Social Psychiatry and Psychiatric Epidemiology

ObjectiveThere is little longitudinal research investigating links between violence exposure and mental disorders among children in low- and middle-income countries (LMICs), despite high rates of violence. We examined cross-sectional and longitudinal violence-mental health associations among children in a large South African birth cohort, the Drakenstein Child Health Study, including direct clinical interviews capturing childrens mental disorders. MethodIn this birth cohort (N=974), we assessed lifetime violence exposure and four subtypes (witnessed community, community victimization, witnessed domestic, domestic victimization) at ages 4.5 and 8-years via caregiver reports. At 8-years, caregivers completed the Child Behaviour Checklist; and psychiatric disorders were assessed using the Mini-International Neuropsychiatric Interview for Children and Adolescents, a self-report measure. We tested for associations using linear/logistic regressions, adjusted for confounders. ResultsMost children (91%) had experienced violence by 8-years. Cross-sectionally, total violence exposure was associated with total (B =0.49 [95% CI 0.32, 0.66]), internalizing (0.32 [0.17, 0.47]), and externalizing problems (0.46 [0.31, 0.61]), and with increased odds of disorder at 8 years (aOR=1.09 [1.05, 1.13]). Longitudinally, total violence exposure up to 4.5-years was associated with total (B=0.27 [0.03, 0.52]), internalizing (0.24 [0.04. 0.44]), and externalizing scores (0.23 [0.008, 0.45]) at 8-years, but not with increased risk of psychiatric disorders. The strongest and most consistent associations were observed for domestic versus community violence subtypes. ConclusionOur strong cross-sectional but weaker longitudinal findings suggest that recent violence exposures may be more critical than early exposures for childrens mental health. Longitudinal exploration of other violence-affected LMIC populations is urgently needed.

Objective: Childhood poverty is a high-risk context that involves diverse adversities, making it difficult to understand how poverty confers later psychopathology risk and why some children remain resilient despite growing up in poverty. To address this heterogeneity, we quantified adversity-linked vulnerability as adversity-psychopathology coupling and tested whether childhood poverty amplifies this coupling and whether multilevel inhibitory-control profiles stratify vulnerability and resilience within poverty-exposed youth. Methods: We analyzed 10,112 youth (48.4% female; mean age = 9.92 years) from the Adolescent Brain Cognitive Development Study, linking baseline cumulative early-life adversity (ELA) to later behavioral problems across 4 waves. In the stop-signal task fMRI subsample of 7,401 youth, semi-supervised clustering of inhibitory-control activation identified neurofunctional subtypes within poverty-exposed youth. We also tested temperamental inhibitory control as an additional moderator. Results: Childhood poverty amplified the association between cumulative ELA and behavioral problems at baseline ({Delta}{beta} = 0.088; P < .001) and across follow-up waves. Two neurofunctional subtypes were identified within poverty-exposed youth: subtype-1 showed greater vulnerability than higher-income peers ({Delta}{beta} = 0.149; P < .001), whereas subtype-2 showed attenuated vulnerability and did not differ from higher-income peers ({Delta}{beta} = 0.049; P = .135); this pattern persisted longitudinally. Among poverty-exposed youth in subtype-2 with high temperamental inhibitory control, the association between cumulative ELA and later behavioral problems was no longer significant. Conclusions: Childhood poverty strengthened the translation of adversity burden into later behavioral problems, but inhibitory-control profiles differentiated higher- and lower-risk pathways within poverty, highlighting inhibitory control as a candidate target for prevention.

