bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortico-hippocampal networks underpin verbal memory encoding in temporal lobe epilepsy
Authors: Fiore Giorgio , Giampiccolo Davide , Xiao Fenglai , Koepp Matthias J , Iglesias Juan E , Vos Sjoerd B , de Tisi Jane , McEvoy Andrew W , Bertani Giulio A , Locatelli Marco , Finn Roisin , Caciagli Lorenzo , Sidhu Meneka , Galovic Marian , Baxendale Sallie , Duncan John S , Miserocchi Anna
Published: February 2025

Knowledge of the structural underpinnings of human verbal memory is scarce. Understanding the human verbal memory network at a finer anatomical scale will have important clinical implications for the management of patients with verbal memory impairment.

In this cross-sectional study, we aimed to assess the contributions of cerebral cortex and hippocampal subfields to verbal memory encoding in temporal lobe epilepsy. We included consecutive patients (n = 84) with radiologically and pathologically defined hippocampal sclerosis (44 left-sided) and unilateral temporal lobe epilepsy, and healthy volunteers (n = 43) who were comparable regarding age and sex. The morphometric and volumetric measures of cerebral cortex and hippocampal subfields were extracted from high-resolution MRI scans. People included in this study underwent standardized neuropsychological evaluation, including measures of verbal memory assessed through the Adult Memory and Information Processing Battery. Verbal memory performances were z-scores corrected by using means and standard deviations published for sample standardization. Associations between verbal learning z-scores and the gray matter volume of the cerebral cortex and hippocampal subfields were investigated.

Reduction of gray matter volumes in the left and right medial and dorsolateral pre-frontal cortex (pcorr < 0.0001), superior and middle temporal gyri (pcorr < 0.0001), anterior and posterior cingulate cortex (pcorr < 0.0001), and of the left ventrolateral PFC (pcorr < 0.0001) and parietal-temporal-occipital junction (pcorr < 0.0001) were associated with worse verbal learning. These findings were consistent across both the entire cohort and in a subgroup analysis focused exclusively on hippocampal sclerosis patients. Within hippocampi, smaller volumes of the left dentate gyrus (p = 0.003), cornu ammonis 4 (p = 0.005), and cornu ammonis 3 (p = 0.03) were associated with worse verbal learning z-scores.

This study demonstrates that verbal learning in patients with temporal lobe epilepsy is strongly related to the volume of distinct regions of the prefrontal, temporal, and cingulate cortices and left dentate gyrus, cornu ammonis 4, and cornu ammonis 3 hippocampal subfields. It provides the basis to suggest a corticohippocampal network for verbal learning in these patients, improving our understanding of human verbal memory. These biomarkers may inform attractive targets for forthcoming modulating therapies. Future work may also analyze the impact of sparing part of the left dentate gyrus, cornu ammonis 4, and cornu ammonis 3 as a protective measure against verbal memory impairment after surgery for temporal lobe epilepsy.
Vitamin B6 catabolism and psoriasis risk: A cross-sectional study
Authors: Bai Ruimin , Cheng Xiaoqing , Yang Yajie , Zhang Jian , Tian Qiong
Published: February 2025

Background

Psoriasis is a common autoimmune inflammatory disease. Vitamin B6 is crucial for the body’s inflammatory response, yet the relationship between pyridoxal 5'-phosphate (PLP), 4-pyridoxic acid (4-PA), and vitamin B6 turnover (4-PA/PLP) in psoriasis remains unexplored.

Objective

To investigate the relationship of PLP, 4-PA and vitamin B6 catabolism with the risk of psoriasis.

Methods

This cross-sectional study analyzed 7,540 participants from the National Health and Nutrition Examination Survey. Vitamin B6 catabolism was assessed via the serum 4-PA to PLP ratio (4-PA/PLP). The primary outcome was psoriasis, evaluated using weighted univariate and multivariate logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI). Subgroup analyses were performed by age, gender, body mass index (BMI), hypertension, dyslipidemia, and cardiovascular disease (CVD).

Results

Out of the participants, 208 had psoriasis. After adjusting for confounders, 4-PA levels in cutoff above group were positively associated with psoriasis (OR=1.51, 95% CI: 1.03-2.20). Additionally, 4-PA/PLP correlated with increased psoriasis risk (OR=1.82, 95% CI: 1.02-3.26). However, PLP levels did not show a significant association. The positive link between 4-PA/PLP and psoriasis was consistent in individuals with BMI ≥25 kg/m², hypertension, and those without dyslipidemia.

