BACKGROUND: Community reintegration is a key outcome after stroke, but many individuals experience persistent participation restrictions despite functional recovery.However, clinically interpretable indicators for identifying individuals at risk of restricted community reintegration, especially in the early chronic phase, remain unclear. OBJECTIVE: To classify levels of community reintegration and identify clinically interpretable cutoff values associated with restricted reintegration in individuals in the early chronic phase after stroke. METHODS: This cross-sectional study included 40 individuals 6-12 months post-stroke.Community reintegration was assessed using the Korean version of the Reintegration to Normal Living Index. Multidimensional clinical variables, including physical function, psychosocial and behavioral factors, social participation, and fall risk, were evaluated using validated instruments. Group comparisons, correlation analyses, receiver operating characteristic analyses, and multivariable logistic regression were performed. RESULTS: Several variables were associated with community reintegration, including physical, psychosocial, and behavioral factors. Among these, fall-related activity avoidance measured using the Survey of Activities and Fear of Falling in the Elderly showed the strongest association ( =  -0.77,  = .001) and highest discriminative ability (AUC = 0.82), with a cutoff of ≥32.5. In multivariable analysis, activity avoidance remained independently associated (odds ratio = 0.883, 95% CI = 0.795-0.980,  = .020), whereas depressive symptoms were not significant ( = .052). The model explained 51% of the variance, with 75% accuracy. CONCLUSION: Fear-related activity avoidance may be a key behavioral factor associated with community reintegration in individuals in the early chronic phase after stroke, with potential clinical utility for identifying those at risk of restricted reintegration.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. Evidence suggests a markedly elevated burden of depression among women with PCOS; however, context-specific data from South Asia, particularly Bangladesh, remain limited. This study assessed the prevalence, severity, and associated factors of depression among young Bangladeshi women diagnosed with PCOS. METHODS: A cross-sectional analytical study was conducted between December 2024 and July 2025 among 417 women aged 18-30 years with clinically diagnosed PCOS across Bangladesh. Participants were recruited from gynecology and endocrinology clinics, digital health, and online PCOS support platforms using a combined purposive and convenience-based voluntary sampling approach. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and total scores were categorized into mild, moderate, and severe depressive symptom levels. The PHQ-9 was used exclusively to assess depressive symptoms. Psychosocial variables including body image dissatisfaction, perceived family and social support, fertility concerns, and stress related to PCOS symptoms were assessed separately using structured questionnaire items developed based on relevant literature. Bivariate analyses and multivariable logistic regression were performed, with associations reported using adjusted odds ratios (aORs), 95% confidence intervals (CIs), and p-values. RESULTS: Nearly two-thirds of participants (67.4%) experienced moderate to severe depressive symptoms. Moderate depression was most common (36.0%), followed by mild (32.6%) and severe symptoms (31.4%). After adjustment, longer PCOS duration (> 2 years; aOR = 1.47, 95% CI 1.08-2.01, p < 0.05), menstrual irregularity (aOR = 2.11, 95% CI 1.34-3.32, p < 0.01), and fertility concerns (aOR = 2.87, 95% CI 1.72-4.79, p < 0.001) were independently associated with depression. Body image dissatisfaction (aOR = 0.27, 95% CI 0.15-0.48, p < 0.001) and adequate perceived social support (aOR = 0.29, 95% CI 0.16-0.51, p < 0.001) showed significant protective associations against depression. CONCLUSION: Depression is highly prevalent among young women with PCOS in Bangladesh and is strongly associated with both clinical and psychosocial factors. Integrating routine mental health screening and culturally sensitive psychosocial support into PCOS care is essential for improving overall health outcomes.

PURPOSE: Late-onset fetal growth restriction (FGR) presents clinical management challenges, often requiring frequent in-hospital fetal surveillance. Telemedicine-based computerized cardiotocography (cCTG) performed at home may offer a viable remote monitoring addition. METHODS: This single-center, open-label, a pilot randomized controlled pragmatic trial (COSMOS) was conducted in Warsaw, Poland, between 2022 and 2025. A total of 120 women with late-onset FGR, defined according to the Delphi criteria, were randomly assigned (1:1) to either a cCTG-based monitoring approach with protocol-mandated safety Doppler assessments or to standard hospital-based Doppler surveillance. The primary outcome was neonatal condition at birth (Apgar score at 5 min, umbilical artery pH). Secondary outcomes included emergency cesarean section for fetal compromise, maternal anxiety, measured using the Generalized Anxiety Disorder 7-item scale (GAD-7), number of antenatal visits, and a composite of adverse neonatal outcomes. The study protocol was registered at ClinicalTrials.gov (NCT05034861). RESULTS: There were no significant differences between groups in Apgar scores, umbilical cord arterial pH, or need for neonatal resuscitation. The rate of emergency cesarean delivery was lower in the cCTG-based group. Women in the cCTG-based group also reported significantly lower anxiety levels at delivery and required fewer antenatal visits, with no increase in adverse neonatal outcomes. CONCLUSIONS: Home-based computerized CTG within a pragmatic real-world framework appears feasible in pregnancies complicated by late-onset FGR. These findings support the potential of this approach to reduce hospital-based monitoring, maternal anxiety and in-person visits; however, these results should be considered hypothesis-generating and not indicative of clinical effectiveness. CLINICAL TRIALS REGISTRATION: Date 13.08.2021 NCT Number NCT05034861.

