The central vein sign (CVS) and the paramagnetic rim lesion (PRL) are neuroimaging biomarkers of multiple sclerosis (MS).

To determine the diagnostic performance of CVS and PRL integration in people presenting for initial diagnostic evaluation of MS.

Adults with clinical/radiological suspicion of MS, aged 18-65, with CVS and PRL assessment from the CentrAl Vein Sign in MS (CAVS-MS) pilot were included. Diagnostic performance of CVS and PRL combinations was evaluated, with 2017 McDonald criteria as the reference standard.

Seventy-eight participants were included (71% female, 86% white, 37 with MS). The combination of ⩾1 CVS and ⩾1 PRL demonstrated sensitivity/specificity of 0.76 (95% CI, 0.59, 0.88) and 0.93 (95% CI, 0.80, 0.98). The combination of ⩾6 CVS and ⩾1 PRL demonstrated sensitivity/specificity of 0.57 (95% CI, 0.39, 0.73) and 1.00 (95% CI, 0.91, 1.00). In those with cerebrospinal fluid testing (n = 46, 24 with MS), ⩾6 CVS and ⩾1 PRL diagnostic specificity was 1.00 (95% CI, 0.85, 1.00), similar to that of oligoclonal bands and dissemination in space by magnetic resonance imaging (0.82 [95% CI, 0.60, 0.95]).

Integrating CVS and PRL represents potentially advantageous MS diagnostic biomarkers, with increased specificity and without substantial reduction in sensitivity.

Overdoses of extended-release (ER) medications can cause life-threatening toxicity from prolonged gastrointestinal drug retention due to pharmacobezoar formation. This may result in severe complications including delayed serotonin syndrome and intestinal ischemia despite early use of enhanced elimination strategies.

A 45-year-old woman presented with altered mental status following carbamazepine-venlafaxine ER overdose. Initial carbamazepine concentration was 163 μmol/L. She suffered a ventricular tachycardia arrest requiring venoarterial extracorporeal membrane oxygenation and enhanced elimination with continuous renal replacement therapy (CRRT). After CRRT, carbamazepine concentration rebounded from 33 to 80 μmol/L and clinical features of serotonin syndrome developed suggesting ongoing absorption. CT revealed cecal pneumatosis with obstruction. Laparotomy at day 9 revealed transmural ischemic necrosis with 4-6 L of retained charcoal and polyethylene glycol mixture; source control required a right hemicolectomy. Carbamazepine concentration declined postoperatively and serotonergic symptoms resolved.

Carbamazepine-venlafaxine ER overdose with retained pill fragments can cause a variety of complications including prolonged toxicity. Rebounding drug concentration following enhanced elimination should trigger an investigation for gastrointestinal sequestration and prompt surgical consultation.

Emotion regulation relies on the interplay between prefrontal and limbic brain regions, with prefrontal regions implicated in the top-down modulation of the amygdala. In social anxiety disorder, disruptions in these networks have been reported, but most studies used undirected functional connectivity.

Dynamic causal modelling (DCM) was used to assess effective (i.e. directed) connectivity differences during emotion processing and regulation in individuals with social anxiety disorder compared with healthy controls.

A total of 102 participants (61 with social anxiety disorder, 41 healthy controls) performed a functional magnetic resonance imaging emotion regulation task under two conditions: viewing neutral/negative faces, and downregulating emotions using a self-chosen strategy. DCM was applied to model effective connectivity among the amygdala and key prefrontal regions. Connectivity patterns were characterised in healthy controls, and group comparisons tested how social anxiety disorder differed from this baseline model using parametric empirical Bayes. Leave-one-out cross-validation (LOOCV) evaluated whether connectivity differences predicted diagnostic group, symptom severity and emotion regulation difficulties.

In healthy controls, observation of negative faces was characterised by reciprocal influences between the amygdala and prefrontal cortex (PFC), including increased amygdala-to-ventromedial PFC (vmPFC) connectivity and inhibitory vmPFC-to-amygdala connectivity. During emotion regulation, healthy controls showed negative modulation from the amygdala to all prefrontal regions. Patients with social anxiety disorder did not differ from controls in amygdala-prefrontal connectivity; their alterations were confined to prefrontal circuits, with inhibitory connectivity from the pre-supplementary motor area (preSMA) to dorsolateral PFC during observation and bidirectional excitatory connectivity between the preSMA and vmPFC during regulation. LOOCV indicated that connectivity differences predicted diagnostic group.

The results support the idea that emotion processing and regulation influence connectivity between prefrontal areas and the amygdala in a complex, feedback-driven manner. Our findings suggest that aberrant emotion regulation in social anxiety disorder appears to be more closely linked to differences in intra-prefrontal circuits than deficits in amygdala-prefrontal connectivity.