Conclusion

The results revealed significant association of 4-PA and 4-PA/PLP level with the presence of psoriasis. However, further extensive prospective studies are necessary to establish causality.
Dermoscopic Features of Ethnic Acral Melanosis in Fitzpatrick Skin Types IV-VI
Authors: Rodriguez Elijah , Sher Elizabeth F , Juarez Michelle , Polsky David , Johnson James , Stein Jennifer A , Adotama Prince
Published: February 2025

Ethnic acral melanosis is a pigmentary abnormality found on the acral surfaces of patients of color, about which little is known. Patients of darker Fitzpatrick types have not been well represented in the limited studies that have been published on this topic, calling for more research on ethnic acral melanosis, particularly in patients of color. This is the largest case study to date of patients with Fitzpatrick skin types IV-VI that describes the dermoscopic findings of ethnic acral melanosis.
Troponin I is an independent predictor of cardiovascular events and mortality in haemodialysis patients
Authors: Tydén Maria , Westerlund Magnus E , Duarte Kevin , Eriksson Niclas , Girerd Nicolas , Krämer Bernhard K , März Winfried , Rossignol Patrick , Scharnagl Hubert , Soveri Inga , Svensson Maria K , Zannad Faiez , Fellström Bengt
Published: February 2025

Background

Patients with end-stage kidney disease (ESKD) undergoing haemodialysis (HD) have a high risk of cardiovascular (CV) events. This study evaluated Troponin I (hs-cTnI) as a predictor of major adverse cardiac events (MACE), CV- and all-cause death.

Methods

The AURORA trial, a multicentre, randomized, double-blind trial involved 2776 HD patients comparing Rosuvastatin to placebo. No significant effect was found on the composite primary endpoint of CV death, nonfatal myocardial infarction or nonfatal stroke. In this post-hoc analysis, we analysed the association between baseline hs-cTnI and outcomes using Cox-regression analyses. We adjusted for multiple background factors and available biomarkers. Hs-cTnI was log2 transformed and modelled using a four-knot restricted cubic spline. Variables were ordered by their importance in the models using χ2 value minus degrees of freedom.

Results

Baseline median hs-cTnI was 17.3 pg/mL. During follow-up, 734 MACE, 598 CV deaths, and 1094 total deaths occurred. Patients in the upper quartile of hs-cTnI (>32.6 pg/mL) had significantly higher risk of MACE (HR 1.92; 95% Confidence interval [CI] 1.57-2.35), CV death (HR 2.12; 95% CI 1.69-2.66), all-cause death (HR 1.84; 95% CI 1.55-2.17) and non-CV death (HR 1.59; 95% CI 1.23-2.05) after full adjustment compared to those in the lowest quartile (<10.1pg/mL). Hs-cTnI was identified as the strongest predictor for MACE, CV death, and all-cause death, but not for non-CV death.

Conclusion

Baseline hs-cTnI is a strong and independent predictor for MACE and death in patients end-stage kidney disease (ESKD) undergoing haemodialysis (HD).
Hormonal regulation of human adipose tissue lipolysis: impact of adipose GIP system in overweight and obesity
Authors: Brachs Sebastian , Soll Dominik , Beer Finja , Huckauf Nadine , Konkar Anish , Spranger Joachim , Rütten Hartmut , Mai Knut
Published: February 2025

Objective

Given the promising effects of GLP-1/GIP/glucagon receptor triagonists on weight loss in animals and humans, improved understanding of underlying mechanism is required. We investigated a direct lipolytic effect of a specific GLP-1/GIP/glucagon receptor triagonist on human adipose tissue to disentangle central and peripheral effects as potential drivers of weight loss.

Design and methods

Isolated primary adipocytes from subcutaneous adipose tissue biopsies of 22 non-diabetic subjects [63.0 (57.0-69.5) years] were incubated with increasing concentrations of isoprenaline, GLP-1, GIP, glucagon, or a GLP-1/GIP/glucagon receptor triagonist. Glycerol concentration was measured following stimulation to assess lipolysis. mRNA expression of adipose tissue receptors was analyzed in parallel.

Results

Glycerol concentration only increased by isoprenaline, GIP (+13%), and GLP-1/GIP/glucagon receptor triagonist (+28%) but not by GLP-1 or glucagon. This effect was not related to age or body mass index (BMI). Higher adipose tissue GIP receptor mRNA expression was related to elevated glycerol release after GIP and GLP-1/GIP/glucagon receptor triagonist stimulation.

Conclusions

Direct lipolytic effects of GIP seem to exist in human subcutaneous adipose tissue. This might be targetable by multiple receptor agonists, especially with a high GIP receptor affinity. Such a mechanism can potentiate the beneficial effect on weight loss and will therefore represent a promising target of future research.

Clinical trial registration number

The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.
Addressing the challenges of acute toxicity hazard classification using a non-animal defined approach
Authors: Macmillan Donna S , Ambure Pravin , Aranda Vicente , Bayona Yannick , Bonderovic Vera , Dawick James , Fabre Nicolas , Fischer Stephan , Hodges Geoff , Llobet-Mut Ágata , Loisel-Joubert Sophie , Rivetti Claudia , Roberts Jayne , Schirmer Kristin , Serrano-Candelas Eva , Serrano Ramón Blanca , Stackhouse Ricky A
Published: February 2025

