD group on the first and seventh days of withdrawal, as well as from the HC group. Serum levels of IL-6, sIL-6R, and TNF-α were measured using enzyme-linked immunosorbent assays.

Results

Patients with AD exhibited significantly elevated TNF-α levels and reduced sIL-6R levels at baseline compared to HCs. No significant differences in TNF-α and sIL-6R levels were observed between DTs and non-DTs groups. Moreover, the DTs group had the highest IL-6 levels, followed by the non-DTs group, then the HC group. After one week of alcohol withdrawal treatment, sIL-6R levels were normalized and comparable for the DTs and non-DTs groups. The levels of TNF-α remained elevated in the DTs group; however, the non-DTs group exhibited a significant decrease in TNF-α level. Additionally, IL-6 levels decreased significantly in the DTs group, while they remained unchanged in the non-DT group.

Discussion & Conclusion

Our findings suggest immunocytokines dysregulation may be associated with the pathophysiology of AD. The difference of IL-6 and TNF-α levels between DT and non-DT groups supports the potential role of immunocytokines in discriminating AD subgroups and highlights the potential clinical utility as a marker for DTs. Current evidence also suggests that convergent immune pathways may be involved in AUD and in these comorbid disorders.
ACTIVITIES OF OREXIN NEURONS IN MOTIVATIVE BEHAVIOR
Authors: Mizoguchi *Hiroyuki , Dong Yutao , Yamanaka Akihiro , Yamada Kiyofumi
Published: February 2025

Background

Orexin neurons regulate physiological functions, including not only energy homeostasis and wakefulness, but also motivated behaviors.

Aims & Objectives

Here, we examined the roles of orexin neurons in motivated behaviors. [Method] We measured the activities of orexin neurons using fiber photometry under a free-moving condition, in which the rats were subjected to the fixed ratio (FR) or progressive ratio (PR) schedule of a touchscreen-based automated operant task.

Results

We found that breakpoint in PR test was increased when orexin neurons were activated by using chemogenetic approach, while the breakpoint was reduced when orexin neurons were disrupted by diphtheria toxin A. We also found that under FR5 conditions in which rats were able to obtain a food pellet by touching the screen consecutively five times, the activity in orexin neurons was increased after the fifth screen touch (after which one food pellet is delivered). The activity peaked before rats obtained reward, and then decreased after food intake. Next, we measured orexin neurons activities under FR20 which seems to be more difficult for rats to obtain rewards, compared with those under FR5. Under FR20 conditions, the orexin activities were higher than those in FR5 conditions. In the PR schedule test, the orexin activities were also gradually increased.

Discussion & Conclusion

These observations suggest that the orexin activities are associated with motivational behaviors, and that dynamic changes in activation of orexin neurons may be involved in craving and reward prediction, and satisfaction.
PLASMA PHOSPHOETHANOLAMINE LEVELS AS A BIOMARKER FOR MONITORING MAJOR DEPRESSIVE DISORDER
Authors: Kawamura *Noriyuki , Nakata Akinori , Harada Tsuyoto , Ohashi Yoshiaki , Sato Hajime , Sasaki Kazunori , Higuchi Teruhiko
Published: February 2025

Background

We have reported that plasma phosphoethanolamine (PEA) concentration is a candidate biomarker of depressive disorder (1).

Aims & Objectives

To characterize this marker and investigate its clinical usefulness, we carried out an observational study while respecting the subjects' freedom to participate in the study.

Method

Psychiatric assessments were made with the Structured Clinical Interview for DSM-5. The absolute concentrations of PEA in the samples from a psychiatric primary care clinic were measured at Human Metabolome Technologies to characterize its ability as MDD biomarker between 2011 and 2020.

Results

Here we show that 295 had depressive disorders, 264 had psychiatric disorders other than depression, and 17 had physical disorders without psychiatric disorders out of the 576 Japanese patients. In 170 patients with MDD only, in whom remission was easily identified, plasma PEA levels were measured at two or more time points. These levels dropped significantly in depressive episodes, increased as remission approached and were significantly higher in remission.Psychiatric diagnosis alone explained 38% of the variance in plasma PEA concentrations. Receiver operating characteristic (ROC) curve analysis also showed sufficient discriminatory power to detect depression, with an area under the curve (AUC) of 0.84 (95% confidence interval (CI): 0.80-0.87).

