Background Depression and anxiety are among the most prevalent mental health problems affecting university students and are associated with impaired academic performance, emotional distress and reduced quality of life. Cognitive behavioural therapy (CBT) is an evidence-based intervention that has demonstrated effectiveness in reducing symptoms of depression and anxiety; however, intervention-based studies among Indian university students remain limited. Purpose The present study aimed to evaluate the effectiveness of CBT in reducing symptoms of depression and anxiety among university students from medical, paramedical and non-medical academic streams. Methods A total of 600 university students were screened using the Depression Anxiety Stress Scale-21 (DASS-21). Of these, 180 students meeting the inclusion criteria and exhibiting mild to moderate symptoms of depression and/or anxiety were selected for the study. Participants were randomly assigned to a CBT intervention group ( n = 90) or a control group ( n = 90). The intervention group received an eight-session structured CBT programme, while the control group continued routine academic activities. Depression and anxiety levels were assessed before and after the intervention using the DASS-21. Data were analysed using repeated measures analysis of variance (RM-ANOVA). Results The CBT group demonstrated significant reductions in both depression and anxiety scores from pre-test to post-test, whereas the control group showed minimal change. RM-ANOVA revealed significant main effects of time and significant time × group interaction effects for both depression and anxiety ( p < .001), indicating that improvements were significantly greater among participants who received CBT. Conclusion The findings provide empirical evidence supporting the effectiveness of CBT in reducing depression and anxiety among university students. The results highlight the potential value of integrating structured CBT-based mental health interventions within higher education institutions to promote psychological well-being and academic functioning.
OBJECTIVE:Memory impairment is a frequent comorbidity of focal epilepsy, incompletely explained by seizure frequency or structural pathology. Ictal and postictal hippocampal dysfunction disrupt memory processes, but their cumulative impact remains poorly quantified. This study introduces cumulative hippocampal seizure-related burden metrics and examines their association with long-term memory consolidation. METHODS:A total of 20 consecutive patients undergoing stereo-electroencephalography in Marseille (2016-2018) were prospectively included. Continuous stereo-electroencephalogram recordings between 2 memory assessments (30 minutes and 1 week postencoding) were analyzed. Hippocampal ictal involvement and durations were assessed using epileptogenicity markers and visual stereo-electroencephalogram analysis. The postictal period was quantified using permutation entropy. Cumulative hippocampal seizure-related burden metrics (ictal, postictal, and combined) were computed across hippocampus-involving ictal events. Verbal and visual memory were assessed using standardized recall and recognition tasks. One-week performance was defined as the percentage score obtained at the 1-week assessment, whereas retention was defined as 1-week performance expressed as a percentage of 30-min performance. Associations were examined using univariate and multivariate analyses. RESULTS:Higher dominant-hemisphere hippocampal burden was associated with poorer 1-week verbal memory (performance and retention), independently of most covariates. Higher cumulative hippocampal seizure-related burden was associated with lower total recall performance (free + cued) and total recall retention (β = -25.04 and -23.88; R2 = 0.57 and 0.53; p < 0.05), and accounted for the greatest variance in both outcomes (adjusted R2 = 0.59 and 0.53; β = -25.45 and -24.27; p < 0.01), particularly when adjusting for epilepsy duration. No robust associations were observed between nondominant-hemisphere hippocampal seizure-related burden metrics and visual memory. Effects predominantly involved recall. INTERPRETATION:Cumulative ictal-postictal hippocampal dysfunction is a major predictor of impaired long-term verbal memory consolidation in focal epilepsy. ANN NEUROL 2026.
Background Traumatic brain injury (TBI) has an immense impact on families, particularly spouses, who face significant challenges such as changes in roles and responsibilities, relational dynamics and financial instability. The study aims to explore the psychosocial needs and concerns of couples coping with TBI from experts across various fields. Purpose The study purpose was to explore the psychosocial needs and concerns of couples coping with TBI from experts across various fields. Methods The current study adopted an exploratory qualitative approach, involving in-depth, face-to-face interviews with experts. Nine experts from six professional backgrounds were selected based on predefined inclusion and exclusion criteria. Eligibility criteria included a minimum of 5 years of expertise in TBI-related fields, proficiency in English and willingness to provide informed consent. The interviews were audio-recorded with the participants’ consent. Results Experts included neuropsychologists, psychiatric social workers, neurosurgeons, neuro-rehabilitation experts, physiotherapists and clinical nurses. A total of five themes have been identified, namely education needs, emotional needs, family needs, financial needs and support needs. Conclusion The study on the psychosocial needs of couples from experts’ perspectives in India is unique in nature. The results of this study will support the development and implementation of tailored psychosocial interventions specifically designed for couples in India. Various stakeholders engaged in the management of TBIs emphasised the critical importance of addressing the needs of these couples and ensuring the timely provision of personalised psychosocial support.
