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Whole-brain cortical morphometry and structural covariance network disruption in subacute sclerosing panencephalitis.1 week agoSubacute sclerosing panencephalitis (SSPE) is a progressive, fatal encephalitis caused by persistent measles virus infection. Quantitative cortical imaging in SSPE remains poorly characterised, and the topology of the cortical structural covariance network (SCN) has not been examined.
To characterise whole-brain cortical structural alterations in SSPE using surface-based morphometry (SBM) and voxel-based morphometry (VBM), evaluate their clinical correlates, and describe the topology of the cortical SCN.
Twenty-eight patients with SSPE and 48 age- and sex-matched healthy controls underwent 3.0 T volumetric T1-weighted MRI. SBM was performed in FreeSurfer using the Desikan-Killiany (DK) atlas, adjusted for age and sex; VBM used the FSL-VBM pipeline with threshold-free cluster enhancement, adjusted for age, sex and total intracranial volume. Clinical associations used Pearson correlation with false discovery rate (FDR) correction and Spearman sensitivity analyses; severity was quantified with the Neurological Disability Index. Group-level SCNs were constructed from age- and sex-adjusted regional thickness correlations; graph metrics were computed across 16 network densities and summarised as the area under the metric-versus-density curve, so that findings do not depend on a single arbitrary threshold. Group differences were assessed by subject-label permutation testing with bootstrap confidence intervals.
VBM identified widespread bilateral grey matter volume reduction extending from cortex into deep grey matter and cerebellum, with additional right-lateralised clusters in the planum temporale and frontal pole. Vertex-wise SBM demonstrated 35 bilateral cortical thickness clusters and 21 cortical volume clusters; in the covariate-adjusted regional analysis, 38 of 68 DK regions showed significant thinning after FDR correction, and 18 of 68 regions showed significant volume reduction, most prominently the bilateral frontal pole and posterior cortices. Cortical thickness and volume correlated negatively with disease duration across most regions, but not with clinical severity. SCN metrics differed consistently in direction across all densities - longer characteristic path length, higher modularity and local efficiency, and loss of degree assortativity in patients - but no metric difference survived subject-label permutation testing after FDR correction (smallest adjusted p = 0.24); SCN findings are therefore reported as descriptive.
SSPE produces widespread, duration-dependent cortical thinning and grey matter volume loss involving association, limbic and primary cortices. Group-level SCN topology showed a consistent directional pattern of network reorganisation that did not reach corrected statistical significance at this sample size. Prospective, longitudinal and multi-centre studies are required before any clinical application of these measures can be considered.Mental HealthCare/Management -
Physical Activity for Youth Mental Health in the "Online Era": Risks, Opportunities, and Implementation Priorities.1 week agoToday's young people (aged ∼10-24 y) are the first "digital natives" but have become the most sedentary generation on record. These trends have coincided with a widely recognized decline in youth mental health, prompting increasingly polarized debate: some attribute the crisis primarily to smartphones and social media, but large-scale analyses suggest more heterogeneous population-level effects. Therefore, this review examines the role of physical activity (PA) in mental health during the online era; considering how different forms of online engagement relate to youth mental health, with regard to both the emerging downsides (through increasing sedentariness) and the potential for harnessing such platforms to improve PA and mental health, together. As a narrative review of an emerging field, we drew on nonsystematic searches of PubMed and Google Scholar alongside author expertise to integrate key findings and identify new directions. Two conclusions emerged. First, whether online time helps or harms depends more on content, context, and user characteristics than screentime, although converging (though still-developing) causal evidence points to displacement of PA, alongside disrupted sleep as a leading mechanism. Second, digital adoption itself has become an opportunity for promoting PA/delivering exercise interventions, online, with growing evidence of benefits for depression, anxiety, and well-being. However, these tools also carry risks, including body surveillance, social comparison, and compulsive exercise. Furthermore, data on online PA interventions in clinical mental health populations is sparse but appear to favor blended approaches. Overall, we argue the coming decade's key challenge is embedding evidence-based PA promotion within young people's online lives.Mental HealthCare/Management
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Choroid plexus enlargement in Post-COVID-19 syndrome is linked to Serum-Induced cytokine secretion in human hippocampal progenitors.1 week agoPost-COVID-19 syndrome (PCS) is characterised by persistent cognitive, affective, and somatic symptoms that extend months beyond acute SARS-CoV-2 infection, frequently in the absence of overt systemic inflammation. While immune dysregulation is increasingly implicated, the mechanisms linking peripheral immune alterations to enduring brain-related symptoms remain poorly understood. The choroid plexus (CP), a specialised blood-cerebrospinal fluid barrier and neuroimmune interface, is well positioned to mediate such immune-brain communication.