Background Surgery is a widely used treatment option but the impact of surgery on long-term disease across socioeconomic groups is unknown. Methods Longitudinal population study using linked primary and secondary care data describing adults ([&ge;]18 years) in England recorded in the Clinical Practice Research Datalink (CPRD) between 1st January 2012 and 31st December 2021. Socioeconomic deprivation was defined using the Index of Multiple Deprivation (IMD). The exposure was surgery and primary outcome was long-term disease. Data are presented as n (%), median (IQR), and adjusted hazards ratios (HR) with 95% confidence intervals. Findings Of 18,329,659 people, 8,951,145 (48.8%) underwent surgery. 78.6% of index surgeries were elective (n=7,032,475), 21.4% were emergency (n=1,918,670). Amongst surgical patients, 4,741,188 (52.0%) were women, 3,540,136 (39.6%) from the most deprived deciles (IMD 1-4) and 994,595 (11.1%) from a minority ethnic group. Age-standardised rates of surgery were higher in deprived individuals (comparative rate ratio IMD 1 vs. IMD 10 elective: 1.11 (95% CI 1.11-1.11), emergency: 1.54 (1.54-1.54)). Age at first surgery was 42 (27-60) years for elective and 42 (25-65) years for emergency surgery overall, but lower for people from IMD 1-4 (elective: 39 (26-57) years, emergency: 38 (24-60) years). Rates of long-term disease increased following both elective (baseline 19.6%, three years 24.5%) and emergency surgery (baseline 10.3%, three years 12.3%). Risk of new long-term disease following surgery increased with increasing levels of deprivation (IMD 1 vs. IMD 10 elective: HR 1.46 (1.45-1.48), emergency: HR 1.46 (1.44-1.48)). Interpretation Surgical treatment is strongly associated with the onset of long-term disease and factors which limit healthy life expectancy. Surgery occurs at a younger age among socioeconomically deprived groups and may be linked to health inequalities. Similar but more complex patterns of inequality were seen in minority ethnic groups. Funding Barts Charity and UK Academy of Medical Sciences.

BackgroundScalable, low-burden behavioral interventions are needed to address rising subclinical mental health symptoms. However, few randomized controlled trials have evaluated ultra-brief, remotely delivered, meditation using multimodal outcome assessment under real-world conditions. MethodsWe conducted a fully remote randomized controlled trial (ClinicalTrials.gov: NCT06014281) evaluating a focused-attention meditation intervention delivered via brief instructor training and independent daily practice. A total of 299 meditation-naive adults were randomized to immediate intervention or waitlist control in a delayed-intervention design. Participants practiced [&ge;]10 minutes daily for 8 weeks within a 16-week study. Outcomes included validated self-report measures, web-based cognitive tasks, and wearable-derived physiological metrics. ResultsAcross randomized and within-participant replication phases, the intervention was associated with significant reductions in anxiety and mind wandering, with effects remaining stable during 8-week follow-up. Improvements were greatest among participants with higher baseline symptom burden. Sleep disturbance improved selectively among individuals with poorer baseline sleep. Secondary outcomes, including rumination, perceived stress, social connectedness, and quality of life, also improved. Cognitive performance showed modest improvements primarily among lower-performing participants. Resting heart rate exhibited nominal reductions. ConclusionsAn ultra-brief, fully remote meditation intervention requiring 10 minutes per day was associated with sustained improvements in psychological functioning and smaller, baseline-dependent effects on cognition in a non-clinical population. These findings support digital delivery of low-dose meditation as a scalable preventive mental health strategy.

Objective To examine the impact of acute illness on long-term health and describe any differences in these associations between socioeconomic and ethnic groups. Design Longitudinal population study. Setting Linked primary and secondary care data recorded in the Clinical Practice Research Datalink (CPRD). Participants Adults ([&ge;]18 years) residing in England registered with a primary care general practice (GP) between 1st January 2012 and 31st December 2022 who have not opted out of inclusion into CPRD and linked data sources. Socioeconomic deprivation was defined using the Index of Multiple Deprivation (IMD) and ethnicity by UK census 2011 definitions. Main outcome measures The primary outcome was new long-term disease and multimorbidity (two or more long-term diseases). We describe incidence of hospitalisation for acute illness as the exposure. Results We included 18,329,659 people, with 9,339,394 (51.0%) women, 7,430,555 (40.5%) people from the most deprived deciles (IMD 1-4) and 3,009,717 (16.4%) from a minority ethnic group. 6,038,272 (32.9%) people experienced hospitalisation for acute illness. Hospitalisation was associated with increased onset of long-term disease in those alive at the end of follow up (41.1% hospitalised vs 18.7% not hospitalised; adjusted HR 2.48 (2.47 to 2.48)). Compared to non-hospitalised, those who had been hospitalised were more likely to change from being disease free at baseline to having a new long-term disease (12.9% vs. 7.5%), develop multimorbidity (4.7% vs. 1.1%), or transition to multimorbidity if they had pre-existing disease (8.1% vs. 1.8%). Age-standardised hospitalisation rates were highest in the most deprived decile and in people with Black ethnicity. Comparative hospitalisation ratio for IMD 1 compared to IMD 10 ranging from 1.78 in 2018 to 1.96 in 2021 and for Black ethnicity compared to White ranging from 1.03 in 2017 to 1.08 in 2021. Conclusions Acute hospitalisation is a key stage in the development of long-term disease and may be an underutilised opportunity for intervention to change healthy life trajectory and reduce health inequality.