Loneliness has increasingly become a focal point of empirical research. In identifying psychological vulnerabilities associated with loneliness, emotion regulation difficulties have emerged as a potential risk factor. While a robust association between emotion dysregulation and loneliness is well established, longitudinal evidence remains limited. To address this gap, we surveyed a community sample ( = 492 at baseline; 374 women; = 25.47 years;  = 368 at T2,  = 229 at T3) over six months, with assessments at three time points. We tested a three-wave, time-separated mediation model examining the prospective associations between baseline emotion regulation difficulties and loneliness assessed six months later, with social anxiety and depressive symptoms at T2 specified as parallel mediators. After adjusting for prior levels of the focal constructs and concurrent associations among T2 variables, baseline emotion regulation difficulties predicted higher levels of social anxiety and depressive symptoms at T2. Only social anxiety at T2 was associated with loneliness at T3, and the indirect association from baseline emotion regulation difficulties to loneliness at T3 was supported through social anxiety. These findings suggest that emotion dysregulation may be linked to later loneliness primarily elevated social anxiety, highlighting the value of intervention approaches that target emotion regulation skills and social anxiety in efforts to reduce loneliness.

BACKGROUND Subarachnoid hemorrhage (SAH) is a neurological emergency accounting for 5% of all strokes, with mortality exceeding 50% in patients over 80 years of age. Aneurysmal SAH is particularly lethal in the elderly due to atypical presentations, including ECG abnormalities mimicking acute coronary syndromes, leading to delayed diagnosis and high complication rates. This case report highlights the diagnostic pitfalls of SAH-induced STEMI mimicry. CASE REPORT A in their 90s White woman with a remote history of diabetes presented to the Emergency Department (ED) with sudden-onset occipital headache, nausea, and hypertensive crisis (214/68 mmHg). Initial electrocardiography (ECG) showed ST-segment elevations (STEMI) in leads I/aVL with reciprocal depressions in III/aVF, prompting STEMI activation despite normal troponin levels. Emergency computed tomography angiography (CTA) revealed a ruptured 3×1 mm anterior communicating artery (ACOM) aneurysm with Fisher Grade 3 SAH. Echocardiography at admission showed normal ejection and no wall motion abnormalities. ECG performed 1 day after admission showed complete resolution of the ST-T segment changes and the patient did not require any coronary intervention. Despite successful endovascular coiling, her hospital course was complicated by Cronobacter sakazakii bacteremia, embolic infarcts, and refractory cachexia. Palliative care was initiated on hospital day 14 due to irreversible functional decline, culminating in hospice transition. CONCLUSIONS SAH-mediated autonomic dysregulation can produce STEMI-like ECG changes even in the absence of coronary ischemia. Geriatric SAH management requires balancing intervention risks against frailty and comorbidities. Early recognition of SAH-induced ECG changes from autonomic-mediated repolarization abnormalities is essential to avoid misdiagnosis and guide appropriate intervention, particularly in older patients in whom comorbidities and frailty complicate recovery trajectories.