In this pilot case-control study, we combined high-resolution structural MRI with peripheral immunophenotyping and a functional human neural progenitor model to investigate the neuroimmune relevance of CP morphology in PCS. Twenty individuals with PCS following mild acute COVID-19 and twenty recovered controls underwent MRI for manual CP segmentation, serum cytokine profiling, and serum exposure assays using human hippocampal progenitor cells.
Individuals with PCS exhibited significantly enlarged CP volume compared with recovered controls, independent of intracranial volume. CP enlargement showed minimal association with circulating cytokine concentrations, indicating limited correspondence with contemporaneous peripheral inflammatory markers. In contrast, CP volume was tentatively associated with serum-induced immune and astrocytic responses in vitro, including reduced IL-8 sretion and altered astrocytic marker expression (GFAP and AQP4), while no associations were observed with neuronal differentiation markers.
These findings highlight a dissociation between static peripheral cytokine levels and functional brain-relevant immune effects, and suggest that CP enlargement preferentially indexes brain-proximal neuroimmune signalling capacity rather than peripheral inflammatory load alone. By integrating neuroimaging with human cellular assays, this study positions the choroid plexus as a structural marker of persistent neuroimmune dysregulation in PCS and highlights immune-barrier interfaces as critical targets for understanding post-infectious brain symptoms.Mental HealthCare/Management -
40 Hz Transcutaneous Auricular Vagus Nerve Stimulation Enhances Verbal Free Recall in Healthy Adults by Modulating Frontal Theta Oscillations.1 week agoTranscutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation approach that may influence memory-related brain activity. Theta oscillations are closely related to episodic memory processing, but it remains unclear whether taVNS modulates memory-related theta activity in a frequency-specific manner and how these effects change after stimulation.
This study investigated the sustained effects of 20 Hz and 40 Hz taVNS on free recall and resting-state EEG theta oscillations in healthy young adults.
Forty-four participants were enrolled in this randomized, single-blind, sham-controlled, three-arm parallel-group study. They were randomly assigned to the sham stimulation group, the 20 Hz taVNS group, or the 40 Hz taVNS group. Free recall performance was assessed before and after stimulation, and resting-state EEG was recorded at baseline and multiple time points after stimulation.
The results showed that participants receiving 40 Hz taVNS exhibited better free recall performance than those receiving sham stimulation or 20 Hz stimulation. 40 Hz taVNS increased the relative power of theta waves, particularly in the frontal region. This enhancement was an immediate increase followed by a gradual decrease over time. Frontal theta activity and stimulation-induced theta changes were positively correlated with free recall performance. Furthermore, exploratory Bayesian mediation analysis supported a theta-dependent model.
This study suggests that 40 Hz taVNS may promote verbal free recall performance by inducing transient enhancement of frontal theta wave activity, providing preliminary evidence for the modulation of memory-related neural oscillations by frequency-specific taVNS.Mental HealthCare/Management -
The impact of behavioural activity on the EEG power spectrum, its source localisation, and global functional connectivity in rats Behavioural modulation of rat EEG dynamics.1 week agoThe behavioural activity of freely moving animals is a confounding factor that affects the recording, analysis, and final results of animal EEG experiments. Along with the lack of standardisation in animal in vivo electrophysiology experiments, this could lead to huge inconsistencies, especially in the analysis of centrally acting drugs. Therefore, the main aim of this paper is to investigate the effects of behavioural activity versus inactivity on the multichannel EEG in freely moving rats. In a large sample (n = 116) of waking recordings from 12 cortical electrodes (ECoG) in Wistar rats, we evaluated behavioural activity-related changes in the power spectrum, current source density, and power-based global functional connectivity (GFC) in a 3D rat brain model, according to the TOHOKU Rat Brain Atlas. The main findings were that behavioural activity was associated with 1) a robust power increase in 6-8 Hz, peaking at 7 Hz with maximum changes over the parietal and temporal cortex, 2) an increase in gamma (30-40 Hz) and high-gamma (55-100 Hz) power across the whole brain, 3) a decrease in delta (1-4 Hz) and beta (12-25 Hz) and high-beta (25-30 Hz) power across the whole cortex. Changes were also localised in subcortical regions, particularly in the diencephalon/thalamus. The GFC analysis showed a similar pattern of changes across the 6-8 Hz, delta, and beta bands; however, GFC in the gamma band decreased, while high-gamma GFC increased. Again, the GFC analysis revealed changes in connectivity within subcortical structures, primarily in the thalamus. None of the measures was affected in the alpha band (8-12 Hz). These findings emphasise behavioural state as a critical factor influencing EEG outcomes, with important implications for the standardisation and translational validity of preclinical neurophysiological studies.Mental HealthCare/Management