Acute fish toxicity is an ecotoxicological endpoint which provides important information about a chemical’s potential to elicit adverse effect(s) on fish. These effects are typically studied using in vivo tests but for animal welfare reasons as well as the quest for increased species relevance, biological coverage, mechanistic understanding of effects and throughput, there have been significant efforts in recent years to reduce or replace the use of animals in (eco)toxicological hazard assessment, by developing defined approaches (DA) or integrated approaches to testing and assessment (IATA). To this end, a novel score-based DA has been developed, which integrates three in silico predictions from freely available (Q)SARs: the VEGA Fish (KNN-Read-Across) and Fathead Minnow (KNN-IRFMN) models and the United States Environmental Protection Agency (USEPA) ECOSAR Fish 96-h LC50 model, along with in vitro RTgill-W1 data. The DA provides a categorical output aligned with the United Nations Globally Harmonized System of Classification and Labelling (GHS) framework (Acute Category 1, Acute Category 2, Acute Category 3 or Not Classified) with an overall accuracy of 80%, offering a reliable alternative to traditional in vivo testing methods for acute fish toxicity.
May Measurement Month 2022: an analysis of blood pressure screening results from South Africa
Authors: Woodiwiss Angela J , Orchard Ane , Kolkenbeck-Ruh Andrea , Ware Lisa J , Mels Catharina M C , Yates Samantha , Prakaschandra Rosaley , Jones Erika S W , Pillay Sarusha , Beaney Thomas , Kerr Gabriele , Poulter Neil R
Published: February 2025

The May Measurement Month (MMM) campaign was carried out in South Africa in 2022 with the aim of raising awareness of raised blood pressure (BP). Here, we report on the findings of the campaign.

Adults aged ≥ 18 years were recruited opportunistically at university campuses, community centres, schools, sport complexes, public parks, shopping centres, hospitals, and through household visits. Three seated BP readings were taken for each participant, along with completion of a questionnaire on demographics, lifestyle factors, and comorbidities. Hypertension was defined as a systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Controlled BP was defined as being on antihypertensive medication with a BP <140/90 mmHg. Multiple imputation was used to estimate any missing BP readings. In total, 4602 were screened, with a mean age of 31.9 years and 61.9% of whom were female. Of all participants, 1217 (26.5%) had hypertension, of whom 456 (37.5%) were aware, and 406 (33.4%) were on antihypertensive medication. Of those on antihypertensive medication, 205 (50.5%) had controlled BP, and of all participants with hypertension, 16.8% had controlled BP.

The MMM campaign in South Africa identified significant numbers of participants with either untreated or inadequately treated hypertension. The high prevalence of hypertension, despite the young adult age, together with the high proportions of individuals unaware of their hypertension and with uncontrolled BP highlight the need for hypertension screening and awareness campaigns, and more rigorous management of hypertension.
Comprehensive mapping of individual living and dead tree species using leaf-on and leaf-off ALS and CIR data in a complex temperate forest
Authors: Lisiewicz Maciej , Kamińska Agnieszka , Kraszewski Bartłomiej , Kuberski Łukasz , Pilch Kamil , Stereńczak Krzysztof
Published: February 2025

Tree species information is crucial both for understanding forest composition and supporting sustainable forest management, but also for monitoring biodiversity and assessing ecosystem services. Remote sensing data has been widely used to map the spatial distribution of tree species across large areas. However, there is currently a lack of studies demonstrating the potential of airborne laser scanning data collected during different seasons to identify multiple individual tree species/genera, including dead individuals. The main objective of this study was to map the ecologically valuable forest area constituting the Polish part of the Białowieża Forest using leaf-on and leaf-off airborne laser scanning (ALS) data and color-infrared imagery. Eleven living species/genera (alder, ash, aspen, birch, hornbeam, lime, maple, oak, pine, spruce and other deciduous) and four dead classes (dead deciduous, dead pine, dead spruce and snag) were classified at the individual tree level. Applying the Random Forests algorithm and a set of 30 predictor variables, 15 classes were classified with an overall accuracy of 82 per cent. The mapping of nearly 20 million individual trees revealed that in 2015, the most common tree species in the upper part of the Białowieża Forest stands was spruce (20.1 per cent), followed by alder (19.0 per cent) and pine (18.1 per cent). Among dead trees, dead deciduous trees (2.2 per cent) and dead spruce (1.7 per cent) were the most common. Our results can serve as a first cornerstone for carrying out further in-depth analyses of forest biodiversity using remote sensing data in this exceptional forest area.
Unpacking family meals: state-of-the-art review critiquing the Western ideals, positioning and promotion of family meals
Authors: Le Moal Fairley , Litterbach Eloise-kate , Dunn Katherine , Fraser Kylie , Bouchaud Celeste C , Middleton Georgia
Published: February 2025

Family meals are a familiar concept and are practised in many Western households. While academics have been researching family meals for decades, there is much about the family meal we still do not understand. Meanwhile, the promotion of an ‘ideal’ of family meals across media, health and social discourse ensues. An extensive pool of research has indicated cross-sectional associations between the frequency of family meals and optimal health outcomes. However, evidence surrounding what specifically it is about the family meal that could offer health benefits is limited. Furthermore, family meals carry a level of moral value, evoking pressure for parents to ‘achieve’ a family meal ideal, unattainable for many. Family meals research has traditionally focussed on mothers’ perceptions and roles in family mealtimes. While literature is starting to emerge on the often-overlooked cognitive contribution required to plan and execute family meals, little structural supports exist to streamline these efforts or make them more achievable for contemporary families. The published literature is only starting to include cultural and demographic diversity, making it difficult to understand and promote realistic and feasible family meals across populations. The popular depiction of family meals needs to evolve alongside changes in social norms. Our call to action to address these issues is to draw on existing family meal practices, continue to diversify our investigations, and broaden our definitions and understandings of what a family meal is or could be, and how it should be measured.
From statistical physics to social sciences: the pitfalls of multi-disciplinarity
Authors: Bouchaud Jean-Philippe
Published: February 2025