People with intellectual disability experience substantial health inequities, including higher multimorbidity, increased healthcare utilisation and markedly reduced life expectancy. High-quality research is essential to address these disparities. The National Institute for Health and Care Research (NIHR) funded Research Delivery Network provides the infrastructure/expertise/support needed to deliver NIHR-funded studies, and supports studies funded by a non-commercial/industry partner. However, the effectiveness of NIHR-funded studies versus those supported in driving impactful intellectual disability research remains unclear.

To evaluate and compare the outcomes of NIHR-funded and supported intellectual disability research.

All NIHR studies (funded/supported) relating to intellectual disability (2010-2020) were identified through systematic register searches. Primary outcomes included publication rates and impact on local, national and international clinical guidelines. Data collection was supplemented with a questionnaire to chief investigators and literature searches. Quantitative analyses examined associations between funding status, study design, publication and guideline impact, whereas qualitative responses explored implementation challenges.

In total, 88 projects were identified, and 42% (37/88) were NIHR-funded. Overall, 81% of studies generated at least one publication and 28% informed clinical guidelines. NIHR funding was not significantly associated with publication or guideline impact. Randomised controlled trials (RCTs) were significantly more likely to be published and more likely to influence non-UK national and international guidelines than non-RCTs. The amount of funding showed no association with impact. Qualitative findings highlighted funding constraints, staff capacity and stakeholder engagement as key determinants of implementation.

NIHR-funded intellectual disability research was no more likely than NIHR-supported studies to result in publications or guideline impact.

Many mental disorders show strong genetic influence. In parallel, dynamic functional network connectivity (dFNC) has shown high sensitivity to brain changes related to mental disorders. However, previous studies linking dFNC to genetics largely follow a paradigm to identify associations between one set of genetic factors and multiple sets of connectivity features from different dFNC states, ignoring the potential variability in genetic correlates across states. We propose a novel joint ICA (jICA)-based "dynamic fusion" framework to identify dynamically tuned genetic manifolds. A sliding window approach was utilized to estimate four dFNC states and compute subject-level state-average dFNC (sa-dFNC) features. The sa-dFNC features of each state were combined with schizophrenia risk single nucleotide polymorphisms (SNPs) within a jICA fusion framework, resulting in four parallel fusions in 32,861 individuals of the UK Biobank cohort. The extracted four sets of joint SNP-dFNC components were further validated for clinical relevance in a combined schizophrenia cohort of 820 individuals (348 patients). The similarity of SNP-dFNC components across four parallel fusions was evaluated as a measure of state variability. We observed a mixture of "state-invariant" and "state-variant" components for SNP and dFNC modalities. Particularly, the schizophrenia-related state-variant SNP components, or manifolds, complemented each other by capturing different SNPs involved in the same biological functions, revealing a partition of genomic risk particularly elicited by the dynamics of brain function. By augmenting the SNP factors to state-variant manifolds, this dynamic fusion framework promises additional insights into the underlying genetic risk of disease-related alterations in dynamic brain function.

Athletes frequently experience potentially traumatic events related to sports injuries, significantly increasing their risk of developing post-traumatic stress disorder (PTSD). However, existing assessment methods often overlook the heterogeneity of symptom presentation and the necessity for individualized mental health management. Furthermore, exploration of mental health support for the specific population of student-athletes remains limited. This study aims to integrate a deep learning-driven clustering paradigm with a stratified care framework to explore distinct PTSD symptom clustering profiles among high-performance college athletes who have experienced severe sports injuries.

A total of 468 high-performance college athletes who had sustained severe sports injuries within the past year were recruited to complete the PCL-C questionnaire. Transformer-based semantic embedding techniques were used to encode PTSD symptom data, followed by Principal Component Analysis (PCA) and K-means clustering to extract latent subgroups. Model performance was compared with traditional clustering approaches to evaluate clustering validity and representational quality.

Deep learning-based semantic clustering paradigms demonstrate efficacy and feasibility in capturing symptom distributions and latent heterogeneous combinations of clustered symptoms. Five distinct PTSD clusters were identified, reflecting a continuous gradient of symptom severity and heterogeneous combinations of intrusive, avoidance, emotional numbness and hyperarousal features. These clusters correspond to varying levels of clinical risk and offer a complementary insights for stratified care and mental support.

This study proposes a novel cluster-based research paradigm for the precise screening of PTSD in student-athletes. By integrating clustered symptom profiles with stratified care principles, the findings provide actionable insights for optimizing resource allocation and enhancing mental health support systems for student-athletes.