BACKGROUND: Mainstream global mental health continues to privilege individual-level risk factors and biomedical approaches and treatments while sidelining the structural forces that shape mental distress. Despite calls for more socially embedded and decolonial approaches, policy and research too often neglect how structural phenomena such as globalization, colonialism, and neoliberal reforms directly drive mental health inequities. MAIN BODY: Drawing on Latin American traditions of social medicine-particularly Jaime Breilh's paradigm of social determination of health-this debate article critiques reductionist frameworks that fragment structural causation into depoliticized lists of risk factors. We articulate a social determination approach for mental health research and practice, emphasizing the multi-level embodiment of power relations, the historical-political organization of social life, structural drivers embedded in institutions and policies, and the role of collective agency and praxis. Illustrative vignettes from Latin America (employment, discrimination, and environment) demonstrate how historically structured processes linking global political economy, institutional arrangements, and everyday social relations become embodied as mental distress, and how participatory and mixed-method research can help document these dynamics while supporting transformative, community-led responses. CONCLUSIONS: We argue that adopting a social determination lens can reorient global mental health policy and scholarship toward structural justice, in line with recent international calls to decolonize and politicize mental health research. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Academic peer review is fundamental for scientific knowledge dissemination, and various initiatives are exploring how the peer review process could be more open, efficient and rewarding. We report an exploratory study where a live community-based review approach was integrated into the editorial workflow of an academic journal (Current Research in Neurobiology; CRNEUR). METHODS: This study was conducted with five manuscripts ('cases') submitted as preprints, which underwent Live Review-a structured collaborative review session led by PREreview, an organization with the mission to advance equity and openness in scholarly evaluation. With each case, PREreview team members facilitated a 90-min online discussion where registered participants provided real-time discussion and worked together on the online structured peer review document. Authors could join as observers or to answer questions. Participants then volunteered to write up the session notes into a final review and summary statement. Review participants had the option to sign the review. The finalized review was then published on PREreview's open preprint review platform approximately two weeks after the Live Review session, and it was assigned a CC BY 4.0 license and Digital Object Identifier (DOI) linked to the DOI of the reviewed preprint allowing reviewers to be recognized for their contribution. The published review was then incorporated into CRNEUR's editorial workflow to inform editorial decisions and manuscript outcomes. RESULTS: We quantified the speed to first and final editorial decision of the community review (n = 5) in comparison to a larger sample (n = 27) of articles that went through a standard review process at CRNEUR during the same timeframe. First decision times in days after manuscript submission of the Live Reviews were within the Inter Quartile Range (IQR) of the standard review process (community review: median = 75, IQR: 41.3; standard review: median 92, IQR: 41.5), as were final decision times (community review: median 138, IQR: 22.5; standard review: median 211, IQR: 166.0). A survey of the Live Review attendees (n = 13; 30% response rate) on a scale of 1 'Highly Disagree' to 5 'Highly Agree' showed median 'Agree' to 'Highly Agree' scores on several questions including the review being respectful, time efficient and scientifically rigorous (median scores: 5, 4, 4, respectively). CONCLUSIONS: The innovative Live Review approach was as efficient as the standard review process in the journal and was rated positively by those surveyed. The small sample size inherent to exploratory studies limits conclusions generalizing to larger sample sizes. We discuss how live, community-based review approaches could be further developed, scaled and sustained.

BACKGROUND: Eating disorders are highly prevalent among undergraduate students at colleges and universities in the United States (US). These behaviors may be associated with food insecurity and the COVID-19 pandemic, as both represent stressors that may be difficult for young adults to independently manage and cope with, turning to maladaptive coping strategies that are characteristic of disordered eating. The aim of this systematic review was to understand the relationship between eating disorders, defined by DSM-5 criteria, and food insecurity among undergraduate college students in the US, with additional consideration for the effects of the COVID-19 pandemic. METHODS: PubMed, Cochrane Library, Scopus, Global Health (Ovid), PsycInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Psychology Database were searched from 2014 to 2024 to capture eating disorders as defined by the DSM-5 criteria, searching terms representing eating disorders, food insecurity, and COVID-19. Articles were screened independently by 2 researchers using inclusion criteria agreed upon by all authors. RESULTS: Disordered eating was associated with food insecurity and changes in behavior due to the COVID-19 pandemic. All studies were cross sectional with the number of participants ranging from 98 to 1996. Due to heterogeneity in assessment tools used in studies pooling of data and direct comparison of findings was limited. While no study measured eating disorders, food insecurity, and COVID-19 together, studies did reveal that food insecurity and COVID-19 were both associated with emotional eating that may indicate a greater risk for binge eating disorder. CONCLUSIONS: While the overall data is limited, studies examining the effect of food insecurity or COVID-19 on undergraduate eating behaviors found that students experienced a significant increase in depressive and anxious symptoms contributing to disordered eating patterns. This may have a long-term impact on academic and health outcomes for young adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42024577588.

BACKGROUND: Home caregiving environments are critical to early childhood development (ECD), but evidence on the primary caregiver factors in this link is limited. This study examines associations between primary caregiver anxiety, primary caregiver role, and ECD outcomes. METHODS: This population-based survey was conducted in January 2024 across all 38 districts of Chongqing, China, using a stratified cluster sampling strategy. The Generalized Anxiety Disorder Questionnaire (GAD-7) and the Chinese Early Human Capacity Index (CHeHCI) were used to assess primary caregivers' anxiety and ECD levels, respectively. The primary caregiver role in the family was self-reported. RESULTS: In fully adjusted regression models (model 4), primary caregivers' anxiety was independently associated with child development delay, with an OR of 1.89 (95% CI: 1.75-2.05). Additionally, fathers' and grandparents' nurturing were positively associated with child development delay, with ORs of 1.24 (95% CI: 1.05-1.46) and 1.12 (95% CI: 1.01-1.25), respectively. Furthermore, the interaction between only-child status and screen time with anxiety concerning ECD is significant. Similarly, the interaction between only-child status and the primary caregiver role concerning ECD is significant. CONCLUSIONS: Primary caregiver anxiety and paternal or grandparental nurturing are significantly associated with delayed ECD, with only-child status and screen time further interacting with these factors. These findings highlight the need for family‑centered interventions targeting primary caregiver mental health.