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Proteins from platelet-enriched preparations as candidate biomarkers for major depressive disorder: An exploratory proteomic study.1 week agoMajor depressive disorder (MDD) is a complex psychiatric disorder lacking objective clinical diagnostic biomarkers. Platelets express a variety of neuroactive proteins, including serotonin transporters and receptors, and are easily accessible in peripheral blood, making them a valuable surrogate tool for exploring molecular alterations underlying central nervous system diseases. This study aimed to screen proteins from platelet-enriched preparations as candidate biomarkers for distinguishing patients with MDD from healthy controls (HCs) and to preliminarily explore the potential biological mechanisms of platelets in MDD pathogenesis. A total of 20 patients with MDD and 20 age- and gender-matched HCs were enrolled. Data-independent acquisition (DIA)-based proteomic analysis identified 299 differentially expressed proteins in the platelet-enriched fraction between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to characterize the functional profiles and signaling pathways of these altered proteins. Multiple machine-learning algorithms, including PLS-DA, LASSO regression, and SVM-RFE, were applied to screen optimal biomarker combinations. Finally, a four-protein panel consisting of C1QBP, DDX60, WDR81, and VPS37A showed favorable discriminatory potential for MDD, with consistent expression trends further examined in the validation cohort. The expression levels of this biomarker panel were correlated with HAMD scores in the pooled sample, which primarily reflected case-control differences. Within the MDD group, only C1QBP was significantly correlated with HAMD scores, whereas no significant correlations were observed for the other candidate proteins. Exploratory gender-stratified analysis further suggested potential gender-based heterogeneity in protein profiles of the platelet-enriched fraction among MDD individuals. In conclusion, this exploratory proteomic study identifies C1QBP, DDX60, WDR81, and VPS37A as potential candidate biomarkers from platelet-enriched preparations for MDD discrimination.Mental HealthCare/Management
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Effects of Repeated Ketamine Infusions on Suicidal Ideation in Treatment-Resistant Depression and Associated Changes in Selected Plasma Biomarkers.1 week agoThis study investigated the antisuicidal effects of repeated intravenous ketamine in patients with treatment-resistant depression and explored associations between suicidal ideation and temporal changes in selected plasma biomarkers to identify potential biomarkers.
This secondary analysis of an open-label trial included outpatients with treatment-resistant depression who received four intravenous ketamine infusions (0.5 mg/kg) over 2 weeks. Suicidal ideation was assessed at baseline and post-intervention using the Montgomery-Åsberg Depression Rating Scale (item 10), Quick Inventory of Depressive Symptomatology-Self Report (item 12), and Columbia Suicide Severity Rating Scale. Eleven targeted plasma biomarkers were quantified via liquid chromatography-mass spectrometry. Associations between suicidal ideation scores and biomarker changes were evaluated using Pearson's and Spearman's correlation coefficients, with p-values adjusted for multiple comparisons using the false discovery rate procedure.
Repeated ketamine infusions were associated with modest reductions in suicide-related item scores on the Montgomery-Åsberg Depression Rating Scale item 10 (1.5±1.5 to 1.0±1.3, p=0.01) and Quick Inventory of Depressive Symptomatology-Self Report item 12 (1.3±0.9 to 0.8±0.9, p=0.01). Columbia Suicide Severity Rating Scale scores numerically decreased (1.1±1.3 to 0.8±1.2, p=0.17) without reaching statistical significance. In unadjusted analyses, improved Columbia Suicide Severity Rating Scale scores showed nominal associations with increased levels of citric acid (r=- 0.40, p=0.03) and kynurenic acid (ρ=- 0.37, p=0.04), although these did not survive false discovery rate correction.