Background: Early adolescence is a common period of onset for depressive symptoms. In part, this may reflect a developmental manifestation of individual's genetic propensities as they undergo physiological and hormonal changes and interact with new environments. Many commonly proposed mechanisms assume direct effects of an individual's own genes on emerging variation in their depressive symptomatology. However, estimates of genetic influence based on analyses in unrelated individuals capture not only direct genetic effects but also genetic effects from parents and other biologically related family members. Aim: In data from the Norwegian Mother, Father and Child Cohort (MoBa), we used linear mixed models to distinguish developmentally-stable and adolescence-specific direct and parental indirect genetic effects. We examined effects of polygenic scores for major depressive disorder (MDD), ADHD, anxiety disorders, and educational attainment (EA) on depressive symptoms, which were assessed by maternal reports at ages 8 and 14. Results: Children's own MDD polygenic scores showed adolescence-specific effects on depressive symptoms ( b_PGS*wave=0.041, [95% CI: 0.017, 0.065]). Developmentally-stable direct effects from children's polygenic scores for MDD (b=0.016, [0.006, 0.039]), ADHD (b=0.024, [0.008, 0.041]) and EA (b=-0.02, [ -0.038, -0.002]) were also evident. The only evidence of indirect genetic effects was a stable effect of maternal EA polygenic scores (b=0.04, [0.024, 0.054]). Conclusion: Direct genetic effects linked to genetic liability to MDD accounted for emerging variation in depressive symptoms in adolescence. These results imply that specific etiological mechanisms related to MDD may become particularly relevant for depressive symptoms during early adolescence compared to at earlier ages.

IntroductionIn many Low- and Middle-Income countries (LMIC), access to psychological therapies for psychosis remains extremely limited, contributing to significant treatment gaps and persistent inequalities in care. Novel interventions that are effective, scalable, and culturally acceptable across diverse settings are urgently needed. AVATAR therapy is an innovative digital intervention for distressing voices in psychosis, developed in the UK. The therapy enables voice-hearers to engage in a series of facilitated dialogues with a customized computer-based representation of their main distressing voice. AVATAR3 represents the first initiative to contextually adapt AVATAR therapy and evaluate its acceptability in two LMIC settings (Ethiopia and India). Methods and analysisWe will establish Innovation and Implementation Hubs in Addis Ababa, Ethiopia (Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa) at Addis Ababa University (AAU) and Mental Health Service Users Association (MHSUA), Ethiopia) and New Delhi, India (All India Institute of Medical Sciences). Phase 1 employs formative work and diverse stakeholder engagement to inform context-specific adaptations. Reflexive thematic analysis will be used, with data synthesis informed by the Cultural Adaptation of Scalable Psychological Interventions (CASPI) framework and Ecological Validity Model (EVM). Phase 2 tests adapted AVATAR therapy through a parallel case series (n=15 per site, targeting 70% completion rate) measuring feasibility, acceptability, and safety indicators at baseline, 12-weeks, and 24-weeks. Qualitative research will explore the experiences of participants (n=10) and therapists (n=8) at each site. Ethics and disseminationEthical approval has been obtained from Addis Ababa University College of Health Science Institutional Review Board, All India Institute of Medical Sciences (AIIMS) Institutional Review Board and the Kings College London (study sponsor) Research Ethics Committee. Findings will be disseminated to inform the implementation of AVATAR therapy across diverse international settings. Strengths and limitations of this studyO_LIInterdisciplinary and participatory approach C_LIO_LIContextual adaptation of a digital innovation C_LIO_LIExpert by experience leadership and involvement from the conception of the study C_LIO_LIThe study will develop tools and share learning to support future digital mental health innovation across diverse international settings C_LIO_LIThe case-series at each site will not have a control group C_LI

