Epilepsy is a common neurological disorder, often presenting with psychiatric comorbidities and cognitive impairment. Neuroimaging studies have suggested associations between epilepsy and subcortical volumetric abnormalities. The genetic basis between epilepsy and subcortical volume abnormalities is, however, poorly understood, particularly if they share a common genetic architecture.

To investigate polygenic overlap, we employed the bivariate causal mixture model (MiXeR) to analyze genome-wide association data from various epilepsy subtypes (genetic generalized epilepsy [GGE]: n = 49,388, all epilepsy [EP]: n = 69,995, focal epilepsy: n = 57,375) and 16 subcortical volumetric phenotypes (n = 33,224). We identified shared genomic loci through conditional and conjunctional false discovery rate analyses (cond/conjFDR).

MiXeR results suggest substantial shared genetic variants between subcortical volume and common epilepsies. ConjFDR analysis identified 33 distinct shared loci between GGE and subcortical volumetric phenotypes. The shared loci were mapped to 322 protein-coding genes. Among these, 49 genes showed significant expression-trait associations with both GGE and subcortical volume phenotypes, and 12 of the 322 genes were also associated with cognitive, mental health, and personality-related traits.

We dissected the shared genetic architecture between common epilepsies and subcortical volumes. Expression-trait association analyses further identified candidate genes associated with cognitive, mental health, and personality-related phenotypes.

Reliable clinical phenotyping is crucial for diagnosis, treatment, and research in hyperkinetic movement disorders, yet its interrater reliability remains uncertain.

To quantify interrater agreement in clinical phenotyping of hyperkinetic movement disorders among experts in a large, phenotypically diverse cohort.

Within the NEMO project, 161 patients with hyperkinetic movement disorders underwent standardized video assessments. Each patient was independently classified by three international movement disorders experts in a structured, stepwise procedure. Experts first assessed videos alone, then received clinical history and examination, and finally diagnostic test results. At each step, they assigned primary and secondary phenotypes and rated their diagnostic confidence. Interrater agreement was assessed using Fleiss' and Cohen's kappa.

Across all phenotypes, interrater agreement on the primary phenotype increased with added information (κ = 0.457 to κ = 0.607). Agreement with the NEMO reference classification similarly improved (κ = 0.478 to κ = 0.656). Among patients with a single dominant phenotype, agreement reached κ = 0.78. In 93% of cases, at least two out of three experts reached consensus. Agreement was substantially lower in patients with mixed or complex presentations, such as myoclonus-dystonia and functional movement disorders. Diagnostic certainty rose throughout, though secondary phenotype agreement remained poor. Experts rarely revised initial impressions, suggesting robust pattern recognition but also potential confirmation bias.

Movement disorders specialists can reliably identify hyperkinetic phenotypes, even without in-person assessment. While complex, mixed and functional presentations remain diagnostically challenging, our findings reinforce the value of expert phenotyping in clinical care, training, and research, and provide a benchmark for future studies and computational approaches.

Fanconi Anemia (FA) is a rare genetic disorder characterized by bone marrow failure and an increased risk of malignancies. Neuroinflammatory presentations in adulthood are exceedingly rare and pose profound diagnostic challenges, particularly when atypical neurological manifestations closely mimic opportunistic central nervous system infections in an immunocompromised host. We present the complex case of a 32-year-old male with FA who developed a progressive neuroinflammatory syndrome intertwined with infectious processes. The patient presented with fatigue, fever, altered mental status, and gait instability. Initial magnetic resonance imaging (MRI) revealed peripheral enhancing lesions and scattered millimetric calcifications within the cerebrum and cerebellum, clearly delineated on susceptibility-weighted imaging (SWI). Concurrently, a positive CMV PCR raised high suspicion for an opportunistic viral encephalitis, prompting empirical antiviral, antifungal, and broad-spectrum antibiotic therapies. A follow-up contrast-enhanced brain MRI at six weeks demonstrated stability of the lesions. Because severe thrombocytopenia precluded a stereotactic brain biopsy, histopathological confirmation was unavailable. However, the lack of radiological progression argued against an untreated aggressive infectious or neoplastic etiology. While a partially treated opportunistic infection or healed granulomatous disease cannot be definitively excluded, the overall clinical and radiological findings were favored to represent Fanconi Anemia Neurologic Syndrome (FANS). This case highlights the extraordinary diagnostic dilemma of differentiating primary neuroinflammatory syndromes from opportunistic infections in adult patients with FA. Furthermore, it emphasizes the indispensable role of advanced MRI sequences, such as SWI, and longitudinal radiological follow-up in evaluating suspected non-infectious neurological involvement when tissue diagnosis is clinically contraindicated.

Chronic kidney disease (CKD) is associated with lower quality of life (QoL) than the general population, and health education is widely proposed to help patients manage the disease. We conducted a PRISMA-guided systematic review of studies published between 2014 and April 2024 evaluating educational interventions in adults with CKD using a validated QoL instrument. Two reviewers independently selected studies and extracted data, resolving disagreements with a third reviewer; risk of bias was assessed with RoB2 and ROBINS-I. Twelve studies met inclusion criteria. Educational interventions were generally associated with improvements in QoL and clinical parameters, more consistently for mental than physical health, although certainty of evidence was limited by heterogeneity in design, populations and outcomes, and by a predominance of studies with some concerns or high risk of bias. Health education appears a valuable component of CKD care, but well-designed, prospectively registered trials are needed before firm recommendations can be made.