This is an adapted version of my inaugural lecture at Collège de France in 2021. I reflect on the difficulty of multi-disciplinary research, which often hinges on unexpected epistemological and methodological differences, for example, about the scientific status of models. What is the purpose of a model? What are we ultimately trying to establish: rigorous theorems or ad hoc calculation recipes; absolute truth, or heuristic representations of the world? I argue that the main contribution of statistical physics to social and economic sciences is to make us realize that unexpected behavior can emerge at the aggregate level, which isolated individuals would never experience. Not only crises, panics, opinion reversals, the spread of rumors or beliefs, fashion effects, and the zeitgeist but also the existence of money, lasting institutions, social norms, and stable societies must be understood in terms of collective belief and/or trust, self-sustained by interactions, or on the contrary, the rapid collapse of this belief or trust. Agent-based models provide a powerful and natural framework to account for such phenomena.
A review of anthropogenic hazardous particulate matters: general description and adsorbent materials
Authors: Yang Jiaren , Shi Lin , Shi Fengcheng , Kuang Ying , Qian Hong , Wang Lejun , Zhang Ting , Jiang Fatang
Published: February 2025

Anthropogenic hazardous particulate matters (AHPM) refers to small airborne particles generated by human activities. This review aims to summarize the basic information on the classification, source, and distribution pattern of AHPM and its hazards. The classification of different adsorbent materials is summarized. Based on the characteristics of various adsorbent materials, the trend of new adsorbent materials in the future development is proposed. This provides researchers with new ideas for the study of adsorption of AHPM and gives an outlook on the research of new adsorbent materials and describes their potential application value.
SARS-COV-2-DRIVEN EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING AND THE COVID19-ASSCOCIATED PSYCHOSIS/SCHIZOPHRENIA
Authors: Nawa *Hiroyuki
Published: February 2025

Background

COVID-19 presents a wide range of symptoms, including respiratory issues and, intriguingly, neurological and psychiatric manifestations such as delirium and psychosis as well. Pathological studies reveal that the cytokine storm, particularly involving the activation of the epidermal growth factor receptor (EGFR), plays a crucial role in viral replication and the development of lung fibrosis. Notably, the spike domain of SARS-CoV-2 mimics EGF and directly triggers EGFR activation before inflammation occurs, suggesting new therapeutic options involving anti-EGFR kinase inhibitors to combat COVID-19 fibrosis. However, this finding regarding the biological activity of the spike protein also raises concerns about current and future psychiatric disorders associated with COVID-19.

Method

Recombinant EGF or SARS-CoV-2 spike protein is subcutaneously administered to neonatal mice, hamsters, and rats during their postnatal period. After 2-3 months, these animals undergo neurobehavioral tests and physiological recordings with institutional authorization.

Results

We are exploring the connections between EGFR signaling and schizophrenia, revealing significant molecular associations of the EGFR system in the blood and brain tissue of patients. Animal models exposed to EGF or the other EGFR ligands during perinatal stages exhibit various behavioral endophenotypes relevant to schizophrenia, including abnormalities in ASSR, d/fMMN, P300, ABR, and frontotemporal connectivity. The animal models also exhibit behavioral changes, especially an increase in dopaminergic activity post-puberty and neuronal hyperactivity in the auditory cortex, correlating with the onset of their behavioral impairments.

Discussion & Conclusion

This comprehensive discussion with the EGF animal model delves into the neuropsychiatric implications of prognostic symptoms of COVID-19 and their interaction with the EGFR system. However, the severity and prevalence of neurological/ psychiatric symptoms vary among COVID- 19 patients, and not all individuals with the virus experience CNS involvement. Further studies will help clarify the role of EGFR signaling in psychiatric symptoms and consequences in the context of COVID-19.
THE EFFECT OF DOPAMINE RECEPTOR D1 (DRD1) GENE VARIANTS ON CHANGES IN CRAVING SEVERITY DURING ALCOHOL WITHDRAWAL
Authors: Lin *Ze-yu , Huang Ming-Chyi , Lee Pin-Wei , Liu Tung-Hsia , Liu Yu-Li
Published: February 2025

Background

Alcohol dependence (AD) is a complex disorder with unclear underlying etiologies. One strategy to understand its pathophysiology involves investigating the behaviors or symptoms, namely subphenotypes, associated with AD. Given that aggression is a prevalent behavior in individuals with AD and is associated with a poor outcome, we attempted to examine the biological underpinnings of aggression as a subphenotype of AD in terms of genetic predisposition. Furthermore, we also explored the impact of genes on craving, a hallmark of AD and AD relapse.

Aims & Objectives

This study aimed to identify the association of aggression-related candidate genes with AD. In addition, we also investigated the genetic association with changes in craving severity following 2 weeks of alcohol withdrawal.

Method

A total of 210 treatment-seeking patients with AD and 117 healthy controls were recruited in this study. 7 candidate genes were screened based on genome-wide genotyping Axiom Genome-Wide TWB 2.0 Array, included MECOM, AVPR1A, DRD1, DRD2, DRD3, RBOX1, and HTR2A. We followed the Alcohol Craving Questionnaire-Short Form-Revised (ACQ-SF-R) and Obsessive-Compulsive Drinking Scale (OCDS), both of which were used to assess the severity of alcohol craving during withdrawal.