Concerns about the mental health of young people have increased in recent years, and the knowledge of education professionals about mental health disorders is closely related to the identification of young people with these problems. Due to the scarcity of instruments to measure this knowledge, the present research aimed to develop and validate tests to measure knowledge about adolescent depression and anxiety to be answered by adults in the school system. We used a quantitative, non-experimental, and cross-sectional design. A non-probabilistic purposive sampling method was used to select participants. The sample comprised 10 expert judges for content validation, 16 teachers for cognitive interviews, and 304 professionals from educational establishments for administering the tests. Items were developed based on a literature review and the DSM-5; concordance among judges was calculated using Aiken's V coefficient. Difficulty and discrimination analyses were carried out using Classical Test Theory (CTT), a well-established framework that is well-suited to the sample size and the exploratory nature of this study. Group contrast was used as validity evidence, and the Kuder-Richardson reliability coefficient was calculated. In total, 45 items resulted; the depression test has 17 items in the symptoms dimension and 10 in risk factors, and the anxiety test has 12 in the symptoms dimension and 6 in risk factors. In terms of reliability, the depression test yielded coefficients of 0.864 for the symptoms dimension and 0.742 for the risk factors dimension. The anxiety scale showed coefficients of 0.873 and 0.846 for the symptoms and risk factors dimensions, respectively. The results provide preliminary psychometric evidence of content validity and internal consistency, based on a non-probabilistic regional sample from southern Chile. Future research should replicate these findings in larger, more diverse samples and apply advanced modeling approaches, such as Item Response Theory, to further evaluate the instruments' properties.

BACKGROUND: Depression is a leading cause of mental and physical disability globally, with its onset and progression influenced by a complex interplay of dietary, psychological, and biological factors. Recent research suggests a link between sugar-sweetened beverage (SSB) consumption and depression risk, although the potential biological pathways underlying this association remain poorly understood. METHODS: This study utilized data from 192,045 participants in the UK Biobank to examine the prospective association between SSB consumption and incident depression using Cox proportional hazards models. SSBs were defined as the sum of five beverage categories assessed via the Oxford WebQ 24-hour dietary recall. Directional consistency of the association was further examined across three external supporting datasets encompassing diverse populations: NHANES, YRBSS, and the Jiangsu Provincial Database. We further investigated whether proteins, metabolites, inflammatory markers, and brain imaging phenotypes may serve as candidate mediators statistically consistent with mediation of the SSB-depression association. RESULTS: High SSB consumption was associated with an 18% higher risk of incident depression compared with non-consumers (HR = 1.18; 95% CI: 1.11-1.25), with consistent directional associations observed across external supporting datasets. A plasma proteomic signature comprising 229 proteins was constructed using elastic net regularization and was associated with an increased risk of incident depression. Exploratory mediation analyses identified 72 proteins, 36 metabolites, and 5 inflammatory markers as candidate mediators, with IL1RN showing the strongest protein-level candidate mediating effect (9.6%), and Unsaturation and neutrophil count showing the strongest metabolite- and inflammatory marker-level effects, respectively. CONCLUSIONS: This study provides preliminary evidence that proteins, metabolites, and inflammatory markers may serve as candidate mediators statistically consistent with mediation of the association between SSB consumption and incident depression. These findings are exploratory and hypothesis-generating, and future experimental studies are needed to validate these candidate pathways and assess their potential as targets for dietary interventions in depression prevention.

BACKGROUND: The aim of this study was to develop a web-based psycho-educational intervention for parents of adolescents with anorexia nervosa and carry out a mixed method evaluation of its acceptability and feasibility. METHODS: After developing the intervention, we recruited parents from 19 families of adolescents with AN engaged in family-based therapy at an outpatient specialist center for eating disorders. Participants were given 6-month access to the intervention. Acceptability, feasibility, parental well-being and mental health, and family functioning were collected at baseline and again three months after baseline. RESULTS: Among the 11 parents from families who participated and accessed the intervention, the majority rated the intervention as satisfying (median = 6, IQR = 5-7), and easy to use (median = 7, IQR = 6.5-8.3). Frequency of use was about once a month. No significant differences between baseline and follow-up were found for parental well-being and mental health. We observed an increase in parental self-efficacy with a large effect size (p = 0.07, rs = -0.52), suggesting a potentially meaningful association. Parents identified positive aspects of the intervention as ease of access, comprehensive content and a positive impact on their approach to their child's illness. CONCLUSIONS: This study suggests that an add-on digital intervention to family-based treatment for parents of adolescents with AN is acceptable and feasible. Satisfaction, ease of navigation, and finding answers to questions were positively rated. Web-based or computerized psychoeducation for parents can be a valuable addition to treatment for adolescent AN.