Discussion & Conclusion

ConclusionsOur study suggests that plasma PEA concentration is a promising candidate monitoring biomarker for major depressive disorder (MDD) with strong diagnostic ability. Further studies are needed.

References

(1)Kawamura,N. Shinoda,K. Sato,H. Sasaki,K. Suzuki,M. Yamaki,K. Fujimori,T. Yamamoto,H., Osei-Hyiaman,D. and Ohashi,Y. (2018) 'Plasma metabolome analysis of patients with major depressive disorder.’ Psychiatry and Clinical Neuroscience, 72(5), pp. 349-361
EFFECTS OF CHRONIC METHAMPHETAMINE ADMINISTRATION ON RESTING-STATE FUNCTIONAL CONNECTIVITY IN CYNOMOLGUS MONKEYS
Authors: Chun *Jiwon , Jin Yeung Bae , Lee Sang-Rae , Kim Dai Jin
Published: February 2025

Background

Maladaptive decision-making by methamphetamine users may reflect circuit-level dysfunction underlying deficits in neural activity. In a previous study, it was reported that heightened resting-state connectivity within the mesocorticolimbic system, coupled with reduced prefrontal cortical connectivity, created a bias toward reward-driven behavior over cognitive control in methamphetamine users.

Aim & Objectives

The primary aim of this study was to investigate the effect of chronic methamphetamine administration on resting-state functional connectivity in cynomolgus monkeys. Additionally, the study sought to elucidate the effect of chronic methamphetamine administration based on varying drug administration periods.

Method

Chronic Drug Exposure: The MA group was administered 0.9% saline for the initial 4 weeks followed by MA for the subsequent 7 weeks (5-8 weeks at doses of 0.1-0.75mg/kg; and 9-11 weeks at a dose of 0.75mg/kg).

MRI Procedure

On the MRI scanning day, anesthesia was induced using atropine, ipratropium, and ketamine hydrochloride injections. After oral intubation, anesthesia was maintained with 1.5% isoflurane mixed with oxygen. Monkeys were seated in a custom-built primate chair with a head-fixation system and custom RF coil, then placed in the MRI bore for imaging. The isoflurane level was reduced to 1% during the imaging procedure.

Imaging Protocol

MA monkeys underwent resting-state fMRI at 5 time points (baseline, 4, 5, 7, 9, 11 weeks) and four healthy control (HC) monkeys at baseline, 5, and 11 weeks. Seed-based correlation analysis was employed to produce functional connectivity maps with the nucleus accumbens as ROIs. Voxel-wise tests were conducted using the GLM in SPM12 to study RSFC changes over MA administration duration and intergroup differences.

Image Processing

Performed in SPM12, where rsfMRI data were realigned, coregistered with structural T1 data, spatially normalized, and smoothed. Other processes included motion correction, global signal normalization, and band pass filtering.

Results

Altered functional connectivity was observed between the striatum and medial prefrontal cortex in the monkey with chronic exposure to MA.

Discussion & Conclusion

The alterations in functional connectivity observed in the monkey striatum due to chronic MA exposure provide valuable insights into the neural mechanisms that could underlie behavioral abnormalities and drug dependence resulting from long-term MA exposure.
EFFECTS ON THE THALAMUS AND INSULAR CORTEX DURING VOCAL EMOTION PROCESSING BY MODAFINIL AND BUPROPION: A PHARMACOLOGICAL MRI STUDY
Authors: Koeda *Michihiko , Hama Tomoko , Ikeda Yumiko , Suzuki Hidenori , Okubo Yoshiro , Tateno Amane
Published: February 2025

Background

It is known that Modafinil is the medicine to treat Narcolepsy and Attention Deficit Hyperactivity Disorder (ADHD), whereas as a side effect, modafinil is known to react emotional instability and suicidal ideation (Vorspan 2005). Bupropion is used as antidepressant to improve the recognition of negative feelings. These two medicines could affect to cerebral activation of emotional processing. Recent our studies have demonstrated that compared with placebo, modafinil decreased right thalamus activation in the recognition of vocal affective processing, and bupropion increased cerebral activation in the insular and superior temporal gyrus (Hama et.al 2021a, 2021b). However, to our knowledge, no study has not been directly examined these pharamacological effects to emotional brain circuit among the placebo, modafinil and bupropion.

