Amelioration of tic disorder by Jujuboside A via gut microbiota remodeling and intestinal 5-HT signaling

BackgroundTic disorder (TD) is a common chronic neuropsychiatric condition manifesting during childhood and adolescence. Jujuboside A (JuA) may alleviate TD symptoms; however, the mechanisms underlying its therapeutic effects remain unclear.MethodsWe established a rat model of TD and used histological techniques to evaluate the effects of JuA on pathological changes. We also measured 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels and assessed tryptophan hydroxylase 1 (TPH1) mRNA expression. Finally, we analyzed the gut microbiota composition in fecal samples using 16S rRNA metagenomic sequencing.ResultsJuA administration alleviated pathological changes in rats with TD, increased 5-HT and 5-HIAA levels, and upregulated TPH1 mRNA expression. Compared with no treatment, JuA treatment increased the proportion of Bacteroidia, Muribaculaceae, Bacteroidales, and Bacteroidota, while reducing that of Bacilli, Lactobacillaceae, Lactobacillus, Lactobacillales, and Firmicutes.ConclusionThese findings indicate that JuA mitigates TD progression, potentially by remodeling the gut microbiota and regulating 5-HT levels.

Multivariate age-related variations in quantitative MRI maps: widespread age-related differences revisited

This study applied multivariate ANOVA to investigate age-related microstructural changes in the brain tissues driven primarily by myelin, iron, and water content, as observed in MRI (semi-)quantitative R1, R2*, MTsat and PD maps. This is effectively a re-analysis of the data analyzed in a univariate way in a previous publication. Voxel-wise analyses were performed on gray matter (GM) and white matter (WM), in addition to region of interest (ROI) analyses. The multivariate approach identified brain regions showing coordinated alterations in multiple tissue properties and demonstrated bidirectional correlations between age and all examined modalities in various brain regions, including the caudate nucleus, putamen, insula, cerebellum, lingual gyri, hippocampus, and olfactory bulb. The multivariate model was more sensitive than univariate analyses, as evidenced by detecting a larger number of significant voxels within clusters in the supplementary motor area, frontal cortex, hippocampus, amygdala, occipital cortex, and cerebellum bilaterally. Though when cross validating the results by splitting the data into 2 subsets, sensitivity is strongly reduced, even more so for the multivariate approach. The examination of normalized, smoothed, and z-transformed maps within the ROIs revealed concurrent age-dependent alterations in myelin, iron, and water content. These findings contribute to our understanding of age-related brain differences and provide insights into the underlying mechanisms of aging. The study emphasizes the importance of multivariate analysis for detecting subtle microstructural changes associated with aging when dealing with multiple quantitative MRI parameter maps.

Neurocognitive function among individuals with problematic social media use

BackgroundWith the development of technology and the internet, social networks gained momentum quickly and play a central role in daily activities. Despite this, there is a public health concern over excessive or problematic social media use. There is also a debate whether excessive social media use should be considered as a behavioral addiction characterized by impulsivity or an impulse control disorder characterized by compulsivity. The goal of this study is to use neurocognitive tasks to investigate impulsivity and compulsivity among excessive social media users compared with non-excessive users.MethodThe study included 79 participants (age range 18 to 37), divided into two groups: 34 participants who excessively use social media (Mean Age = 23.03, SD = 2.71) and 45 participants who do not excessively use social media (Mean Age = 25.47, SD = 4.3). Participants filled out a demographic questionnaire, questionnaires on social media use, impulsivity, compulsivity, anxiety, and depression. They performed computerized cognitive tasks: GO/NO-GO (with Facebook and traffic sign pictures), Experimental Delay Discounting (EDT), and the Wisconsin Card Sorting Test (WCST).ResultsExcessive users of social media exhibited a lower ability to delay gratification on the EDT, indicating impulsivity. They made fewer non-perseverative errors on the WCST, which indicated high flexibility and test shifting, which is a contradicting evidence for compulsivity. Furthermore, on the GO/NO-GO task, individuals who excessively use social media made more omission errors in response to the “Facebook” sign compared to traffic signs (GO condition), indicating impaired selective attention. Finally, they also showed higher subjective ratings of anxiety, depression, impulsivity, and compulsivity.DiscussionThe results of this study provide evidence for impulsivity indicated by delay discounting tendency, which supports the behavioral addiction model, impaired selection attention and lack of evidence for compulsivity in excessive social media users. Further research on neurocognitive function in excessive social media users is required in order to determine whether it should be considered a behavioral addiction or an impulse control disorder.

Microstructural abnormalities in the ATR and VOF underlie tone awareness deficits in Chinese children with developmental dyslexia: a DTI study

ObjectiveTone awareness is crucial for reading in Chinese children, significantly affecting those with developmental dyslexia (DD). This paper identifies microstructural abnormalities in the inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), anterior thalamic radiation (ATR), and vertical occipital fasciculus (VOF) in Chinese children with DD and evaluates their potential relationships with tone awareness and DD.Methods35 children with DD and 64 typically developing (TD) children were recruited from Guangdong Province, China. Diffusion tensor imaging (DTI) measured mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA). The Tone Awareness Judgment Task was used to measure tone awareness. Generalized linear regression and mediation models were used to explore associations and mediating effects.ResultsChildren with DD showed significantly lower MD, AD, and RD values in the bilateral IFOF and ATR, and right VOF compared to TD children, with no significant FA abnormalities. Limited associations between white matter microstructure and tone awareness were observed in the bilateral ATR and right VOF, but these associations did not survive multiple-comparison correction. Tone awareness mediated the relationships between microstructural abnormalities in the bilateral ATR and right VOF and DD.ConclusionsMicrostructural abnormalities in the bilateral ATR and right VOF may be related to DD partly through tone awareness, although direct associations between tract microstructure and tone awareness were limited.