BACKGROUND: Evaluating and addressing the mental and behavioral health issues of patients with spinal cord injury (SCI) during the rehabilitation process is essential. This systematic review and meta-analysis investigated the prevalence of mental disorders post-traumatic SCI and evaluated psychosocial interventions, leveraging a Knowledge Graph of Spinal Cord Injury (SCIKG) to overcome limitations of traditional literature searches. METHODS: The SCIKG integrated structured ontologies (SNOMED CT, UMLS, MeSH) to enable hierarchical semantic reasoning across mental disorder subconcepts. SPARQL queries identified literature from PubMed, Embase, PsycINFO, Web of Science, and Cochrane Central up to July 2025, supplemented by citation tracing. Two researchers independently screened studies against predefined criteria. Prevalence was pooled using DerSimonian-Laird random-effects models (RevMan 5.4; Stata metaprop) to account for heterogeneity (I > 50%). SCIKG quality was assessed across Coverage, Accuracy, Freshness, and Consistency dimensions RESULTS: From 16,861 screened records, pooled prevalence estimates of anxiety, depression, post-traumatic stress disorder (PTSD), cognitive impairments, suicide ideation, drug abuse, and sleep dysregulation post-SCI were 23% (95% confidence interval (CI), 21%-26%), 24% (95% CI, 22%-26%), 25% (95% CI, 21%-29%), 55% (95% CI, 27%-82%), 18% (95% CI, 12%-24%), 36% (95% CI, 30%-42%), and 41% (95% CI, 8%-73%), respectively. Subgroup analyses revealed significant variations: Western cohorts reported 30% higher anxiety than Asian populations; self-report tools overestimated depression by 40% versus clinical interviews; violence-related SCI increased PTSD risk by 75%. Psychosocial interventions mainly focused on specific subgroups in SCI patients with increased levels of pain, psychological distress, or pressure ulcers. Studies indicated inconsistent enhancements in participants' psychosocial adaptation, cognitive appraisal, and mental health. However, no significant effect was observed on their coping abilities. CONCLUSIONS: Mental disorders are prevalent and heterogeneously distributed post-SCI, influenced by cultural, methodological, and injury-phase factors. Knowledge graphs enhance evidence synthesis precision, revealing critical gaps in assessment standardization. Routine screening with validated, culturally adapted tools is warranted. Future research must prioritize phase-stratified designs, SCI-specific diagnostic thresholds, and large-scale trials of tailored psychosocial interventions. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Suicide prevention among older adults is a major public health concern in Japan, where the population is rapidly ageing. In 2020, approximately 40% of all suicide deaths occurred among people aged 60 years and older. Previous suicide prevention efforts have focused primarily on early detection and management of depression, while the social determinants of suicide among older adults remain underexplored. This study examined the associations between social indicators, aggregated lifestyle-related data derived from health checkups, and suicide rates among older adults to inform policy development. METHODS: Using publicly available data, we examined the associations between the standardised mortality ratio (SMR) for suicide and socioeconomic factors, lifestyle, and lifestyle-related diseases among adults aged 60 years and older across secondary medical areas, which represent practical administrative units for implementing public health policies. Nonparametric correlation and multiple regression analyses were conducted. RESULTS: Multiple regression analysis showed positive associations between suicide SMR and hypertension, smoking, daily alcohol consumption, older adult single-person households, and employment rate of older adults among men. The analysis showed negative associations with the number of psychotherapists and psychiatrists and income per taxpayer among women. CONCLUSIONS: Suicide risk among older adults demonstrates distinct gender-specific determinants. Preventive strategies should integrate health-related behaviours, socioeconomic factors, and mental health resource availability, and should be adapted to local contexts to effectively mitigate suicide risk, while acknowledging the limitations inherent in the ecological study design.

Social stress, beneficial for evaluating threats and resource opportunities, influences the development of anxious and depressive disorders. Stress responses are initiated via a pro-stress circuit in the anterior region of the basolateral amygdala (aBLA). This circuit contains pyramidal glutamatergic neurons that express genetic markers Camk2α, Rspo2, and Hcrtr1, which enhance stress-vulnerable behaviors via OrxR activity, and are inhibited directly by OrxR activation on Gad1, Hcrtr2, Cck GABAergic neurons. Our results have suggested stress circuitry in BLA is modulated by OrxR and OrxR activity, which counterbalance stress responsivity via Rspo2-positive glutamatergic neurons in aBLA, but whether these effects are consistent with systemic delivery is unknown. These receptor-dependent biases contribute to behavioral, physiological and molecular outcomes associated with psychiatric disorders, such as anxiety, depression, and post-traumatic stress disorder. Administration of a selective orexin receptor cross-over (SORCO; OrxR antagonist and OrxR agonist combination) treatment alleviates anxiogenic behavioral outputs in socially stressed mice, by decreasing escape latency in stress-vulnerable (Stay) mice (phenotypic reversal; vulnerable to resilient), and reducing the time spent freezing in response to the presence of a social aggressor (socially induced) in stress resilient (Escape) mice. Behavioral results coincided with a decrease in Rspo2 and an increase in Hcrtr2 gene expression in aBLA of SORCO-treated Stay mice, and an increase in Akt3 and Mtor transcription in Stay mice treated with an OrxR agonist (YNT-185). Our findings indicate that a combination of OrxR drugs (SORCO) provides potentially therapeutic outcomes through modifications of stress neurocircuitry, triggered by increasing expression of genes associated with neuroplasticity.