Purpose

In the present study, we aimed to investigate the effect of modafinil and bupropion on thalamus-insular activation while the subjects were recognizing vocal affective processing, compared with placebo by using a functional MRI. Methods: Sixteen healthy volunteers (male 8) participated in this study. Before the experiments, all participants agreed with the protocol approved by ethics committee. Three series of fMRI scans, using either placebo, modafinil (200mg), or bupropion (150 mg), were examined. Each subject took a medicine before 2 hours of fMRI scanning. An auditory emotional valence judgement task was performed during fMRI scanning. The acute effects of modafinil and bupropion on cerebral activation in the emotional circuit and behavioral performance during emotional processing were analyzed by using SPM analysis, 3×4 full factorial design. Three drugs (placebo, modafinil, and bupropion) effects and 4 emotions (neutral happy, sad, anger) effects were investigated.

Results

Main effect of drug was significantly observed at the left insular and the right thalamus (FWE p<0.05). In the left insular, compared with placebo, cerebral activation by bupropion was significantly greater, whereas that by modafinil was slightly greater. In the right thalamus, compared with placebo, cerebral activation by modafinil was significantly less, that by bupropion was slightly less. Further, interaction effect between drug and emotion was significantly observed at the posterior cingulate (FWE p<0.05).

Discussion and Conclusions

From these findings, we confirmed that both modafinil and bupropion affect function of the insular and thalamus in the recognition of the emotion. Especially, modafinil significantly decrease cerebral activation at the right thalamus, bupropion significantly increase cerebral activation at the left insular.
MORE PRONOUNCED NEUROAXONAL INTEGRITY DISTURBANCES IN METHAMPHETAMINE-ASSOCIATED PERSISTENT PSYCHOSIS COMPARED TO SCHIZOPHRENIA
Authors: Huang *Ming-Chyi , Liu Tung-Hsia , Liu Yu-Li
Published: February 2025

Background

Methamphetamine (METH) can cause multiple physical and psychological harms. Psychosis is one of the most serious health consequences from using METH, with this requiring aggressive treatment and being associated neurocognitive impairment and structural brain abnormalities. While the majority of METH-associated psychosis are brief (METH-associated brief psychosis, MBP); the psychosis can become persistent for >1 month in a subset of people (METH-associated persistent psychosis, MPP), with a symptom profile substantially similar to schizophrenia. Blood levels of neurofilament light chain (NFL) have been proposed as a measure of neuroaxonal integrity in several neuropsychiatric disorders.

Aims & Objectives

We aimed to delineate the neuroaxonal damage linked to METH-associated psychosis, especially its persistent form, and compare it to schizophrenia.

Methods

We enrolled 135 individuals with METH use disorder (55 with no psychosis [MNP group], 54 with MBP, and 24 with MPP), 78 with schizophrenia, and 85 healthy controls. Blood NFL levels measured by single molecule array (SiMoA) immunoassay. We compared NFL levels between different groups and used regression analyses to identify clinical variables related to NFL levels.

Results

Individuals with MUD had significantly higher NFL levels compared to controls but comparable to patients with schizophrenia. We found age (p<.01) and duration of METH use (p = 0.01) were positively correlated with NFL levels whereas BMI is negatively correlated with NFL levels. Subsequent group comparisons showed that the NFL levels in MPP group were higher than MBP and MNP group while the levels were comparable between the latter two groups. Interestingly, MPP group had increased NFL levels compared to schizophrenia group. Furthermore, those with a prolonged psychosis associated with METH, i.e. schizophrenia-like, had a even higher NFL levels than all the resting groups.