Heatwave-related variations in psychiatric consultations and admissions: a time-series analysis

BackgroundHeatwaves are becoming increasingly frequent and intense across Europe, posing significant risks to physical and mental health. Emerging evidence suggests that prolonged exposure to high temperatures may exacerbate psychiatric symptoms and increase the demand for acute mental health services.ObjectivesThis study examined the relationship between extreme heat events and psychiatric service utilization in Bolzano, Italy, by analyzing emergency psychiatric consultations and acute psychiatric admissions across three non-consecutive years.MethodsA retrospective observational analysis was conducted using daily psychiatric consultations in the Emergency Department (ED) and daily admissions to acute psychiatric wards from 2013, 2018, and 2023. Meteorological data were obtained from the provincial environmental agency. Time-series analyses employed ARIMA models, incorporating daily minimum and maximum temperatures, tropical nights, and a cumulative heatwave index (n_hot_htwv). Model selection was based on BIC, and the effect of exogenous temperature variables was evaluated through changes in AIC. Residual diagnostics guided the inclusion of weekly seasonal dummy variables.ResultsNon-seasonal ARIMA models with day-of-week dummies provided the best fit for both consultations and admissions. Adding the cumulative heatwave variable (n_hot_htwv) consistently improved model fit across all years, whereas minimum and maximum temperatures alone did not. Heatwave duration emerged as a more sensitive predictor of psychiatric service utilization than isolated temperature peaks. No evidence of yearly seasonality was found, and residual diagnostics supported the robustness of models including weekly dummy variables.ConclusionHeatwaves are associated with increased psychiatric consultations and hospital admissions in Bolzano, with cumulative heat exposure representing a critical determinant. These effects cannot be explained solely by seasonal patterns, suggesting an independent climatic influence. Given the projected rise in heatwave intensity and duration, mental health services should incorporate climate-responsive planning and early-warning strategies.

Psychological inflexibility and resilience in anxiety: insights from machine-learning and robust mediation-based models

IntroductionPsychological inflexibility (PI) has been associated with anxiety symptoms, while resilience serves as a protective factor; however, their roles and interrelationship remain poorly understood. We investigated the role of PI on anxiety-related symptoms while assessing the mediating role of resilience and testing the moderating effect of sex and psychiatric history.MethodsFrom April to July 2021, an online protocol employing self-reported measures assessed PI (Acceptance and Action Questionnaire), resilience dimensions (Resilience Scale for Adults), and anxiety-related symptoms (Generalized Anxiety Disorder (GAD) Scale; Depression, Anxiety, and Stress Scales). A model generation approach, using machine-learning and robust mediation-based models, was applied to investigate the relationships between these constructs.ResultsIn a sample of 313 adults (72.20% females; 39.29 ± 11.81 years), Random Forest analysis indicated PI and the resilience dimensions perception of self (R-PS) and planned future (R-PF) as the strongest predictors of anxiety-related symptoms. PI showed a positive direct association with GAD, anxiety, and stress (respectively β = 0.28, β = 0.07, β = 0.20, p ≤ 0.001). Significant indirect associations emerged: PI–Stress regarding R-PS (β = 0.08, p = 0.004), PI–Anxiety regarding R-PF (β = 0.03; p = 0.03), PI–GAD (β = 0.08, p = 0.001) and PI–Stress (β = 0.11, p < 0.001) regarding R-PS and R-PF together.DiscussionThese findings highlight the importance of PI and resilience as interconnected processes underlying mental health outcomes. Additionally, they suggest that psychological intervention programs targeting PI, along with resilience, could foster healthier strategies for coping with anxiety-related symptoms.

The trajectories of Demoralization Syndrome and its related factors among elderly patients with end-stage kidney disease: a longitudinal study

ObjectiveElderly ESKD patients frequently experience a range of psychosocial difficulties, with Demoralization Syndrome (DS) being especially prevalent. This study sought to delineate distinct longitudinal trajectories of DS and to examine factors associated with trajectory membership.MethodsA prospective longitudinal cohort of 363 elderly ESKD patients was recruited from Department of Nephrology in grade a hospital in Anhui, China from January 2023 to December 2025. DS was measured 4 time points from the first hemodialysis session after diagnosis to the 18 month follow-up. LCGM was applied to identify latent DS trajectory classes. Differences among classes were explored with the Two-way ANOVA, Wilcoxon rank-sum test, and multinomial logistic regression was used to assess associations between baseline characteristics and trajectory membership.ResultsThree DS trajectories were identified: Severe Class (54.0%), Moderate Class (41.6%), and Mild Class (4.4%).Membership in the more adverse trajectories was significantly associated with higher use of negative coping styles, lower perceived social support, lower Barthel Index scores, and more negative perceptions of aging (all P < 0.05).ConclusionsConsiderable heterogeneity in DS trajectories exists among elderly ESKD patients, with the majority following a severe pattern. These findings suggest that clinicians should monitor physical and cognitive functioning, regularly assess DS levels, and consider interventions targeting social support and coping strategies to mitigate worsening demoralization over time.

Spatial proteomic analysis in human Alzheimer’s disease brains enables identification of microenvironment-dependent microglial cell states

Nature Neuroscience, Published online: 18 May 2026; doi:10.1038/s41593-026-02267-3

Myeloid cells show marked heterogeneity in Alzheimer’s disease. This study introduces CODEX-CNS, a single-cell spatial proteomics pipeline, and identifies a human microglial subpopulation enriched in Alzheimer’s disease brains that associates with dense amyloid-β plaques.