Repeated ketamine infusions were associated with modest reductions in suicide-related item scores on the Montgomery-Åsberg Depression Rating Scale and Quick Inventory of Depressive Symptomatology-Self Report. While no definitive biomarkers were identified after false discovery rate correction, these nominal associations are purely hypothesis-generating and require larger validation trials.Mental HealthCare/Management -
Generative artificial intelligence and commercial sexual exploitation of children: Implications for healthcare providers.1 week agoGenerative artificial intelligence (GAI) has created new avenues for the commercial sexual exploitation of children through the creation or manipulation of sexually explicit images using a child's likeness. Such images constitute a form of child sexual abuse material (CSAM), including when they are generated or manipulated without physical contact with the child. Because this abuse may occur without the child's awareness, it can complicate recognition, disclosure, and intervention while contributing to ongoing psychological harm. When such content is produced, distributed, or monetized in exchange for anything of value, it may also constitute commercial sexual exploitation of children (CSEC), a term commonly used to describe child sex trafficking. Healthcare providers play an important role in identifying possible GAI child sexual abuse material (GAI-CSAM), supporting affected children and caregivers, and incorporating digital safety into routine care. This article highlights clinical considerations for pediatric, primary care, and mental health settings, including developmentally appropriate assessment of online experiences, caregiver education, trauma-informed response, and multidisciplinary collaboration. As generative technologies evolve, clinician awareness is essential to strengthen prevention, early intervention, and responses to technology-facilitated exploitation.Mental HealthCare/Management
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Relationships between PTSD symptom clusters and firearm storage and carrying practices among veterans.1 week agoFirearm suicide is highly prevalent among U.S. veterans. Research suggests that firearm ownership and unsecure firearm storage elevate risk, both of which are common among veterans. Posttraumatic stress disorder (PTSD) may contribute to both suicide risk and unsecure storage, yet research examining PTSD symptom clusters and firearm storage practices remains limited.
Veterans (n = 145) who owned a firearm or lived in a home with a firearm were recruited from an outpatient VA mental health clinic. Participants completed the PTSD Checklist for DSM-5 (PCL-5) which provides subscale scores for intrusion, avoidance, changes in cognition and mood, and arousal symptoms. Veterans were also assessed for unsecure firearm storage and carrying practices. Logistic regressions were conducted to examine the associations between PCL-5 symptom clusters and four discrete firearm storage or carrying behaviors.
PCL-5 arousal symptoms were associated with increased odds of storing firearms unlocked (OR = 1.164, 95% CI [1.045-1.297], p = .006). PCL-5 avoidance symptoms were associated with decreased odds of carrying a loaded firearm (OR = 0.676, 95% CI [0.488, 0.935], p = .018).
Findings highlight that specific PTSD symptom clusters are associated with discrete firearm storage and carrying behaviors. These results may inform more precise lethal means counseling approaches for veterans with PTSD and contribute to broader efforts to develop more tailored and effective suicide prevention interventions for this vulnerable population.Mental HealthCare/Management -
Engagement as a predictor of suicidal ideation and suicide attempts: Evidence from a 12-month ecological momentary assessment study in psychiatric outpatients.1 week agoEcological momentary assessment (EMA) enables real-time monitoring of suicidal thoughts, offering a window into dynamic risk processes that static assessments miss. However, it remains unclear whether patterns of EMA engagement-rather than the content of responses-carry clinical significance for suicide risk. This year-long prospective cohort study examined whether EMA engagement predicted daily suicidal ideation and clinician-assessed suicide attempts during the 12-month period among psychiatric outpatients at elevated suicide risk. Participants (N = 585; M age = 44.1 years, SD = 14.4; 64.4% female) completed daily EMAs via the MEmind mobile application. Engagement was indexed by (1) total EMA responses and (2) EMA consistency, defined as the cumulative proportion of days with at least one EMA completed. Mixed-effects models estimated associations between engagement and (a) daily active and passive suicidal ideation and (b) suicide attempts obtained from electronic health records. Quadratic models revealed an inverted-U relationship between EMA consistency and active ideation (β2 = -185.55, p = .035). Higher EMA consistency predicted a lower likelihood of a suicide attempt (aOR = 0.72, p = .038), and this protective effect followed a nonlinear pattern (β2 = -10.75, p = .031). Consistent EMA engagement was associated with reduced suicide-attempt risk, independent of demographic factors. Engagement itself, beyond self-reported ideation, may serve as a behavioral marker of suicidality.Mental HealthCare/Management