Results

Among the candidate genes, we identified a significant association of Dopamine Receptor D1 ( DRD1) gene with AD. The DRD1 single nucleotide polymorphisms (SNPs) (rs12518222, rs144667196, rs4867798, rs686, rs4532, rs5326, and rs265981) were further examined, and we found these SNPs were significantly associated with AD. The minor alleles of rs12518222, rs4867798, rs686, rs4532, rs5326, rs265981 were associated with higher craving scores throughout the withdrawal period.

Haplotype-based analyses also demonstrated a significant association of DRD1 gene with less craving alleviation during alcohol withdrawal.

Discussion & Conclusion

Our data indicates an association between the aggression-related gene DRD1 and AD within Taiwanese population. Particularly, patients harboring the minor alleles of DRD1 SNPs have a higher risk of AD and display a higher post-withdrawal craving scores compared to those harboring their counterparts. These findings, indicating that DRD1 gene plays a role in the susceptibility to AD and retards craving amelioration during the recovery phase, suggest that aggression might intricately involve neurobiological mechanisms contributing to AD.
SUPPLEMENTING WITH DEXTROMETHORPHAN MAY ENHANCE COGNITIVE FUNCTIONS IN YOUNG INDIVIDUALS WITH BIPOLAR DISORDERS
Authors: Huang *Chih-Chun , Chang Yun-Hsuan , Lu Ru-Band , Hong Jau-Shyong
Published: February 2025

Background

Bipolar disorder (BD) is a chronic, debilitating mental condition with consistent prevalence across genders and ethnicities. It's marked by high relapse rates, mood swings, and disruptions in various life aspects. Prior research has highlighted neuropsychological impairments in BD.

Aims & Objectives

This study investigates the therapeutic effect of dextromethorphan (DM), an open- label drug, and its influence on different age groups' neuropsychological functions in BD patients.

Methods

We recruited 92 BD patients, with 55.1% males. In a 12-week, randomized, double-blind study, we assigned patients to one of three groups: 29 on valproic acid (VPA) plus either placebo (VPA+P) or 63 with DM (30 mg per day or 60mg per day). We evaluated symptom severity using the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS). Patients completed neuropsychological tasks at baseline and after the 12-week trial: the Wechsler Memory Scale (WMS) and the Continuous Performance Test (CPT). We also recorded clinical characteristics.

Results

Patients showed overall improvement in all neuropsychological functions after the 12-week trial. Subgrouping patients by age, the younger group (YG, younger than 39 years old) responded more positively to DM treatment, while the middle-old group (MOG, older than 40 years) exhibited less pronounced effects.

Discussion & Conclusion

This study provides valuable insights into DM's therapeutic effect, aligning with previous research. Age played a role in the therapeutic response, particularly among younger BD patients. Early treatment may yield better neuropsychological outcomes. To comprehensively capture neuroplasticity and therapeutic impact, especially on memory indices of WMS-III, we recommend future longitudinal studies. These would shed light on the long-term impact of age on BD patients' multifaceted functions.
CHANGES IN CORE DEPRESSIVE SYMPTOMS OVER TIME IN PERIPARTUM WOMEN: A NETWORK ANALYSIS
Authors: Zhang *Yuqun , Gao Ju , Qin Meixia , Zhao Weiying , Ding Yi , Chen Ying , Qiao Xuebin , Yue Xin , Yuan Yonggui
Published: February 2025

Background

Perinatal depression (PND) is common in pregnant and postpartum women. Previous research indicates that there are clinical subtypes of PND, and the time of onset is an important factor to identify PND subtypes. However, differences of PND in different trimesters and in the postpartum period are not clear. And studies examining core symptoms that could be used to identify PND subtypes are lacking.

Methods

Women during the second (N = 161) and third trimesters (N = 248) and within 6 weeks postpartum (N = 110) were recruited. All participants completed the assessment of the Edinburgh Postnatal Depression Scale. Network analysis was used to explore the relationships between depressive symptoms in all three periods.

Results

Postpartum women showed the highest prevalence of PND and the most severe depressive symptoms. The symptom ‘Sadness and misery’ had the strongest centrality in both the second and third trimesters, but decreased in the postpartum period. The symptom ‘Fear and panic’ had the strongest centrality in the postpartum period. All three PND networks were relatively stable in strength and closeness.

Conclusions

This study indicated the changes over time in central symptoms in pregnant and postpartum women, which shifted from being dominated by depression to being dominated by anxiety. Our findings suggested that more symptom-specific interventions should be used to improve the mental health of mothers, fetuses and infants. All of this provided clinical evidence to investigate the biological mechanisms of PND subtypes to help diagnose and treat PND with precision.
GHRELIN SIGNALLING MEDIATES SEX DIFFERENCES IN MIDBRAIN CONTROL OF BINGE DRINKING
Authors: Walker *Leigh C , Pearl Amy , Pinares-Garcia Paulo , Shesham Arnav , Maddern Xavier , Anversa Roberta G , Reed Felicia , Giardino William J , Lawrence Andrew J
Published: February 2025

Background

The circuitry mediating excessive alcohol consumption includes the understudied central projecting Edinger-Westphal (EWcp); a structure dense in neuropeptide expression, including cocaine and amphetamine regulated transcript (CART). While studies have shown a critical role for this nucleus in alcohol consumption, few studies have interrogated the contributions of distinct EWcp populations.