Depression is a clinically relevant comorbidity of Tourette syndrome (TS), yet the organization and development of research on this topic remain poorly characterized. This study aimed to map the knowledge structure, research hotspots, and emerging trends in the literature on TS and depression. It also sought to identify questions that warrant further investigation.

English-language articles and reviews published from 2001 to 2025 were retrieved from the Web of Science Core Collection and Scopus. Bibliometrix, VOSviewer, and CiteSpace were used to analyze publication and citation trends, collaboration networks, co-cited references, keyword co-occurrence, and temporal patterns. A narrative comparison of selected clinical studies informed the interpretation of these findings.

After database-specific screening, 3024 records were combined, and 2311 publications remained after duplicate removal. Publication output increased overall, with the United States, the United Kingdom, and China contributing the most publications. Research themes expanded from tic control and pharmacological treatment to psychiatric comorbidities, mental health, quality of life, and functional outcomes. TS, tic disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, depression, comorbidity, and neuromodulation formed the core keyword network.

Research on TS and depression increasingly addresses psychiatric comorbidity and functional outcomes. These findings support assessing depressive symptoms alongside tic severity and including depression and functional outcomes in future TS research.

Distress during early postnatal life has a potential impact on maternal mental health and related biological systems. However, the potential biological roles of these systems' modifications remain largely unknown. Bronchiolitis represents a life-threatening condition for infants and a possible stressful event for mothers with an impact on maternal breast milk composition and potentially on infants'health. In this framework purposes of the present study were: a) to evaluate the impact of infants' severe bronchiolitis on maternal mental health; b) to examine the correlation between maternal mental health status and extracellular vesicles (EVs) in breast milk; c) to explore the impact of breast milk EVs modification on the infant's innate immunity. We hypothesize that severe infant illness acts as a maternal stressor, which in turn remodels the composition of breast-milk EVs, thereby modulating immune response in the infant affected by bronchiolitis. A prospective, observational study with a case-control design and a longitudinal observation component was conducted. The case group included dyads of mothers and infants, with the infants admitted to the pediatric emergency department for severe bronchiolitis, while the control group consisted of healthy mother-infant dyads. The two groups were evaluated at baseline (admission for bronchiolitis for cases) and after one month. In both the appointments clinical data including mental health status by validated scales and a breast milk sample were collected. Biological analyses included extracellular vesicles (EVs) isolation and characterization, and the use of zebrafish to study the EVs-mediated modulation of innate immunity. Baseline mental health assessment revealed markedly higher scores in the case group for depressive symptoms (p < 0.01) and state anxiety (p < 0.01). These symptoms ameliorated over time in the case group. At baseline, cases showed higher concentrations of CD177⁺ EVs compared to controls (p = 0.02). Among T cell-derived EVs, CD4⁺ vesicles were significantly more abundant in cases than controls at follow-up (p = 0.04). At baseline maternal functioning was inversely associated with several EV subtypes. Finally, the treatment of zebrafish embryos with baseline EVs of cases with low level of anxiety resulted in a significant increase in neutrophil recruitment. This study suggests the existence of a complex interplay between stressful events, maternal mental health and innate immune modulation of infants with an acute infectious disease. New studies are needed to confirm the results of the present research.

Human reward processing varies along cue-centric and outcome-centric axes, but the mechanistic basis of individual variation in incentive salience attribution remains incompletely characterized. Here we show, using fMRI across five cohorts (N-total = 1251; N1 = 890; N2 = 245; N3 = 34; N4 = 48; N5 = 34), two reproducible imaging phenotypes mirroring sign- and goal-tracking (ST-like, GT-like). ST-like individuals showed dominant ventral striatal responses to reward-anticipation cues and sustained incentive salience attribution; GT-like individuals showed heightened responses to reward outcomes. This distinction was replicable across sites and independent samples. Single-dose and repeated-dose D₂/D₃ antagonism (risperidone, haloperidol, amisulpride) selectively reduced anticipatory ventral striatal activity in ST, with single-dose antagonism additionally producing a parallel drop in self-reported energy. Instead, D₂/D₃ partial agonism (aripiprazole) increased anticipatory and reduced outcome-phase responses in GT. In a psychosis cohort, antipsychotic D₂ affinity was associated with blunted anticipatory signals and higher negative symptom burden, offering a neuroimaging-driven basis for stratifying patients and predicting response to dopaminergic agents.

This study aimed to systematically assess the burden and temporal patterns of vision impairment due to diabetes mellitus (DM), including moderate vision loss (MVL), severe vision loss (SVL), and blindness, and to identify the demographic drivers of future changes.