Discussion & Conclusions

These results suggest substantial neuroaxonal alterations following METH use, with a longer duration associated with higher injury. In particular, persistent psychosis The pronounced increase of NFL levels in the people with MPP and suffering from persistent psychosis might indicate that dual disruptive effect (from METH use and psychosis) on the neuroaxonal integrity and the pathology could differentiate MPP and schizophrenia.
ESTIMATING A PROBABILITY OF REDUCING RISKS ASSOCIATED WITH SMOKING CONVENTIONAL CIGARETTES USING THE THS2.2 (IQOS) TECHNOLOGY
Authors: Sergazy *Shynggys , Gulyayev Alexander , Shulgau Zarina , Nurgozhin Talgat
Published: February 2025

Objective

The aim of the current review was the collection and analysis of information about the tobacco heating system THS commercialized as IQOSTM technology in comparison with conventional cigarettes CC.

Data Sources

The collection of data was performed with the help with the Pubmed database and other relevant sources including the websites of official health regulating bodies e.g. FDA, WHO, Public Health England for articles published until 15 February 2018 that contained key phrases as IQOS, tobacco heating systems THS, heat-not-burn, and other sources which were found to be relevant to the topic.

Data Extraction

Two reviewers defined independently the relevance of the articles and extracted the information from the literature sources.

Data Synthesis

In the review, there were included articles and other sources where the following characteristics of IQOS THS2.2 were described: chemical composition of the aerosol, studies conducted in vitro and in vivo, as well as clinical studies, and other relevant information such as potential THS aerosol carcinogenic properties, awareness, comments by critics, and others. By the results of the available information, THS aerosol is much less toxic comparing with CC smoke and can significantly reduce the harm and risk of development of tobacco-related diseases for smokers. However, it is advised to conduct the experiments with the expanded list of Harmful and Potentially Harmful Constituents HPHC from the FDA list. There is also a need in clinical research of a longer period with the racial diversity of subjects where the biomarkers corresponding to various tobacco disease conditions could be studied.

Conclusion

The use of THS technology could lead to significant harm reduction and a reduction in the risk of tobacco-related diseases. However, it still poses a risk and cannot be recognized as completely safe.
ROLE OF L-LACTATE AND AMP-ACTIVATED PROTEIN KINASE IN ENHANCED FEAR MEMORY IN DIABETIC MICE
Authors: Ikeda *Hiroko , Yamagishi Aimi , Yonemochi Naomi
Published: February 2025

Aim & Objectives

The prevalence of mental disorder including depression and anxiety is higher in patients with diabetes mellitus than in the general population, but it is unclear how diabetes mellitus causes mental disorder. Because several studies suggest that hyperglycemia affects brain function, the present study investigated the role of L-lactate, which is produced from glucose in the brain, in enhanced fear memory in diabetic mice. In addition, it has been reported that L-lactate inhibits AMP- activated protein kinase (AMPK). Thus, we also examined whether AMPK in the brain is involved in enhanced fear memory in diabetic mice.

Method

Male ICR mice were used. Diabetes was induced by streptozotocin, with experiments conducted 2 weeks after streptozotocin injection. Fear memory was measured by the conditioned fear test. Protein levels of AMP-activated protein kinase (AMPK) and phosphorylated AMPK in the amygdala and hippocampus, which are thought to be involved in fear memory, were measured by Western blot.

Results

Diabetic mice showed a longer duration of freezing than control mice. In diabetic mice, L-lactate level was increased in the amygdala and hippocampus. I.c.v. injection of L-lactate into non-diabetic mice increased duration of freezing. In addition, i.c.v. injection of L-lactate into non-diabetic mice significantly decreased the protein level of phosphorylated AMPK, which is an active form of AMPK, in the hippocampus. Increase in duration of freezing induced by L-lactate was inhibited by the AMPK activator AICAR. The protein level of phosphorylated AMPK was decreased in the amygdala and hippocampus of diabetic mice. I.c.v. injection of AMPK inhibitor compound C into non-diabetic mice increased duration of freezing, whereas i.c.v. injection of AICAR inhibited the increased duration of freezing in diabetic mice. Finally, the AMPA receptor antagonist NBQX inhibited the increased duration of freezing following i.c.v. injection of L-lactate or compound C and the same injection also inhibited the increased duration of freezing in diabetic mice.