Aims

We aimed to understand the contribution of peptidergic EWcp cells in alcohol consumption, and hypothesized sex differences may be present.

Methods

To examine a functional role of these cells in binge drinking we used chemogenetics to inhibit EWcppeptidergic cells in male and female CART-Cre mice. We next used RNAscope to examined the neurochemistry of EWcppeptidergic cells observing strong overlap with the ghrelin receptor (GHSR) and using whole cell patch clamp electrophysiology, we assessed the response of EW peptidergic cells to bath application of ghrelin in male and female mice. Next, we knocked down Ghsr expression non-specifically in the EWcp of male and female mice using a shRNA and specifically from peptidergic (CART-Cre) and glutamatergic (vGlut2-Cre) populations using Cre-dependent Ghsr-shRNA. Finally, given ghrelin has high constitutive activity, we assessed whether a ghrelin antagonist (JMV2959) or inverse agonist (LEAP2) could reduce binge drinking when administered directly within the EW nucleus.

Results

Chemogenetic inhibition of EWcppeptidergic cells had no effect on binge drinking, anxiety behaviour or other consummatory behaviours in male mice; however, a specific reduction in alcohol binge drinking was observed in female mice. Ghsr mRNA was strongly expressed in EWcppeptidergic, and to a lesser extent in EWcpglutamatergic cells. Further, bath application of ghrelin increased firing frequency in EWcppeptidergic cells in both male and female mice, however, the change in response was significantly higher in females. Systemic ghrelin administration increased binge drinking in female mice, which was reduced by chemogenetic inhibition of EWcppeptidergic cells. In addition, non-specific EWcp Ghsr-shRNA knockdown reduced binge drinking specifically in female, but not male mice compared to scram-ShRNA controls.

Further in female mice, Ghsr-shRNA localised to EWcppeptidergic, but not EWcpvGlut2 cells reduced binge drinking. Finally, infusion of both a GHSR antagonist and inverse agonist directly within the EWcp reduced binge drinking in female mice.

Conclusions

Together, our results suggest the EWcp is a region mediating excessive alcohol bingeing through GHSR actions on peptidergic cells in female mice. Given the recent interest in GHSR1a inverse agonists for the treatment of alcohol use disorder, understanding the neural mechanism(s) underpinning how the ghrelin system mediates alcohol consumption are critical.
NPAS4 ENHANCER RNA FORMS DNA:RNA HYBRID R-LOOP TO CONTROL REWARD-RELATED BEHAVIORAL ADAPTATION THROUGH ACTIVITY-DEPENDENT GENE EXPRESSION
Authors: Akiki Rose Marie , Magami Kosuke , Cornbrooks Rebecca G , Greige Alain , Snyder Kirsten K , Wood Daniel J , Herrington Claire M , Mace Philip , Blidy Kyle , Koike Nobuya , Berto Stefano , Cowan Christopher W , Taniguchi *Makoto
Published: February 2025

Neuronal activation induces immediate early response genes expression, essential for behavioral adaptation to emotional stimuli. Npas4 is rapidly induced by synaptic activity, regulating behavioral responses to cocaine reward conditioning and chronic stress. A novel long non-coding RNA (LncRNA) transcribed from Npas4 enhancer is identified as essential for emotional stimuli-induced Npas4 mRNA expression and formation of cocaine reward-associated context in NAc and chronic stress-induced deficits in sucrose preference in mPFC. Notably, LncRNA forms DNA:RNA hybrid structure R-loop, required for synaptic activity-dependent Npas4 mRNA expression through regulating 3D chromatin loop structure connected between Npas4 promoter and enhancer. The findings highlight an unprecedented mechanism of LncRNA function through the formation of R-loop for 3D chromatin loop structure, providing novel insights into the regulation of synaptic activity-dependent gene expression.
A CASE STUDY OF COMPREHENSIVE TREATMENT ON GAMBLING DISORDER IN ADOLESCENTS: NOVEL CHALLENGES IN LOW MIDDLE INCOME COUNTRY
Authors: Murtani *Belinda Julivia , Siste Kristiana , Hanafi Enjeline
Published: February 2025

Background

Gambling disorder is growing extensively in Indonesia, with the estimated prevalence in 2021 is around 1%. This figure is in line with the global prevalence, which is in the range of 0.1% to 5.8%. Recent years have seen a rise in the availability of gambling activities, particularly online gambling during the COVID- 19 pandemic and easily approved online loans. Furthermore, this issue became more complicated due to a lack of effective regulation and public awareness, impacting not just individuals but also families and society as a whole. There have been documented negative impacts of gambling disorder, such as damaged relationships, loss of employment, financial hardships, and a greater chance of mental health problems like anxiety and depression. However, treatment options and support services for people with gambling disorder are still limited in Indonesia. Adolescents with gambling disorders are particularly difficult to manage because they are still connected to their peers and find it difficult to cut back on technology use that encourages online gambling. Additionally, adolescents with immature prefrontral cortex also have poorer decision making skills and are more impulsive, thereby raising their risk of developing a gambling disorder.