Background:COVID-19 has subacute as well as long-term effects defined as long COVID on multiple organ systems. Emerging literature suggests long-term effects of COVID-19 on the autonomic nervous system in survivors, the mechanistic basis of which is currently not delineated. Purpose:The study aimed to assess the cardiovascular autonomic functions in mild COVID-19 survivors and compare them with age- and sex-matched healthy controls. Methods:We recruited 34 young adult mild COVID-19 survivors. Autonomic function was assessed by cardiovascular autonomic reactivity tests at least 1 month after clinical recovery from acute COVID-19 infection. The responses were compared with those of 34 age- and sex-matched pre-COVID era healthy controls. Results:Mild COVID-19 survivors had significantly lower Valsalva ratio (1.578 ± 0.2747 vs 1.773 ± 0.3459; p = .0156) and displayed a greater fall in systolic blood pressure during head-up tilt test (-9.206 ± 7.121 vs 1.147 ± 8.457; p < .0001) in comparison to the healthy controls. Haemodynamic cardiovascular autonomic abnormalities were seen in 47% of COVID-19 survivors. Haemodynamic criteria of orthostatic hypotension were met in 12% of COVID-19 survivors, and postural orthostatic tachycardia syndrome haemodynamic criteria were met in 35% of COVID-19 survivors. Autonomic reflex responses to deep breathing, handgrip test and cold pressor test were found to be comparable between the two groups. Conclusion:Young adult mild COVID-19 survivors show lower cardiovagal and cardiovascular adrenergic responses to baroreflex-dependent autonomic reactivity as medium- to long-term autonomic sequelae. They have an intact non-baroreflex-dependent autonomic reactivity.
Background:Probiotic supplementation may influence mental health through the gut-brain axis, with potential effects on depression, anxiety, sleep, cognition, stress hormones, and gut microbial composition. This systematic review aimed to evaluate the effects of probiotics on psychological, physiological, and gut microbiome-related outcomes across diverse populations. Summary:A comprehensive search of PubMed, MEDLINE, PsycINFO, and ScienceDirect identified randomized controlled trials evaluating probiotic supplementation. Twenty RCTs were included, of which 15 were assessed as having a low risk of bias and five as having a high risk of bias. Commonly assessed outcomes included depression (n = 17), anxiety (n = 10), sleep quality (n = 9), stress (n = 6), cortisol (n = 7), cognitive function (n = 5), quality of life (n = 5), gut microbial composition (n = 11), and other neuroendocrine and inflammatory markers. Overall, probiotics were associated with improvements in depression, anxiety, sleep quality, mood, cognition, quality of life, and beneficial gut microbial populations, although findings for cortisol and stress-related outcomes were inconsistent. Key Message:Probiotic supplementation may provide beneficial effects on psychological well-being and gut microbial composition. However, heterogeneity among interventions, populations, outcome measures, and study quality warrants further well-designed RCTs.
Background:Internet addiction is increasingly conceptualised as a disturbance in affective and cognitive self-regulation rather than excessive use. Alexithymia, characterised by impaired emotional awareness, may heighten vulnerability by reducing the ability to identify and regulate emotions, thereby increasing the chances of indulging in maladaptive coping behaviours such as internet addiction. Purpose:The study aimed to examine the mechanism underlying alexithymia and internet addiction by investigating the mediating roles of psychological distress (affective dysregulation) and mindfulness (cognitive-regulatory capacity) in college students. Methods:A cross-sectional, quantitative research study was carried out among college students (n = 316) recruited from universities in the Gandhinagar district, Gujarat. Ethical clearance was obtained from the Institutional Ethics Committee for the study. Convenience sampling was employed to select the participants. College students between 18 and 25 years of age were included in the study. Data were collected using the Internet Addiction Test (IAT), Toronto Alexithymia Scale (TAS-20), General Health Questionnaire (GHQ-12) and Mindfulness Attention Awareness Scale (MAAS). SPSS, Version 22, and Hayes' PROCESS macro (Model 4) were used to carry out descriptive statistics, correlation and mediation analyses. Results:Alexithymia was positively associated with internet addiction (r = 0.35, p < .05), and negatively associated with mindfulness (r = -0.63, p < .01). Psychological distress was positively associated with internet addiction (r = 0.64, p < .05). The indirect effects of alexithymia on internet addiction were significant via psychological distress (B = 0.130, 95% CI [0.059, 0.204]) and mindfulness (B = 0.108, 95% CI [0.027, 0.186]). The mediation model accounted for 50% of the variance in internet addiction. The direct effect remained significant, indicating partial mediation. Conclusion:The findings supported parallel dual-regulatory pathways in which alexithymia was linked to internet addiction, with psychological distress and mindfulness serving as significant statistical pathways. These results indicated the relevance of integrated self-regulation frameworks in understanding behavioural addictions.