Discussion & Conclusion

Our results indicate that fear memory is enhanced in diabetic mice. In addition, it appears that increase in L-lactate production, possibly from plasma glucose in the amygdala and hippocampus, plays a key role in enhanced fear memory in diabetic mice. Moreover, increase in L-lactate in the amygdala and hippocampus inhibits AMPK activity, which enhances fear memory in diabetic mice possibly through activation of glutamate neurons and/or AMPA receptor function.
CELLULOSE RICH FOOD INDUCES INTESTINAL DISTURBANCE THAT LEADS ANXIETY-LIKE BEHAVIOR AND AMYGDALAR DOPAMINERGIC HYPERACTIVITY
Authors: Nozaki *Chihiro , Ito Kaede , Shibata Shigenobu
Published: February 2025

Background

It is indicated the intestinal environment affects anxiety and emotions directly in recent years. For example, improvement of intestinal environment is known to suppresses the anxiety-like behavior in mice model of depression and schizophrenia. Such gut-brain relationships, called “gut-brain axis”, are suggested to involve both endocrine and neuronal system via the vagus nerve. However, previous studies have mainly used psychiatric disease models, therefore how intestinal environment will affect on emotion in normal animals remains unclear.

Aims & Objectives

In the present study, we evaluated the psychological and physiological effect of food-induced intestinal environment modification.

Method

We divided 7-weeks-old male ICR mice into two groups, and fed either MF (Standard diet: contains various dietary fibers) or AIN-93M (contains cellulose alone) for 8 or 16 weeks. Behavioral test (marble burying test) as well as measurement of peristalsis, cecum short-chain fatty acid (SCFA) and monoamine level of various brain region has been determined in these animals.

Results

Either 8-weeks or 16-weeks exposure of AIN-93M reduced peristalsis and cecum SCFA, while increased intestinal inflammation, suggesting the exacerbation of intestinal environment in these animals comparing to MF-fed control group. Interestingly, AIN-93M-fed animals also displayed the significant increase of marble-burying behavior compared to MF-fed group, indicating the enhancement of anxiety by that 16-week exposure to AIN-93M. These effects were abolished by vagotomy, suggesting that enhanced anxiety is caused by the AIN-93M-induced intestinal disturbance through gut-brain axis. We also found the dopamine level in amygdala was significantly increased in the AIN-93M-fed group.

Discussion & Conclusion

These results suggest that the cellulose-induced intestinal disturbance and decreased intestinal function caused overactivation of dopaminergic system, which may enhance the anxiety level. Also as vagus nerve is critical to the anxiety observed in cellulose-fed animals, we propose that exacerbation of gut environment may directly cause the mental illness or psychiatric disorder through gut-brain axis.
ASSOCIATION BETWEEN MENTAL DISORDERS AND MORTALITY AMONG PATIENTS WITH COVID-19 IN SOUTH KOREA
Authors: Park *Subin
Published: February 2025

Background

This study investigated the association between mental disorder and mortality risk of those with COVID-19 patients. Specifically, the mortality risk of patients who were first diagnosed with mental disorders during the COVID-19 pandmic was considered.

Methods

The population-based cohort data from the National Health Insurance Service-COVID-19 database from Oct 2020 to Dec 2021 was utilized. The total patients were divided into three groups: 1) without mental disorder, 2) pre-existing mental disorder (i.e., History), and 3) first diagnosed with mental disorder during the COVID-19 pandmic (i.e., Pandemic onset). The primary outcome was all cause of mortality. Multivariable linear regression analysis was used to adjust for possible confounders.

Results

We included confirmed COVID-19 patients in the analysis (n=433,822). There were 352,473 patients (81.25%) without mental disorder group, 54,854 patients (12.64%) in the History group, and 26,495 patients (6.11%) in the Pandemic onset group. Overall, the all cuase of mortality rate was 0.71% (n=3,085). Compared to without mental disorder group, the History group was (AOR=1.42, 95% CI=1.30- 1.55) and Pandemic onset group (AOR=1.82, 95% CI=1.63-2.04) had a higher risk of mortality.