Aims

The aim of the present study was to manage gambling disorder using a multi-modal approach including pharmacological and psychotherapy

Case-description

A 18-year-old male, was brought by his parents to an out-patient psychiatric clinic because his online gambling had gotten worse over the past five months. He also had premorbid antisocial personality disorder and tobacco use disorder, along with a family history of substance abuse that included his father and paternal grandmother. He had the background of progessively increasing engagement in online gambling for the past one year with consequent financial difficulties, school problems and relationship problems. His primary goal when playing online roulette, slots, and black jack was to win money, thus he could go out with friends. The patient took online loan and embezzled funds from the mosque savings, parents, uncle, and aunt. According to DSM-V, he was diagnosed with gambling disorder. He received cognitive behavioral therapy and motivational enhancement therapy at first.

Subsequently, he was prescribed 50 mg of sertraline and 10 mg of clobazam for his mood irritability brought on by the limitations of his gadget, which he also attempted to manipulate his parents in order to gain access to the gadget. Additionally, contingency management was added to improve the course of treatment.

Conclusion

The management of gambling disorders should involve a thorough treatment plan that uses a multimodal approaches. The patient has responded well and promptly to the therapeutic approaches used. Specific tailor-made therapeutic approaches for each individual need to be developed.
EXPLORING THE IMPACT OF CHILDHOOD NEGLECT ON COGNITIVE FUNCTION IN PATIENTS WITH BIPOLAR DISORDER
Authors: Hsueh *Yuanzhi , Huang Cho-Yin , Kuo Po-Hsiu , Cheng Ying-Chih , Huang Ming-Chyi , Chiu Chih Chiang , Kuo Chian-Jue , Chen Po-Yu , Chen Wen-Yin
Published: February 2025

Background

Bipolar disorder (BD) is a severe mental disorder associated with neurocognitive deficits. The exposure to childhood trauma experiences is also linked to poorer cognitive performance. However, there is limited reporting on the distinct compositions of childhood trauma in BD and their specific impacts on cognitive performance.

Methods

In this cross-sectional study, we utilized the Brief Assessment of Cognition in Affective Disorders (BAC-A) to evaluate cognitive performance and the Chinese version of the Childhood Trauma questionnaire-short form (C-CTQ-SF) to assess childhood trauma experiences in a sample of 55 euthymic BD patients. We applied Two-Step cluster analysis to dissect their childhood trauma experiences, revealing distinct clusters: a low-trauma group, a neglect-focus group, and a multiple trauma experience group. We compared cognitive function among these three clusters and employed a generalized linear model to assess the impact of childhood neglect trauma on cognitive domains.

Results

The neglect-focus cluster exhibited notably high levels of exposure to physical and emotional neglect (41.8%). Moreover, BD patients in this cluster performed even worse on the BAC-A compared to patients in the multiple trauma cluster, particularly in working memory and processing speed. Using the low trauma cluster as a reference, the neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002), after adjusting for confounding factors.

Conclusions

Distinct patterns of childhood trauma experience are observed in BD patients and are associated with different cognitive profiles. Early exposure to neglect-focus trauma is linked to the poorest cognitive performance in the current study. Further studies investigating the intensity of neglect, as well as individual resilience and coping mechanisms in BD, are warrant.
OXYTOCIN-AUGMENTED MODULAR-BASED GROUP INTERVENTION FOR LONELINESS: A RANDOMIZED-CONTROLLED TRIAL
Authors: Hurlemann *Rene , Berger Ruben , Shamay-Tsoory Simone , Kanterman Alisa , Brausa Maura , Gorni Jessica , Luhmann Maike , Schramm Elisabeth , Schultz Johannes , Philipsen Alexandra , Lieberz Jana , Scheele Dirk
Published: February 2025

Background

Chronic loneliness is associated with increased morbidity and mortality. The COVID-19 pandemic has highlighted the importance of loneliness as a modifiable risk factor for major depressive disorder (MDD) and generalized anxiety disorder (GAD). As a result, there is an urgent need for neurobiologically informed interventions to reduce loneliness (1).

Aims & Objectives

Given preliminary evidence for impaired oxytocin signaling in chronic loneliness (2), the current proof- of-concept study used a randomized, double-blind, placebo-controlled design to probe intranasal oxytocin (IN-OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high chronic loneliness (HL) (Fig. 1).

Method

Seventy-eight healthy HL participants (56 women) received five weekly group psychotherapy sessions targeting negative cognitive biases in loneliness. After a first orientation session, HL participants received IN-OT or placebo before therapy. Trait loneliness was measured at baseline and a week and three months after the intervention. Perceived stress, quality of live, and the therapeutic relationship were assessed at each session, while state loneliness was tested before and after each session. As an additional no-intervention control group, 49 healthy participants reporting low loneliness (26 women) were also tested twice.

Results

The intervention significantly reduced perceived stress and improved trait loneliness, which was still evident at the 3-month follow-up. IN-OT had no significant effect on these primary outcomes or quality of life. However, compared to placebo, IN-OT significantly facilitated the decrease in state loneliness within sessions and significantly enhanced positive aspects of the therapeutic relationship, in the form of improved positive bonding of the therapist with the whole group.