OBJECTIVE:Autoimmune encephalitis (AE) is associated with autoantibodies targeting distinct neuronal populations. In AE, antibodies against glutamate decarboxylase 65 (GAD65), expressed in GABAergic interneurons, are frequently detected. In GAD65-AE, hippocampal biopsies often show infiltrates of CD8+ cytotoxic T cells (CTLs), suggesting a prominent T cell-associated pathology. This has led to the hypothesis that CTLs contribute to neuronal injury in GABAergic circuits. We investigated whether selective CTL-mediated dysfunction of hippocampal interneurons may contribute to temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). METHODS:We developed a mouse model based on virus-mediated expression of ovalbumin (OVA) selectively in CA1 hippocampal interneurons into transgenic mice harboring OVA-specific CD8+ T cells. This approach enables interneuron-specific immune targeting within the hippocampus. RESULTS:Interneuron-specific OVA expression in hippocampal CA1 resulted in rapid CD8+ T cell infiltration and targeting of inhibitory neuronal populations, accompanied by acute symptomatic seizures beginning 4 to 6 days after transduction. This acute inflammation-associated phase was followed by a chronic phase characterized by persistent spontaneous recurrent seizures (SRS), HS, sustained microglial activation, and astrogliosis. In the chronic stage, reduced Reelin expression coincided with interneuron vulnerability, granule cell dispersion (GCD), and mossy fiber reorganization. Proliferation analyses suggest that GCD results from displacement of pre-existing granule cells rather than aberrant neurogenesis, and is associated with gliosis and reduced Reelin expression. INTERPRETATION:These findings demonstrate that selective CTL-mediated targeting of hippocampal CA1 interneurons induces seizures and hippocampal remodeling. This model shapes current concepts of epileptogenesis by showing that cell type-specific autoimmune mechanisms recapitulate key features of TLE, including GCD. ANN NEUROL 2026.
OBJECTIVE:Parkinson's disease (PD) lacks reliable, minimally invasive biomarkers for diagnosis. This study aimed to identify and validate PD-specific plasma extracellular vesicle (EV)-associated proteins. METHODS:Plasma EVs were isolated by ultracentrifugation and characterized. Proteomic profiling of total plasma EVs from PD patients and healthy controls was performed, and a candidate protein identified after analysis was validated by enzyme-linked immunosorbent assay. Diagnostic accuracy was evaluated using receiver operating characteristic and precision-recall curve analysis. Disease specificity was examined in progressive supranuclear palsy and amyotrophic lateral sclerosis. Histochemical and immunofluorescence analyses were conducted in human and mouse PD brain tissue. RESULTS:Proteomic analysis identified distinct PD-specific EV proteins, including cofilin 1 (CFL1), which was significantly enriched in EVs isolated from PD. EV-CFL1 levels were significantly elevated in PD compared with healthy controls (p < 0.0001). Receiver operating characteristic analysis showed strong diagnostic performance for EV-CFL1 (area under the curve 0.87). Also, EV CFL1 levels could distinguish PD from progressive supranuclear palsy patients (area under the curve 0.914). CFL1 was enriched in L1 cell adhesion molecule-positive EVs, indicating a possible neuronal origin. CFL1 was detected in both human and mouse PD brain sections. Importantly, EV-CFL1 levels were independent of age, disease stage, and motor severity. INTERPRETATION:EV-associated CFL1 represents a PD-specific, blood-based marker with strong diagnostic accuracy and can distinguish PD from atypical parkinsonism. The presence of CFL1 was confirmed in human and mouse PD brain tissue, and its accumulation in PD brain suggests a possible role in disease pathogenesis. ANN NEUROL 2026.