Abstract Importance Stigma and discrimination against transgender and gender-diverse people are prevalent across many settings and may contribute to substantial health disparities. Objective To synthesize global evidence on the prevalence of stigma, discrimination, and resilience among transgender (trans) and gender-diverse adults. Data Sources A systematic search was conducted in PubMed, Embase, CINAHL, Cochrane Central, LILACS, and PsycInfo for articles published between January 1, 2010 and January 2, 2023. This database search was supplemented by grey literature and secondary reference searches. Article Selection Studies were eligible if they presented primary quantitative data on prevalence of stigma, discrimination, and/or resilience among trans and gender-diverse adults (aged 18 and over), with no restrictions on study design, language, or geographic region. Data Extraction and Synthesis Two independent reviewers extracted data using standardized forms, with discrepancies resolved by consensus. The JBI Critical Appraisal Checklist for Prevalence Articles was used to assess risk of bias. Random effects meta-analysis was conducted for dichotomous prevalence measures using inverse variance weighting and logit transformation; non-dichotomous prevalence data were summarized descriptively. Main Outcomes and Measures Outcomes included prevalence estimates for various forms of stigma (anticipated, perceived, internalized, and experienced), discrimination in legal/institutional settings (housing, healthcare, employment, police/prison), and resilience. Results A total of 97 articles, with data from 72,158 unique trans and gender-diverse participants across 26 countries, met inclusion criteria. Studies showed moderate levels of anticipated stigma, perceived stigma, and internalized stigma. Meta-analyses of 36 studies provided pooled estimates of discrimination prevalence across multiple domains: 21.4% in housing (e.g., eviction, rental denial), 24.6% in healthcare (e.g., denial of care, mistreatment), 32.8% in employment (e.g., hiring bias, workplace harassment), and 39.1% in police/prison settings (e.g., profiling, mistreatment). High heterogeneity was observed across studies, reflecting regional and methodological differences. Resilience scores ranged from moderate to high, indicating variation within trans and gender-diverse communities. Conclusions and Relevance This systematic review and meta-analysis found that stigma and discrimination against trans and gender-diverse adults are pervasive globally. Variation in stigma and discrimination across settings and regions underscores the need for targeted interventions and policy reforms. Funding World Health Organization through a grant from the Elton John AIDS Foundation and the Bill and Melinda Gates Foundation.

Importance: Adverse neighborhood conditions can lead to poorer health outcomes, potentially through accelerated biological aging. However, whether these relationships are explained by individual- or neighborhood-level factors remains unclear. Objective: To examine the association between neighborhood deprivation, measured by the Area Deprivation Index (ADI), and epigenetic age acceleration and assess whether individual- and neighborhood-level characteristics mediate or modify these associations. Design: Cross-sectional study using data from a Yale Stress Center study between 2008 and 2012. Data analysis was conducted from July 2025 to January 2026. Setting: Community-based sample from the greater New Haven, CT area. Participants: A total of 370 healthy adults aged 18 to 50 years without major psychiatric, medical, or cognitive disorders who provided blood samples for DNA methylation analysis. Main Outcomes and Measures: Epigenetic age acceleration measured from DNA methylation using four second-generation epigenetic clocks, with associations assessed among aging, neighborhood deprivation, and individual- and neighborhood-level factors. Results: Data were analyzed from 370 participants (212 women [57.3%], 158 men [42.7%]; mean [SEM] age, 29.3 [0.46] years). Greater neighborhood deprivation was associated with greater lifetime adversity ({beta}=0.112, p<.001) and lower educational attainment ({beta}=-0.019, p=.012), and accelerated epigenetic aging as measured by GrimAge ({beta}=0.037, p<.001), PCGrimAge ({beta}=0.019, p<.001), and PCPhenoAge ({beta}=0.041, p<.001), but not PhenoAge (p=.23). In multivariable models accounting for individual factors, neighborhood deprivation remained associated with these three clocks. Lifetime adversity partially mediated the association between ADI and accelerated GrimAge (20.3% of total effect) and PCGrimAge (23.3%). Race moderated the direct association between ADI and epigenetic aging, with stronger associations between neighborhood deprivation and accelerated GrimAge ({beta}=0.061, p=.004) and PCPhenoAge ({beta}=0.057, p=.02) observed among Black participants compared to White. Conclusions: Greater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks, with lifetime adversity partially mediating these associations. Stronger effects were observed among Black participants. These findings suggest that neighborhood environments and cumulative stress may contribute to biological aging and racial disparities in aging trajectories.