Depression is a recognized risk factor and potential prodromal feature of Alzheimer's disease (AD). While associations between depressive symptoms and AD pathology have been observed using cerebrospinal fluid (CSF) and PET imaging, it remains unclear whether these relationships can be captured by accessible plasma biomarkers, particularly the highly specific phosphorylated tau-217 (p-Tau217). We analyzed 615 participants from Alzheimer's disease Neuroimaging Initiative (ADNI) cohort, of whom 374 had minimal depressive symptoms (MDS). Plasma biomarkers included phosphorylated tau-217 (p-Tau217), amyloid-β 42/40 ratio (Aβ42/Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Linear regression models and mediation analyses were employed to examine associations between MDS, plasma biomarkers (p-Tau217, Aβ42/Aβ40, NfL, and GFAP), and cognitive impairment, with adjustments for age, sex, and APOE ε4 carrier status. Participants with MDS demonstrated significantly elevated plasma p-Tau217 levels (mean difference = 0.105, 95% CI [0.046, 0.163]; P < 0.001) and reduced Aβ42/Aβ40 (mean difference = -0.024, 95% CI [-0.041, -0.006]; P = 0.007) compared with those without MDS. These associations were primarily observed in non-demented individuals and influenced by age, sex, and APOE ε4 status. In mediation analyses, plasma p-Tau217 accounted for 41.57%-42.18% of the association between MDS and cognitive impairment, while Aβ42/Aβ40 mediated 7.13%-8.45% of this relationship. Plasma biomarkers of p-Tau217 and Aβ42/Aβ40 were associated with early depressive symptoms and mediate their associations with cognitive impairment. These findings identify plasma p-Tau217 as a key mediator linking MDS to cognitive impairment, extending evidence from CSF to accessible blood-based biomarkers. This highlights the value of monitoring plasma p-Tau217 and Aβ42/Aβ40 to unravel the pathological basis of depressive symptoms in early AD.

This study examined modulations of the cardiac autonomic nervous system, neuromuscular performance and psychological states during the menstrual cycle (MC) in naturally menstruating women. Fifteen healthy young females were tested during menstruation, estimated late follicular, and estimated mid-luteal phases. Each session included mood and motivation assessments, resting heart rate variability (HRV) analysis and a maximal voluntary isometric contraction test of the knee extensors. Our data revealed a significant decrease of the parasympathetic activity reflected by lower vagally derived HRV indices (root mean square of successive R-R interval differences and high frequency spectral component) during the mid-luteal phase compared to both menstruation and late follicular phases. However, no significant difference was detected for maximal force, rate of force development (RFD), and associated electromyographic activity (EMG). Among psychological variables, the Depression subscale score was the only one that increased during the late follicular phase. No significant correlations were observed between most HRV indices, neuromuscular performance variables, and psychological measures. However, perceived Vigour was positively associated with EMG activity during the RFD phase. In addition, autonomic balance was related to RFD, with low frequency (nu) positively and high frequency (nu) negatively correlated with explosive force production. These findings suggest cardiovagal modulation across the MC. HRV appears to be a sensitive physiological marker of menstrual-related autonomic shifts, with potential implications for monitoring female athletes.

Psychological distress is a major public health issue with multisystemic effects, yet its multidimensional nature and specific links to urogenital disorders remain inadequately characterized due to methodological limitations of prior studies. This large-scale study utilized data from the UK Biobank (N = 501,988) to investigate both cross-sectional and prospective associations between six validated psychometric instruments including emotional distress (MHS-20), neuroticism (N-12), somatic symptoms (RDS-4), depression (PHQ-9), and anxiety (GAD-7) and eight non-infectious urogenital conditions. Multivariable-adjusted logistic and Cox proportional hazards models were employed, controlling for demographic, socioeconomic, lifestyle, and clinical confounders. Multiplicative interaction analyses were introduced to evaluate effect modification by age, sex, and menopausal status. Higher scores across all psychological scales were associated with increased incidence of urogenital diseases, with the strongest associations observed for RDS-4 with urgency urinary incontinence (HR = 1.48, 95% CI: 1.39-1.58), IC/BPS (HR = 1.49, 95% CI: 1.25-1.78), and pelvic pain (HR = 1.49, 95% CI: 1.35-1.64). Interaction analyses indicated significant effect modifications by age, sex, and menopausal status for specific bladder and pelvic floor disorders. For sex-specific patterns, females exhibited stronger associations for IC/BPS and other bladder disorders, whereas pelvic floor dysfunction showed stronger associations in males. Associations for pelvic myalgia remained consistent across sexes, indicating no significant effect modification. Chronic prostatitis showed limited to no prospective associations with psychological distress. Multidimensional psychological distress represents a risk factor for urogenital disorders, with notable demographic variations. These findings support the incorporation of structured psychological assessments into urological practice to facilitate a more integrated, biopsychosocial approach to patient management.