Fatty acid-binding protein 7 (FABP7) assists in the intracellular trafficking of endogenous cannabinoids and polyunsaturated fatty acids (PUFAs) and has been implicated for various psychiatric diseases. Rising evidence demonstrates the crosstalk between the endocannabinoid and dopaminergic systems, particularly in response to stress. The present study seeks to examine the role of FABP7 expression under chronic stress conditions and its impact on the dopaminergic system, specifically dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) levels. Adult male FABP7^+/+ and FABP7^-/- mice underwent 28-day treatment of unpredictable chronic mild stress (UCMS) procedure. After the stress paradigm, D1R and D2R levels were measured with in vitro autoradiography using [³H] SCH23390 and [³H] Spiperone, respectively. Stressed mice, regardless of genotype, exhibited an increase in D1R binding across the entire striatum (dorsal caudate putamen (CPu), dorsolateral CPu, dorsomedial CPu, ventral CPu, ventrolateral CPu, ventromedial CPu, nucleus accumbens core and shell), substantia nigra and olfactory tract. Additionally, an increase in D2R binding induced by UCMS was observed in the olfactory tract and certain regions of the striatum (dorsal CPu and ventral CPu). The UCMS paradigm upregulates D1R and D2R binding independent of FABP7 gene deletion, suggesting a compensatory role of other FABPs in the brain in maintaining dopaminergic homeostasis. This stress-induced shift in D1R: D2R ratio may underlie the pathogenesis of major depressive disorder and substance use disorder, as well as the high comorbidity among these conditions.

Despite its serious impact, anorexia nervosa (AN) remains one of the least understood mental illnesses, with significant gaps in effective treatment options. No medications have been deemed effective and only 50% of individuals respond to conventional psychotherapies. Gastrointestinal (GI) bacteria have been found to be altered in individuals with AN. While, Fecal microbiota transplantation (FMT) has shown potential for alleviating anxiety and depression, its effects remain understudied for individuals with AN. This study aims to determine whether oral capsular FMT is acceptable to adolescents with AN and results in clinical improvement in weight and/or psychological symptoms.

This study will randomise 20 adolescents with AN, ages 12-17 years, to receive either FMT or placebo capsules. These 20 youth, as well as an additional 10 youth who decline trial enrolment, will participate in qualitative interviews. We will track recruitment rates and collect psychological and biological measures (blood, stool, urine and saliva) at multiple timepoints to assess how gut microbiota and their metabolites may influence the symptoms of AN. Interviews with participants and caregivers will explore their experiences and views on FMT as a treatment approach.

This study has received ethics approval by the Hamilton Integrated Research Ethics Board (#17493) and investigational drug approval by Health Canada (Dossier ID: c292423). Informed consent will be obtained by research staff from all participants. Findings will be disseminated through academic conferences, clinical forums and partnerships with advocacy organisations to reach clinicians, researchers and individuals with lived experience.

NCT06593366.

Mental health disorders (MHDs) remain a leading cause of the global burden of diseases. Early identification of neurobiological mechanisms mediating a risk for MHDs is key to reducing a lifetime burden. Recent findings emphasize the locus coeruleus-norepinephrine (LC-NE) system as a neuromodulator of arousal translating acute stress responses into neuronal excitability. We propose that individual differences in LC-NE functioning can explain a differential susceptibility to psychological adversity, which mediates the development of transdiagnostic psychopathology in early childhood.

The primary objective of LOCUS-MENTAL is to assess LC-NE functioning in preschoolers as a predictor of later psychopathology. This will be applied to generate an objective tool of individual early risk prediction, supporting targeted prevention of MHD.

LOCUS-MENTAL includes 4 work packages. The centerpiece is an accelerated longitudinal study, in which a cohort of 300 preschool-aged children (aged 4-6 years) will be recruited and followed up across 3 assessment waves, each one year apart. This will characterize developmental trajectories from 4 to 8 years of age. The primary outcome is the prediction of transdiagnostic psychopathology by pupillometry-derived LC-NE functioning. Transdiagnostic psychopathology is assessed by the Child Behavior Checklist (CBCL), while LC-NE functioning is assessed with pupillometry that includes core metrics of baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR). Cross-lagged panel models will be applied to the longitudinal data for quantifying causal effects between LC-NE functioning, childhood adversity, and psychopathology. Normative modeling and classification approaches will estimate an individual risk prediction based on pupillometric metrics of LC-NE functioning. The pupillometric battery has 4 passive auditory and visual paradigms. This battery will be validated with a multitrait-multimethod design that combines pupillometry with neurophysiological measures in electroencephalography, behavioral and cognitive measures, and neurocognitive paradigms. The study was approved by the Ethics Committee of the Faculty of Medicine at Goethe University Hospital (2024-2160). Written informed consent will be obtained from caregivers and verbal assent by the children.

The study was funded in September 2024. Participant enrollment for the validation phase commenced in August 2025. As of February 2026, 82 participants were assessed, with a target of reaching 90 by the end of February 2026. Statistical analysis of the validation phase is planned for March 2026, with results aimed for publication in a peer-reviewed journal by the end of 2026. The longitudinal study is scheduled to start in April 2026 with completion in March 2029.

The LOCUS-MENTAL study will establish whether LC-NE functioning provides a validated biomarker for detecting early psychopathology. The associated pupillometry provides a feasible and scalable test for identifying high-risk developmental trajectories in preschool children, which can be translated to clinical practice. The resulting risk assessment tool could facilitate a shift toward objective screening for mental health risks that enables targeted prevention with evidence-based treatment before diagnosis onset. This could prevent sequential comorbidity and reduce the lifetime burden of MHDs.