BackgroundThe severity of positive psychotic symptoms largely defines emerging psychosis syndromes. However, depressive and negative symptoms are strongly psychologically and biologically interlinked. A transdiagnostic exploration of symptom severity across early illness syndromes could enhance the understanding of shared common factors and future trajectories of mental illness. We aimed to identify subgroups based on the severity of positive, negative, and depressive symptoms and assess relationships with: 1) premorbid functioning, 2) longitudinal illness course, 3) genetic risk, and 4) brain volume differences. MethodsWe analysed 749 participants from a multisite, naturalistic, longitudinal (18 months) cohort study of: clinical high risk for psychosis (n=147), recent onset psychosis (n=161), and healthy controls (n=286), and recent onset depression (n=155). Participants were stratified into subgroups based on severity of baseline positive, negative, and depression symptoms. Baseline and longitudinal differences between groups for clinical, functioning, and polygenic risk scores (schizophrenia, depression, cross-disorder) were assessed with ANOVAs and linear mixed models. Voxel-based morphometry was used to examine whole-brain grey matter volume differences. Discovery findings were replicated in a held-out sample (n=610). ResultsParticipants were stratified into no (n=241), mild (n=50), moderate (n=182), and severe symptom (n=254) subgroups. The mean (SD) age was 25.3 (6.0) and 344 (47.3%) were male. Symptom severity was associated with poorer premorbid functioning and illness trajectory, greater genetic risk, and lower brain volume. Findings were not confounded by the original study groups or symptoms and were largely replicated. Conclusions and relevanceTransdiagnostic symptom severity is linked to shared aetiologies, prognoses, and biological markers across diagnoses and illness stages. Such commonalities could guide therapeutic selection and future research aiming to detect unique contributions to specific psychopathologies.

BackgroundHwa-byung (HB) is a Korean culture-bound syndrome characterised by prolonged suppression of anger and somatic complaints. No evidence-based digital therapeutic (DTx) has been developed for HB. We evaluated the feasibility, user experience (UX), and preliminary clinical effect of an acceptance and commitment therapy (ACT)-based DTx application, Hwa-free, for HB. MethodsAdults aged 19-80 years diagnosed with HB were enrolled in a four-week app-based intervention with assessment at baseline (Week 0), Week 2, Week 4, and Week 8 follow-up. The primary outcome was UX assessed via a 22-item survey at Week 4. Secondary outcomes included HB-related symptom and personality scales, depression, anxiety, anger expression, psychological flexibility, health-related quality of life, and heart rate variability. ResultsOf 45 screened, 30 were enrolled and 28 constituted the modified intention-to-treat population. Mean app use was 19.9 {+/-} 7.9 days (71.2% adherence over 28 days). Adverse events were infrequent and unrelated to the intervention. Positive response rates exceeded 80% for video content (items 2-4: 82.8-89.7%), HB self-assessment (86.2%), meditation therapy (86.2%), and in-app guidance (85.7%). Pre-post improvements from baseline to Week 4 were observed in 11 of 18 clinical scales, including HB Symptom Scale ({Delta} = -9.8, Cohens d = -0.92), Beck Depression Inventory-II ({Delta} = -13.3, d = -1.11), and state anger ({Delta} = -7.8, d = -0.96). The HB screening-positive rate declined from 100% at baseline to 55.6% at Week 8. ConclusionsHwa-free demonstrated adequate feasibility, acceptable UX, and preliminary evidence of clinically meaningful improvement in HB-related symptoms. Future randomised controlled trial is warranted. Trial registrationCRIS, KCT0011105