Ebselen has been shown to induce a positive emotional processing bias and brain neurochemistry in healthy volunteers. However, little is known about its effects on resting-state functional connectivity (rs-FC) in depressed patients who show inadequate responses to standard antidepressants. The study aimed to investigate the effect of ebselen as an add-on treatment on rs-FC in this population. We conducted a randomised, double-blind, placebo-controlled trial involving depressed patients who were not responsive to their current treatment. Participants received either ebselen 600 mg twice daily or placebo for seven days. Resting-state functional magnetic resonance imaging was conducted at baseline and on day seven. Resting-state data were analysed using seed-based analysis and independent component analysis. Greater changes in rs-FC between the pregenual anterior cingulate cortex and the cerebellum were observed in ebselen than in placebo, but became negligible after corrections for multiple comparisons. We identified treatment effects within visual networks and between visual and sensorimotor networks, however, these did not survive correction for multiple comparisons. Short-term ebselen treatment in depressed patients with inadequate antidepressant responses did not produce significant changes in rs-FC. These findings may reflect limitations related to the short treatment duration and small and heterogeneous sample.

Cervical cancer substantially impairs HRQoL, particularly among women in socially and economically productive age groups. EQ-5D utility values are important inputs for quality-adjusted life-year estimation, cost-utility analysis, and health technology assessment; however, pooled EQ-5D estimates for cervical cancer remain limited. This PRISMA 2020-compliant systematic review and meta-analysis searched PubMed, Embase, Scopus, and the Cochrane Library from inception to July 2025. The protocol was registered in PROSPERO (CRD420251077051). Eligible studies included adults with cervical cancer reporting EQ-5D-3 L, EQ-5D-5 L, EQ-5D VAS, or EQ-5D domain-level outcomes. Random-effects meta-analysis was used to estimate pooled mean utility and VAS scores. Heterogeneity, publication bias, sensitivity analyses, subgroup analyses, prediction intervals, and meta-regression were assessed. Twenty-four studies including 281,958 participants from 15 countries were included. Seventeen studies contributed to the EQ-5D utility meta-analysis, yielding a pooled mean utility score of 0.79 (95% CI: 0.73-0.85; 95% prediction interval: 0.52-1.05; I² = 99.6%). Seventeen studies reported EQ-5D VAS scores, with a pooled mean of 71.82 (95% CI: 67.95-75.69; 95% prediction interval: 54.54-89.11; I² = 98.3%). Stage-specific estimates were inconsistent, particularly for Stage IV disease, and should be interpreted cautiously because of small sample size, potential survivor bias, and high between-study variability. Pain/discomfort and anxiety/depression were the most frequently affected EQ-5D domains. Cervical cancer is associated with reduced HRQoL. The pooled EQ-5D estimates provide useful reference values for economic evaluations and HTA, but substantial heterogeneity and wide prediction intervals indicate that local adaptation and cautious interpretation are required.

Understanding physical functioning during fasting is critical for both survival and everyday performance. Thus, the main aim of the present study was to determine the effects of a 6-day fasting period on fine motor skills, drop jump (DJ) performance, and neuromuscular properties of the ankle plantar flexors in healthy, physically inactive men. Non-obese men (n = 14) completed a 6-day fast followed by 7 days of habitual diet. Changes in mood state, fine motor skills, reflexes (V-wave, H-wave and M-wave), involuntary muscle torque, maximal voluntary contraction (MVC), central activation ratio (CAR) during MVC, and DJ performance were measured. Fasting had no effect on physical performance (i.e., fine motor skills and DJ) and MVC; however, it increased subjective perceived fatigue, and reduced the H/M and V/M amplitude ratios after both 4 and 6 days of fasting (P < 0.05). In contrast, a decrease in CAR and an increase in H-reflex latency were observed only after 6 days of fasting (P < 0.05). Following the return to a habitual diet, CAR and reflexes returned to prefasting values (P > 0.05), while improvements in mood, including decreased perceived fatigue and depressive symptoms, and increased vigor were accompanied by enhanced fine‑motor performance (P < 0.05). To conclude, despite adaptive modifications at both supraspinal and spinal levels and increased fatigue, MVC, jump performance, and fine‑motor skills were preserved after prolonged fasting. After resuming a habitual diet, changes at supraspinal and spinal level returned to baseline, and mood improvements coincided with enhanced fine-motor performance.Trial registration Retrospectively registered on ClinicalTrials.gov (NCT05545943).

Virtual reality (VR)-assisted avatar therapy has shown promising effects for reducing voice-related distress and overall severity of persistent auditory verbal hallucinations (AVH) in psychosis, yet the mechanisms underlying these improvements remain unclear. Emotional processes may play a role during therapeutic encounters with simulated voices, but it is unknown whether treatment effects involve broader changes in emotion regulation. We conducted secondary analyses of the CHALLENGE randomized clinical trial (N = 270), comparing a seven-session immersive VR-based avatar therapy with enhanced treatment as usual (standard care plus additional supportive counseling). Mediation models tested whether changes in cognitive reappraisal or expressive suppression, assessed using the Emotion Regulation Questionnaire (ERQ), mediated treatment effects on AVH severity and frequency at treatment end. Randomization to VR-assisted therapy did not significantly change ERQ reappraisal or suppression. Although higher reappraisal at follow-up was associated with lower AVH severity, no significant indirect effects were observed. These findings suggest that improvements following VR-assisted avatar therapy are unlikely to be explained by changes in self-reported trait emotion regulation strategies and may instead reflect more context-specific processes during voice confrontation.