Discussion and Conclusion

We found that patients with mental disorders had a higher risk of mortality compared to those without mental disorders among patients with COVID-19. In particular, mortality is higher for patients who were first diagnosed with mental disorders during the COVID-19 pandemic.
THE IMPACT OF CHILDHOOD TRAUMAS ON RESPONSE TO ACCELERATED RTMS IN TREATMENT-RESISTANT DEPRESSION
Authors: D'andrea *Giacomo , Pettorruso Mauro , Mancusi Gianluca , Cavallotto Clara , Carullo Rosalba , Mosca Alessio , Carlo Francesco Di , Chiappini Stefania , Martinotti Giovanni
Published: February 2025

Background

Childhood traumas have long been recognized as pivotal determinants in the progression and severity of depressive disorders, especially in treatment-resistant depression (TRD). These early life adversities can induce distinct neurostructural and functional alterations, potentially mediating the responsiveness to antidepressant therapies.

Aims & Objectives

To evaluate the interplay between childhood traumas and treatment outcomes in TRD patients undergoing an accelerated repetitive transcranial magnetic stimulation (arTMS) regimen.

Methods

In this multicentric, prospective analysis, we enrolled 51 TRD patients (average age 56±13.305; M/F=28/23) involved in an intensive arTMS protocol— comprising 4 daily sessions over 5 consecutive days, targeting the Left Dorsolateral Prefrontal Cortex at High Frequency/10 Hz. Comprehensive psychiatric evaluations were performed, employing the MADRS scale to chronicle depressive symptoms at various stages (baseline/T0, one week/T1, and a month/T2 post-treatment) and the CTQ scale (at T0) to quantify exposure to traumas during early life. CTQ scores guided the bifurcation of patients into two cohorts: those minimally exposed to childhood traumas (Low_Trauma) and their highly exposed counterparts (High_Trauma). We developed a General Linear Model (GLM), implementing repeated measures ANOVA (rm-ANOVA), to discern the interplay between temporal shifts (T0vsT1vsT2) and trauma exposure groups.

Results

Our rm-ANOVA underscored a marked improvement in MADRS scores from T0 through T1 to T2 (F98,2=73.938; P<0.001), attesting the robust efficacy of the arTMS modality. Intriguingly, there emerged a pronounced interaction between the temporal trajectory and trauma exposure groups (Low_trauma vs. High_Trauma) (F98,2=5.980; P=0.004). Subsequent analyses elucidated a more pronounced symptom amelioration in the Low_Trauma cohort. Notably, the comparative efficacy was markedly elevated in the group with lesser traumatic experiences (Cohen’ s d: 2.164 vs. 1.204), underscoring the potential inhibitory role of extensive childhood trauma on therapeutic outcomes.

Discussion & Conclusions

Early-life traumatic events seemingly interface with distinct neural networks, potentially resistant to modulation by the arTMS protocol. Such profound traumas during formative years could thus emerge as a harbinger of suboptimal treatment outcomes. A deeper exploration into TMS's neurophysiological dynamics and trauma's psychobiological underpinnings might pave the way for a better therapeutic approach, clinically-oriented, for TRD patients.
THE MEDIATING EFFECTS OF WORKING HOURS, SLEEP DURATION, AND DEPRESSIVE MOOD ON THE ASSOCIATION BETWEEN SHIFT WORK AND THE RISK OF SUICIDAL IDEATION IN KOREAN WORKERS
Authors: Park Mina , Ho *Dham , Lim Weon-Jeong
Published: February 2025

Aims & Objectives

This study aimed to investigate the mediation effects of working hours, sleep duration, and depressive mood on the association between shift work and the risk of suicidal ideation in Korean workers.

Method

Data from 33,047 workers were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys conducted in 2007–2018. Healthy workers without depressive disorders and chronic medical illnesses were included in the current study. Shift work patterns, sleep duration, working hours, depressive mood, and suicidal ideation were assessed using self-reported questionnaires. Multivariate logistic regressions were used to examine the association between shift work and the risk of suicidal ideation. Additionally, mediating studies were conducted to identify the roles of working hours and sleep durations on the association.