OBJECTIVE:Hospitalized people with Parkinson's disease (PwP) face increased risks of medication errors and discharge to non-home settings, both of which are associated with adverse outcomes. This study assessed differences in medication error rates and discharge outcomes before and after implementation of a dedicated inpatient program for hospitalized PwP. METHODS:During 2023, a Parkinson's disease (PD) inpatient program was implemented and refined combining: (1) an electronic health record (EHR) census for identification of hospitalized PwP; (2) inpatient monitoring and alignment of inpatient and outpatient regimens by movement-disorders-trained advanced practitioners; (3) customized EHR alerts and levodopa orders; (4) pharmacist support, and (5) staff education. Medication error rates and clinical outcomes were compared between January and June 2024 (post-implementation phase) and a pre-implementation retrospective cohort from 2018. RESULTS:From January to June 2024, 366 post-implementation admissions were monitored. Among those receiving contraindicated medications, the median number of doses decreased from 2 (interquartile range [IQR] = 1-6) during pre-implementation to 1 (IQR: 1-2) post-implementation (p = 0.015). Days with a levodopa dose deviation decreased from 43.1% to 38.3%, p < 0.0001, improper levodopa formulation substitutions from 18.6% to 5%, p < 0.0001, timing deviations from 72.2% to 51.8%, p < 0.00001, missed doses from 21.5% to 16.8%, p = 0.013, and discharged to non-home settings from 44.8% to 38.3%, p = 0.038. INTERPRETATION:Following implementation of a multidisciplinary and proactive inpatient program, reductions in medication errors and improved discharge outcomes were observed among PwP. ANN NEUROL 2026.
OBJECTIVE:To characterize magnetic resonance imaging (MRI)-based glymphatic surrogates in Huntington's disease (HD) using MRI measures of perivascular diffusivity and structural perivascular alterations across multiple large cohorts. METHODS:We analyzed 2,731 MRI sessions from 880 participants across 3 large retrospective HD cohorts. HD gene carriers were grouped by the HD Integrated Staging System into stage 0 to 3. We assessed the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and MRI-visible enlarged perivascular spaces (EPVS). Linear mixed-effects models examined group differences and associations with motor, cognitive, and functional measures. Likelihood ratio tests evaluated their added explanatory value beyond established imaging, genetic, and demographic variables. RESULTS:Left ALPS indices were lower at more advanced disease stages (stage 1: -3.71%, Cohen's d: -0.25; stage 2: -4.33%, Cohen's d: -0.31; Stage 3: -6.43%, Cohen's d: -0.46; all p < 0.05) compared with controls, independent of demographic and clinical variables. EPVS burden showed region-specific patterns, with subcortical EPVS volume fraction increased in HD (stage 1-3: +49.9% to +63.7%, Cohen's d: 0.47 to 0.55, p < 0.0001), whereas white matter EPVS volume fraction decreased at Stage 3 (-13.8%, Cohen's d: -0.21, p < 0.05). Lower ALPS indices correlated with higher motor impairment (p < 0.0001) and reduced functional capacity (p < 0.01). Both ALPS and EPVS improved prediction of composite HD progression beyond CAG-Age Product Score and striatal volume. INTERPRETATION:Multimodal MRI revealed stage-dependent alterations in MRI-based glymphatic surrogates with low to moderate effect sizes. These findings suggest that DTI-ALPS and EPVS metrics offer complementary, noninvasive indicators of HD pathology derivable from routine imaging protocols. ANN NEUROL 2026.
Background:Depression is a common mental health condition that is often misunderstood, leading to delays in early intervention. It can impair working memory, reduce hope, and negatively affect psychological well-being. Although Cognitive Behaviour Therapy (CBT) is an effective first-line treatment, its structured and cognitively demanding approach may reduce treatment adherence in the Indian context. Therefore, there is a need for brief and accessible early interventions. The present study examined the effectiveness of a single-session Solution-Focused Circle Technique, derived from Solution-Focused Therapy, for the preliminary management of depression. Purpose:The present study investigated the effectiveness of single session Solution-Focused Circle Technique on working memory, hope, and psychological well-being among individuals with depression. Method:The study adopted a controlled pretest-posttest design with 40 participants aged 25-45 years, diagnosed with mild to moderate depression as per ICD-10 DCR criteria, selected through purposive sampling. Participants were systematically allocated equally into experimental and control groups. The experimental group received a 30-minute single session of Solution-Focused Circle Technique, while the control group underwent a 30-minute waiting period. BDI-II, Digit Span Test, Adult Hope Scale, and Psychological Wellbeing Scale were used, and data were analyzed using descriptive statistics, independent and paired-sample t-tests. Results:The experimental group showed significant improvement in working memory, hope, and psychological well-being compared with the control group. Findings suggest that the Solution- Focused Circle Technique may help enhance working memory and reduce cognitive difficulties associated with depression. Conclusion:The findings indicated the use of solution focused circle technique to enhance cognitive function, boost hope, and improve overall well-being in individuals with depression. Thus, SFCT may serve as a brief and feasible preliminary intervention to support psychological health in this population.