IntroductionFamily Constellation Therapy (FCT) has been widely disseminated in clinical, public health, and judicial settings despite persistent concerns regarding its theoretical basis, safety, and the limited availability of rigorous randomised evidence supporting its clinical use. ObjectiveThe aim of this systematic review is to assess the effects of FCT across all clinical conditions, explicitly considering both benefits and harms; and summarise the characteristics of studies and intervention settings used in randomised controlled trials of FCT. MethodsFollowing a prospectively registered protocol (CRD420251136190), we conducted a systematic search of seven databases (PubMed, EMBASE, APA PsycInfo, CENTRAL, BVS, Web of Science, and CINAHL) and grey literature (ICTRP and ProQuest database) without language or date restrictions to identify published and unpublished randomised controlled trials of FCT. Study selection, data extraction, risk of bias (RoB 2), and certainty of evidence (GRADE) were performed in duplicate. Statistical analyses followed a prospectively registered analysis plan with prespecified criteria for data pooling and for handling analytical limitations. ResultsNo reliable evidence was found to support the use of FCT for any condition across both clinical and non-clinical samples. All trials included were judged to be at high risk of bias and all comparisons were rated as very low-certainty evidence. Concerns regarding potential adverse effects were identified, and the available data was insufficient to establish the effectiveness of the intervention, precluding any clinical recommendation. ConclusionClinicians, policymakers, and consumers should reconsider adopting FCT while reliable evidence is not available.

AimAutistic children have a high but varied prevalence of internalizing and externalizing problems. This study aimed to identify the subtypes of internalizing and externalizing problems among autistic preschool children in Japan, examine their temporal stability, and investigate differences in participation in daily life and family outcomes across these subtypes. MethodsA prospective cohort study was conducted with 275 caregivers of autistic children aged 51-75 months. Internalizing and externalizing problems were assessed using the Strengths and Difficulties Questionnaire. ResultsLatent transition analysis identified five subtypes: Low-symptom, High-emotional, Externalizing, Comorbid, and Peer-difficulty groups. Membership in the High-emotional and Externalizing groups was relatively stable over time, whereas the Peer-difficulty group showed frequent transitions to subtypes with higher levels of internalizing or externalizing problems. Significant differences in participation in daily life and family outcomes were observed across subtypes, but these patterns were inconsistent with a simple gradient of symptom levels. ConclusionsThe novel findings that the temporal stability of subtype membership varied and that differences in participation in daily life and family outcomes were observed across the subtypes suggest that the heterogeneity of internalizing and externalizing problems may be associated with variations in childrens participation in daily life and family outcomes over time. Plain Language SummaryAutistic preschool children often experience emotional and behavioral difficulties, but the way these difficulties manifest varies widely across individuals. This study aimed to identify the patterns of these difficulties, examine how they change over time, and investigate how participation in daily life and family outcomes differ across autistic preschool children. We conducted a study with 275 caregivers of autistic children aged 4-6 years in Japan. From caregiver reports of childrens emotional and behavioral difficulties, five distinct patterns were identified: a group with mainly emotional difficulties, a group with mainly behavioral difficulties, a group with both types of difficulties, a group with relatively low levels of difficulties, and a group characterized primarily by peer-related difficulties. Our findings suggest that different patterns of emotional and behavioral difficulties are associated with differences in childrens participation in daily life and family outcomes. These differences could not be explained simply by the overall severity of difficulties but rather reflect distinct patterns based on the type of difficulty. The results indicate that autistic children face diverse difficulties that change over time.