Results

Compared with daytime workers, shift workers had 1.33 times greater risk of suicidal ideation (OR=1.33, 95% Cl = 1.17-1.52, p <0.001). Specifically, among shift work patterns, fixed-night shift, 24-hours rotating shift and irregular rotating shift was associated with the risk of suicidal ideation than daytime workers (irregular rotating shift: OR= 1.92, 95% Cl = 1.29-2.86, p =0.001; fixed-night shift: OR= 1.75, 95% Cl= 1.32-2.31, p <0.001; 24- hours rotating shift: OR= 1.58, 95% Cl= 1.06-2.36, p= 0.024). In the mediating study, working hours, sleep duration and depressive mood significantly mediated the relationship between shift work and suicidal ideation (direct effect: β=0.019, p=0.001; indirect effect: β=0.004, p=0.031; total effect: β=0.023, p<0.001).

Discussion & Conclusion

This study revealed that shift workers had a greater risk of suicidal ideation. The patterns significantly associated with suicidal ideation were irregular rotating, fixed-night, and 24- h rotating shifts. The pathway analysis revealed serial mediating effects of working hours, sleep duration, and depressive mood on the association between shift work and suicidal ideation.
KNOCKDOWN OF CONNEXIN43 POTENTIATES ANTIDEPRESSANT EFFECT ON BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION IN PRIMARY CULTURED ASTROCYTES
Authors: Tokunaga *Nozomi , Nakamura Yoki , Hisaoka-Nakahsima Kazue , Morioka Norimitsu
Published: February 2025

Background

The number of depression patients is increasing, which is one of the society problems in the world. In general, antidepressants affect through the increase of monoamine concentration at synaptic cleft. Although antidepressants upregulate monoamine level immediately after administration, several months are required for the manifestation of antidepressant effect in patients of depression, suggesting the other mechanism which is independent with monoamine. Moreover, the therapeutic satisfaction is very low because antidepressant drugs are not effective for one-third of patients and the most appropriate drug for each patient is different. Therefore, the development of biomarker to assess the efficacy of antidepressants is needed. Connexin43 (Cx43) is highly expressed in astrocytes, which is the most abundant glia cells in the brain, and contributes to not only intercellular molecular transportation but also intracellular signaling. It is demonstrated that Cx43 expression is reduced in the prefrontal cortex and hippocampus of depressive patients, suggesting that Cx43 may be involved in the pathology of depression. Our previous study showed that Cx43 expression in hippocampus was negatively correlated with the antidepressant effect of amitriptyline in the depressive model mice. In addition, we demonstrated that amitriptyline increases brain-derived neurotrophic factor (BDNF) expression in primary cultured astrocytes. However, the significance of Cx43 reduction for the antidepressant effect and the influence of Cx43 downregulation for BDNF expression by antidepressant drug in the astrocytes are still uncovered.

Aims & Objectives

The current study examined whether amitriptyline potentiates BDNF expression in astrocytes with reduced Cx43 expression, and the mechanism of this potentiation.

Method

Primary cultured astrocytes were prepared from the cerebral cortex of neonatal Wistar rats. The expression of Cx43 was downregulated by RNA interference. The expression of mRNA and protein were measured by real-time PCR and western blotting, respectively.

Results

Downregulation of Cx43 potentiated the amitriptyline-induced BDNF expression in cultured astrocytes. This potentiation was significantly suppressed by the blockade of LPA1/3 receptors, Src tyrosine kinase, and extracellular signal-regulated kinase (ERK).

Discussion & Conclusion

The current study revealed that reduced Cx43 expression potentiates the amitriptyline-induced BDNF expression in cortical astrocytes. In addition, LPA1/3-mediated Src-ERK signaling is crucial in the potentiation of amitriptyline-induced BDNF expression in Cx43-downregulated astrocytes. These results indicate the downregulation of Cx43 observed in the depressive patients might contribute to therapeutic effect of antidepressants.
FACTORS INFLUENCING SUBJECTIVE MEMORY COMPLAINTS AMONG COMMUNITY DWELLING ELDERLY IN URBAN COMMUNITY
Authors: Lee *Kyoung Hwan
Published: February 2025

Background

There are many factors influence subjective memory complaints including neurocognitive disorder, mood disorder and anxiety disorder.