Patients diagnosed with cholelithiasis, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and constipation frequently exhibit comorbid major depressive disorder (MDD). Although the underlying mechanisms remain elusive, potential genetic associations have been proposed. Leveraging extensive genome-wide association study databases, the genetic association patterns between MDD and four digestive diseases (cholelithiasis, GERD, IBS, and constipation) were systematically investigated. A hierarchical analytical approach was adopted: linkage disequilibrium score regression (LDSC), genetic covariance analysis (GNOVA), and high-definition likelihood (HDL) were employed to evaluate genome-wide correlations. Regional genetic variation was analyzed using local variation association analysis (LAVA) to pinpoint significant genomic loci. A bivariate causal mixture model (MiXeR) was further applied to quantify genetic overlap. The conditional/conjunctional false discovery rate (cond/conjFDR) approach was utilized to detect shared loci. Tissue-specific enrichment analyses were conducted using linkage disequilibrium score regression for specifically expressed genes (LDSC-SEG) to identify phenotype-relevant tissue distributions. In addition, a genetics-informed cell-type spatial mapping approach was used to generate single-cell-resolution maps of disease-associated cell populations. The findings revealed statistically significant, positive genome-wide genetic correlations between MDD and all four digestive diseases. Multiple chromosomal regions exhibiting shared genetic signals were identified through local variation analysis. Key overlapping genetic loci were uncovered via cond/conjFDR analysis. MiXeR further indicated substantial genetic overlap among these traits. Furthermore, gene enrichment assessments indicated that MDD, constipation, and IBS demonstrated significant tissue-specific enrichment in various brain regions. Genetics-informed cell-type spatial mapping analyses also revealed similar patterns of cell-type-specific distribution across related tissues. This investigation constitutes the first genomic-level evidence of genetic overlap between MDD and the four digestive diseases, elucidating shared loci that may underlie comorbidity mechanisms. These results suggest novel molecular pathways for integrated clinical prevention and therapeutic strategies.
Developing therapies for Alzheimer's disease (AD) is a pressing need. A key feature of AD is synapse loss. ApoE4, amyloid-β (Aβ)-peptides, phospho-tau, and neuroinflammation are thought to induce AD pathogenesis, but their molecular mechanisms are incompletely understood. Free Aβ-peptides whose levels decrease in AD are synaptogenic, whereas aggregating Aβ-peptides that accumulate in AD are synaptotoxic. It is unclear whether AD is driven primarily by the loss of free Aβ, the increase of aggregated Aβ, or both, nor do we know how ApoE4 affects synapses. Therefore, understanding the molecular pathways mediating synapse loss in AD is a priority in developing new therapies. ANN NEUROL 2026.
Abstract Background Using speech as objective markers for major depressive disorder (MDD) has shown promise, yet their generalizability across clinical settings remains largely unvalidated. Objective This study aimed to validate previously identified speech markers of depressive symptoms in an independent clinical cohort, thereby assessing their reproducibility and robustness for cross-site application. Methods Speech data from two independent psychiatric cohorts (RWTH Aachen and University of Oldenburg, Germany) were analyzed, comprising 135 participants (71 healthy controls, 64 MDD patients). Participants completed a positive and a negative storytelling task, over 80 temporal, lexical, and spectral speech features were extracted from the acoustic signal. Statistical analyses assessed group differences and correlations with Beck Depression Inventory (BDI-II) scores. Machine learning models trained on the Aachen data were tested on the Oldenburg cohort. Results Several temporal and spectral speech features, including utterance duration, pause duration, and MFCCs, were consistently associated with MDD diagnosis and symptom severity across both cohorts. Machine learning models trained on Aachen data achieved a classification accuracy (ROC-AUC) of 0.63 on the Oldenburg sample, demonstrating above-chance but modest transfer performance. Voice quality features (shimmer, jitter) showed more variable associations: partial correlations indicated some significant effects (e.g., shimmer and jitter during positive storytelling), whereas moderation analyses revealed interaction effects, particularly for shimmer and jitter in negative storytelling, where MDD patients exhibited higher values in the Aachen cohort but lower values in the Oldenburg cohort compared to healthy controls. Conclusions The study indicates that temporal and spectral markers of speech are relatively robust across independent clinical samples, whereas voice quality markers (shimmer, jitter) show site-dependent inconsistencies, acting as technical artifacts of varying recording conditions rather than robust biomarkers. While current speech-based classifiers remain less accurate than established self-report measures, their integration with clinical scores offers a more balanced trade-off between sensitivity and specificity. Future work should prioritize systematic evaluation across elicitation tasks, languages, and longitudinal settings to delineate which speech features are transferable and which are task-specific.