An age-period-cohort (APC) model was used to evaluate the effects of age, period, and birth cohort on diabetes-related vision impairment, with analyses stratified by diabetes type, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Decomposition analysis was further conducted to quantify the relative contributions of population aging, population growth, and epidemiological changes to projected changes in prevalent case numbers through 2030.

the age-standardized prevalence rates (ASPRs) of blindness due to type 1 diabetes mellitus (T1DM) continued to rise [males: average annual percentage change (AAPC) = 0.82% (95%CI 0.40-1.23); females: AAPC = 1.31% (95%CI 0.86-1.77)]. The age effect indicated that older populations were at higher risk. Meanwhile, the cohort effect revealed that in regions with high Sociodemographic Index (SDI), high-middle SDI, and middle SDI, later-born cohorts had a significantly higher risk of diabetes-related vision impairment compared to earlier-born cohorts. Globally and in most regions, population growth was the main driver of increased in the number of prevalent MVL and SVL cases, whereas epidemiological change contributed most to increases in prevalent blindness cases. However, population aging had a particularly substantial impact in East Asia, High-income Asia Pacific, Central Europe, Eastern Europe, and Western Europe.

The global burden of vision impairment due to DM increased continuously. Older populations represented high-risk groups, and the burden varied by sex, diabetes type, and socioeconomic development, with T2DM contributing most to the overall increase in diabetes-related vision impairment. Although population growth and epidemiological changes were major contributors, the impact of population aging in certain regions was also noteworthy.

Chronic stress (CS) acts as both an initiating and aggravating factor for depression and osteoporosis. Cumulative evidence indicates that Cathepsin K (Cat K), a cysteine protease, is functionally linked to chronic stress and exerts critical regulatory roles in bone metabolism. Nevertheless, the molecular mechanisms whereby CS promotes osteoporosis in the background of mood-related disturbances remain poorly defined. In the present work, we established a combined mouse model of osteoporosis and chronic stress. We evaluated anxiety- and depression-like behaviors, the expression profiles of Cat K, autophagy-, apoptosis-, and inflammation-associated proteins in bone tissue, as well as vascular senescence in experimental animals. Furthermore, we investigated the biological effects of serum collected from chronically-stressed mice on MC3T3-E1 osteoblast-like cells. Following 8-week chronic stress exposure, ovariectomized (OVX) mice developed prominent anxiety- and depression-like behaviors, accompanied by deteriorated osteoporosis and aortic senescence. Meanwhile, bone tissues exhibited elevated levels of Cat K, p62, pro-inflammatory mediators, and apoptosis-related proteins, whereas the autophagy marker LC3B/A was down-regulated. Administration of E64d, a cysteine protease inhibitor, markedly reversed these pathological alterations. In vitro culture revealed that serum from chronically-stressed mice suppressed the viability of MC3T3-E1 osteoblast-like cells. Pharmacological inhibition of Cat K restored autophagic activity, mitigated the overexpression of pro-inflammatory and pro-apoptotic mediators, and rescued MC3T3-E1 cells from stress-triggered injury. Collectively, our findings demonstrate that chronic stress induces anxiety- and depression-like phenotypes in OVX mice and accelerates bone loss, at least partially via Cat K activation and autophagy suppression.

Non-communicable diseases (NCDs) are rising rapidly in Sub-Saharan Africa. In Guinea-Bissau, nationwide data are scarce. We aimed to estimate the multi-regional prevalence of type 2 diabetes (T2D), obesity, and hypertension and examine associated risk factors within this resource-limited context.

A multi-regional cross-sectional survey was conducted using a hybrid community- and facility-based sampling approach across urban Bissau, including at the National Diabetes Clinic [CND] and in seven interior regions of the country. Recruitment was conducted between August 3th 2022 and June 8th 2024 across these sites. After a verified 12-h fast, participants underwent capillary glucose, blood pressure, and anthropometric measurements. Diabetes was defined as fasting glucose ≥ 126 mg/dL or previous diagnosis; prediabetes as 110-125 mg/dL; obesity as BMI ≥ 30 kg/m²; and hypertension as blood pressure ≥ 140/90 mmHg. Multivariable logistic regression identified factors associated with diabetes.

Among 3929 participants, with median age 41 years, the overall raw diabetes prevalence was 20.8% (817/3929), with 30% being newly screen-detected. The T2D prevalence at the specialized CND was 22.8% (342/1502), compared to 18.0% (174/969) in community settings outside health facilities in Bissau. The prediabetes prevalence was 9.1%; while the obesity prevalence was 14.8%, disproportionately affecting more women, at 20.7% vs. 9.1% in men; and the prevalence of hypertension was exceptionally high at 40.4%. In the multivariable model, key risk drivers included age ≥ 55 years (OR 14.0, 95% CI: 8.57-22.9), family history (OR 3.78, 3.02-4.74), Fula ethnicity (OR 2.47, 1.73-3.53), and low physical activity (OR 1.44, 1.17-1.78).

Guinea-Bissau faces a critical, underreported burden of metabolic and cardiovascular NCDs, particularly T2D and hypertension. Given the recruitment pathways, the overall prevalence reflects a high-risk baseline that warrants cautious national extrapolation. Urgent, context-specific public health strategies and decentralized clinical guidelines are required to manage these chronic conditions amidst severe structural resource constraints.