Objectives: The primary aim of this study was to assess the feasibility of delivering an adapted problem-solving skills (PSS) intervention by quantifying the recruitment, follow-up and completion rates using a brief problem-solving intervention for people with a mental health diagnosis in two Polish prisons. Design: IAPPS is an open, multi-centred, parallel group feasibility randomised controlled trial (RCT). Setting: Two prisons in Poland. Participants: Men in custody aged 18 years and older, having a mental illness and living within the prison therapeutic unit. Interventions: The intervention consisted of an adapted PSS skills intervention plus care as usual (CAU) or care as usual only. Delivered in groups of up to five people in 1.5-hour sessions over the course of two weeks. Main outcome measures: Primary outcomes - rate of recruitment, follow-up, and feasibility to deliver the intervention. Secondary outcomes included measures of depression, general mental health, and coping strategies. Results: 129 male prisoners were screened, 64 were randomly allocated, with a mean age of 53.5 years (SD 14, range 23-84). 59 (95%) prisoners were of Polish origin. Our recruitment rate was 48%. There was differential follow up with those in the intervention group less likely to complete the post-test battery versus those who received care as usual. Outcome measures were successfully collected at both time points. Conclusions We were able to recruit, retain and deliver the intervention within the prison setting; some logistical challenges limited our assessment of intervention engagement. Our data helps to demonstrate how use of the RCT study design can be implemented and delivered within the complex prison environment. Trial registration number ISRCTN 70138247, protocol registration date May 2021

Socioeconomic inequalities in health and well-being are a major public health concern, particularly in ageing populations. Education is a key determinant shaping multiple aspects of health outcomes. We used cross-sectional data from wave 9 of the German sample (n=4,148) of the Survey of Health, Ageing and Retirement in Europe (SHARE) to test whether formal education is associated with well-being in later adulthood, with health literacy, self-rated health, and preventive health behaviours as possible mediators. Our results showed that education was positively associated with greater well-being, but only via indirect pathways. Specifically, self-rated health, health literacy, and fruit and vegetable consumption mediated the relationship between education and well-being accounting for 54.7, 24.7, and 12.6 percent of the total effect, respectively. In addition, there were significant positive correlations between education and health literacy, as well as high-intensity physical activity, daily fruit and vegetable consumption, more preventive health check-ups, and less smoking. In contrast, alcohol consumption was more common among those with higher levels of education. All health behaviours and health literacy were correlated directly or indirectly (i.e., mediated by health) with well-being. These findings highlight the importance of examining indirect pathways linking education to well-being in later life. Interventions aimed at improving health literacy and promoting healthy behaviours may help reduce educational inequalities in quality of life among older adults.

Background: Nigeria bears one of the highest maternal mortality burdens globally, with skilled birth attendance (SBA) remaining critically low in many regions. Understanding the independent determinants of SBA is essential for designing targeted interventions. Methods: This cross sectional study analyzed 21,465 births from the 2018 Nigeria Demographic and Health Survey (NDHS), a nationally representative household survey using stratified two stage cluster sampling. SBA was defined as delivery attended by a doctor, nurse, midwife, or auxiliary midwife. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the associations between SBA and maternal education, household wealth, place of residence, geopolitical region, maternal age, parity, and antenatal care (ANC) utilization, after accounting for confounding. Results: The overall prevalence of SBA was 44.9%. In the fully adjusted model, higher education (aOR = 7.01, 95% CI: 5.68-8.67), richest wealth quintile (aOR = 6.27, 95% CI: 5.27-7.46), and attending [&ge;]4 ANC visits (aOR = 3.80, 95% CI: 3.51-4.11) were the strongest independent predictors of SBA. Regional inequalities were pronounced, with SBA prevalence ranging from 17.7% in the North West to 85.6% in the South West. Crude effect estimates for education and wealth were substantially attenuated after adjustment, indicating large confounding by correlated socioeconomic factors. Conclusions: Maternal education, household wealth, ANC utilization, and geopolitical region are independent determinants of SBA in Nigeria. Scaling up ANC programs represents the most immediately actionable intervention, while long term gains require investment in girls' education and wealth equity. Targeted strategies for the northern regions are urgently needed. Keywords: skilled birth attendance, maternal mortality, Nigeria, DHS, antenatal care, logistic regression, health equity