Aims & Objectives

We examined the factors influencing subjective memory complaints among community dwelling elderly in urban area.

Method

The subjects of this research were 160 community-dwelling elderly people without dementia and major depressive disorder. The questionnaires regarding the socio-demographic characteristics were conducted by each person. They include Korean version of Subjective Memory Complaints Questionnaires (SMCQ), Korean version of Short Geriatric Depression Scale (SGDS-K) and Korean version of Mini-Mental State Examination (K-MMSE). Subjective memory complaints were defined as above 4 points of SMCQ.

Results

39.38% of the subjects had subjective memory complaints. There were significant associations between subjective memory complaints and SGDS-K (p<0.001), physical illness (p=0.001), but there was no association with K-MMSE (p=0.383).

Discussion & Conclusion

There is a discrepancy between subjective memory complaints and actual cognitive impairments. This discrepancy suggests that the depressive disorders including minor depressive disorder and subsyndromal depression, might play a role in the subjective memory complaints rather than actual cognitive impairments in community-dwelling elderly people. Therefore, the treatments for the depressive disorders should be considered in dealing with the subjective memory complaints.
AN OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TREATMENT WITH LEMBOREXANT IN SUBJECTS WITH CHRONIC INSOMNIA (SOMNUS STUDY)
Authors: Ozone *Motohiro , Hirota Susumu , Ariyoshi Yu , Hayashida Kenichi , Ikegami Azusa , Habukawa Mitsunari , Ohshima Hayato , Harada Daisuke , Hiejima Hiroshi , Kotorii Nozomu , Murotani Kenta , Taninaga Takehiro , Uchimura Naohisa
Published: February 2025

Background

Effective alternative therapies are needed to improve outcomes in the treatment of insomnia disorder due to concerns regarding the risks of tolerance, dependence, falls and withdrawal syndrome with the use of pharmacological treatments such as benzodiazepine-receptor agonists (BZRA). Lemborexant (LEM), a competitive dual orexin-receptor antagonist approved in Japan and other countries to treat adults with insomnia, has shown superior therapeutic efficacy to zolpidem extended-release 6.25 mg in a phase 3 clinical trial; therefore, LEM may be a potential alternative candidate.

Aims & Objectives

To evaluate whether the approach of a direct transition to LEM either from a Z-drug (zolpidem, zopiclone, or eszopiclone) or suvorexant (SUV) monotherapy or from SUV or BZRA and ramelteon (RMT) combination therapy can be supported for patients with insomnia.

Methods

A prospective, nonrandomized, open-label, multicenter study conducted in Japan with 90 subjects with chronic insomnia dissatisfied with current treatment was designed to investigate whether direct transition to LEM improved patient satisfaction. The study was comprised of four cohorts: (1) nonbenzodiazepine sedative-hypnotic (Z-drug) monotherapy, (2) orexin receptor antagonist (SUV) monotherapy, (3) SUV plus BZRA combination therapy, and (4) melatonin receptor agonist (RMT) plus BZRA combination therapy. The primary outcomes were continuation of treatment after 2 weeks (end of titration phase) and 14 weeks (titration phase and maintenance phase), as well as responses on the Patient Global Impression – Insomnia version (PGI-I) and Insomnia Severity Index (ISI) scales. Subjects in the BZRA combination therapy groups could attempt, but were not required, to decrease BZRA use during the maintenance phase. This study was approved by the Certified Clinical Research Review Board, and informed consent was obtained.

Results

In all, 95.6% (n=86/90) successfully transitioned to LEM after 2 weeks, and LEM continuation rates were 97.8% (n=88/90) at the completion of the titration phase and 82.2% (n=74/90) at the completion of the maintenance phases. At 14 weeks, dose reduction and interruption of BZRA occurred in 12.5% (n=4/32) of the combined cohort. In the entire cohort, PGI-I scores showed a greater percentage of positive responses than negative responses. ISI total scores also improved over time after the transition to LEM. The overall incidence of adverse events was 47.8% (n=43/90) and none were serious.

Discussion & Conclusion

These findings suggest that direct transition to LEM is a valid treatment option for insomnia in patients who are dissatisfied with their current treatment.

Support

Eisai, Ltd.