Developing clinically useful brain-based biomarkers remains a central challenge in translational psychiatry and neurology. Traditional approaches focusing on disorder-specific signals have shown limited clinical utility. EEG, a scalable and non-invasive measure of brain function, illustrates the value of an alternative perspective: transdiagnostic and dimensional biomarker development. Here, we use low-frequency activity (LFA) as an illustrative example to demonstrate this framework. We synthesize evidence from 176 EEG studies across chronic pain, migraine, fatigue, and depression and identify increased low-frequency activity (LFA) as the most consistent alteration across studies. Crucially, this absence of disorder specificity does not diminish its clinical value. Instead, it points to shared neural dysfunction, consistent with frameworks of thalamo-cortical dysrhythmia and excitation-inhibition imbalance. These processes may underlie shared symptom dimensions, such as negative affect, cognitive dysfunction, and somatic manifestations. Accordingly, such transdiagnostic, dimensional markers could support prevention, monitoring, stratification, and neuromodulation across disorders, exemplifying precision neuroscience via mechanistically grounded, clinically actionable biomarkers.

Ineupatorolide B (InB), a sesquiterpene lactone with anti-inflammatory and anti-tumor properties, has not previously been evaluated for antidepressant effects. Given the central role of the gut-brain axis in stress-related mood disorders, we investigated whether InB alleviates depression-like phenotypes in mice exposed to chronic social defeat stress (CSDS) through microbiota- and vagus-dependent mechanisms. CSDS-susceptible mice received vehicle, fluoxetine, or InB and were assessed using behavioral paradigms, plasma inflammatory cytokine measurements, and analyses of synaptic-related protein expression in the medial prefrontal cortex (mPFC). CSDS induced robust depression-like behaviors, elevated interleukin-6 and tumor necrosis factor-α, caused splenomegaly, and reduced PSD-95 and BDNF expression in the mPFC. Repeated InB administration significantly reversed these behavioral, inflammatory, and synaptic abnormalities. 16S rRNA gene sequencing revealed that CSDS disrupted gut microbial α- and β-diversity, whereas InB treatment largely normalized these alterations and restored depression-associated short-chain fatty acids, including isobutyric and valeric acid, consistent with reestablishment of microbial metabolic homeostasis. Importantly, subdiaphragmatic vagotomy abolished the antidepressant-like, anti-inflammatory, and synaptic effects of InB, demonstrating that its efficacy requires intact vagus nerve-mediated gut-brain signaling. Together, these findings identify vagus-dependent modulation of the microbiota-immune-synaptic axis as a mechanistic pathway through which InB exerts antidepressant effects and highlight this compound as a potential microbiota-targeted therapeutic strategy for depression.

Childhood maltreatment (CM) has been consistently associated with increased risk and poorer outcomes in bipolar disorder (BD). However, the behavioural and cognitive mechanisms linking CM and suicidality remain poorly understood, limiting the development of targeted preventive interventions. We estimated a regularised partial correlation network to explore the interplay between CM subtypes (emotional, physical, or sexual abuse; emotional and physical neglect), cognitive domains (attention/processing speed, executive function/working memory, socio-emotional cognition, decision-making), impulsivity traits (attentional, motor, non-planning), and suicidal behaviours (ideation, planning, attempts) in 249 euthymic individuals with BD (mean age = 46.14, SD = 8.60; 59.84% female; 71.89% BD type I). CM was assessed using the Childhood Trauma Questionnaire (CTQ), cognition with a comprehensive neuropsychological battery, impulsivity with the Barratt Impulsiveness Scale (BIS-11), and suicidality with the Columbia Suicide Severity Rating Scale (C-SSRS) and structured interview. Age, sex, and social desirability (CTQ minimisation/denial subscale) were included as covariates. CM was associated with both cognitive functioning (poorer executive function and working memory, attention/processing speed, and socio-emotional cognition) and suicidality (suicidal ideation and, to a lesser extent, suicide attempts). Emotional abuse was linked to suicidal ideation (strongest association among CM subtypes; r = 0.27, p <0.001) and showed the highest centrality within the network (strength z = 1.76; expected influence z = 1.95). All CM subtypes were associated with impulsivity traits. Motor impulsivity emerged as a behavioural bridge between CM and suicidality (bridge expected influence z = 0.21), whereas higher socio-emotional cognition, particularly the ability to manage emotions, was associated with fewer suicide attempts. These findings highlight specific cognitive and behavioural mechanisms linking CM and suicidality in BD. Emotional abuse and socio-emotional cognition represent promising targets for trauma-informed and personalised interventions.