Discussion & Conclusion

Conclusively, the short-term group intervention improved trait loneliness, but IN-OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of IN-OT into long-term benefits.

References

1.Morr M, Liu X, Hurlemann R, Becker B, Scheele D. Chronic Loneliness: Neurocognitive Mechanisms and Interventions. Psychother Psychosom. 2022;91(4):227-237.

2.Patin A, Scheele D, Hurlemann R. Oxytocin and Interpersonal Relationships. Curr Top Behav Neurosci. 2018;35:389-420.
REGIONAL HOMOGENEITY CHANGES IN CEREBRAL AND CEREBELLAR REGIONS ASSOCIATED WITH DEFAULT-MODE NETWORK FOLLOWING PROLONGED INTERMITTENT THETA-BURST STIMULATION
Authors: Cheng *Chih-Ming , Li Cheng-Ta , Bai Ya-Mei
Published: February 2025

Background

The medial prefrontal cortex (MPFC), which is a component of the default-mode network, has been shown to play a role in the pathophysiology of major depressive disorder and treatment-resistant depression (TRD). It has also been discovered that the cerebellum, especially the posterior lobule, exhibited strong connectivity with multiple functional networks, such as default mode and executive control networks. Patients with MDD have also been observed to have aberrant cerebellar-cerebral connectivity. In contrast to conventional seed-based functional connectivity research, studies examining regional connectivity in patients with TRD, such as regional homogeneity (ReHo), receive comparatively less attention. The potential impact of MPFC stimulation by rTMS on regional functional connectivity in the cerebral and cerebellar regions still remains unknown.

Methods

This sham-controlled, double-blind, randomized trial involved thirty patients who had developed treatment-resistant depression (TRD) and were not responding to antidepressants and standard repetitive transcranial magnetic stimulation (rTMS)/prolonged intermittent theta-burst stimulation (iTBS). The participants were randomly assigned to one of three monotherapy groups (standard iTBS-600 pulses, prolonged iTBS-1800 pulses, or sham coil). The brain stimulation targeting the bilateral dorsomedial prefrontal cortex (DMPFC) was performed twice daily for three weeks. All participants received pre- and post-treatment resting-state functional magnetic resonance imaging (rs-fMRI).

Results

Following treatment, ANOVA showed there were different reho signals in the bilateral cerebellum, precuneus and inferior parietal lobe among three groups. Further analysis revealed that the prolonged iTBS group exhibited a substantially higher reho in the bilateral posterior cerebellar lobules when compared to the sham or standard iTBS group. In contrast, the sham group displayed a higher reho in the precuneus and inferior parietal lobes than the prolonged iTBS group. There was no difference of reho between the sham and standard iTBS groups.

Conclusion

Prolonged iTBS regulated regional function homogeneity in the cerebral and cerebellar regions associated with DMN, highlighting the aberrant DMN alterations in the pathology of MDD.
DETERMINATION OF TRYPTAMINE ALKALOIDS AND THEIR STABILITY IN PSYCHOTROPIC MUSHROOMS
Authors: Kuchar *Martin , Gotwaldova Klara , Borovicka Jan , Jurok Radek , Cihlarova Petra , Hajkova Katerina
Published: February 2025

Synthetic psilocybin (PSB), but also the PSB-containing mushrooms are used for psychedelic therapy and microdosing. It is necessary to know alkaloids variability and stability in wild-grown mushrooms. Concentrations of other psychotropic (or potentially psychotropic) tryptamines such as psilocin (PS), baeocystin (BA), norbaeocystin (NB), and aeruginascin (AE) are also relevant. This study aims to determine the concentrations of PSB, PS, BA, NB and AE in a large sample set of mushroom genera previously reported to contain psychotropic tryptamines. Freshly cultivated fruit bodies of Psilocybe cubensis were used for monitoring stability (including storage and processing conditions of fruiting bodies). Mycelium and the individual parts of the fruiting bodies (caps, stipes, and basidiospores) were also examined. The concentration of tryptamines was analyzed using ultra-high-performance liquid chromatography coupled with mass spectrometry. Analytical standards were synthetized in house and UHPLC-MS/MS method was fully validate for quantification of tryptamine alkaloids in mushroom samples. Most mushroom collections were documented by fungarium specimens and/or ITS rDNA/LSU/EF1-α sequencing.The tryptamine concentrations in mushrooms are extremely variable, which could possibly influence the medicinal effect compared to therapy with chemically pure PSB. The storage conditions strongly affected the alkaloids decay and showed that the highest degradation of tryptamines was seen in fresh mushrooms stored at −80° C, and the lowest decay was seen in dried biomass stored in the dark at room temperature.

This study was funded by the Ministry of Health of the Czech Republic (NU21-04-00307).

References

GOTVALDOVA, K., BOROVICKA, J., HAJKOVA, K., CIHLAROVA, P., ROCKEFELLER, A. &KUCHAR, M. 2022. Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids. International Journal of Molecular Sciences, 23.

GOTVALDOVA, K., HAJKOVA, K., BOROVICKA, J., JUROK, R., CIHLAROVA, P. &KUCHAR, M. 2021. Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. Drug Testing and Analysis, 13, 439-446.