Patient-generated streaming data from wearable and digital technologies is increasingly promoted as a means of supporting mental health monitoring and clinical decision-making. While patient acceptance of these technologies has been reported, clinician perspectives remain underexplored despite their central role in determining whether streaming data are meaningfully integrated into routine care. This study explored clinicians experiences, as well as perceived facilitators and barriers, related to integrating patient-generated streaming data into routine mental health practice. A qualitative, exploratory interview study was conducted to examine clinicians experiences and perspectives on integrating patient-generated streaming data into mental health care. Semi-structured interviews were conducted with 33 clinicians, including family physicians (n=11), psychiatrists (n=12), and psychologists (n=10). Data were analyzed using reflexive thematic analysis guided by Braun and Clarkes six-step approach. Six themes were identified. Clinicians described variable use of digital and streaming technologies, ranging from routine engagement to deliberate non-use. Streaming data were viewed as clinically valuable when they provided longitudinal and objective insights, identified physiological and behavioural pattern changes, and supported patient engagement. However, clinicians emphasized that clinical usefulness was contingent on interpretability, contextual information, and relevance to decision-making. Major barriers included poor integration with electronic medical records, time constraints, data volume, limited organizational support, and uncertainty regarding data reliability and validity. Clinicians also expressed persistent concerns about privacy, governance, and regulatory oversight, highlighting the need for clear safeguards and accountability structures. Clinicians view patient-generated streaming data as a promising adjunct to mental health care, particularly for capturing longitudinal change between visits. However, meaningful clinical integration remains constrained by usability, workflow, organizational, and regulatory challenges, as well as limited confidence in data interpretation. Addressing these barriers through improved system integration, interpretive support, validation, and governance will be essential for translating the potential of streaming data into routine clinical practice.

Background. Vietnam's disease burden has shifted from communicable, maternal, neonatal, and nutritional (CMNN) causes to non-communicable diseases (NCDs), but the tempo, drivers, and regional positioning of this transition have not been jointly quantified. We characterised Vietnam's epidemiological transition 1990-2023 against ten Southeast-Asian (SEA) peers. Methods. Using Global Burden of Disease 2023 data, we computed joinpoint-regression AAPC with 95% CI (BIC-penalised, up to three break-points) for age-standardised DALY rates and cause-composition shares. We applied Das Gupta three-factor decomposition to 1990-2023 absolute DALY change (population-size, age-structure, age-specific-rate effects) and benchmarked Vietnam's NCD share against an SDI-conditional peer trajectory via leave-one-out quadratic regression. Premature mortality was quantified as WHO 30q70 under both broad NCD and strict SDG 3.4.1 definitions, using Chiang II life-table adjustment identically across all eleven countries. Findings. The CMNN age-standardised DALY rate fell from 13,295.9 to 4,022.1 per 100,000 (AAPC -4.63%/year; 95% CI -4.80 to -4.46); the NCD rate fell only from 21,688.2 to 19,282.8 (AAPC -0.37; -0.45 to -0.30). NCD share of total DALYs rose from 52.99% to 70.67% (+17.67 pp; AAPC +1.09). Vietnam ranked fourth of eleven SEA countries in 2023 (up from sixth in 1990) and sat 5.3% above the SDI-expected trajectory. Das Gupta decomposition attributed the +10.63 million NCD DALY increase to population growth (+6.26 M) and ageing (+6.08 M); rate change removed only 1.71 M. Premature NCD mortality fell from 25.02% to 21.80% (broad, 12.9% reduction) and from 22.17% to 19.50% (SDG 3.4.1, 12.0%; Vietnam sixth of eleven) - far short of the SDG 3.4 one-third-reduction target. Interpretation. Vietnam has entered a disability- and ageing-dominated NCD phase. Meeting SDG 3.4 by 2030 requires population-scale primary prevention sized to demographic momentum.

ImportanceBlood-based biomarkers hold promise for psychiatric diagnosis and prognosis, yet clinical translation is constrained by poor reproducibility. Psychiatric biomarker studies are typically small, and demographic, behavioral, and temporal covariates often go undetected or cannot be adequately modeled. This may lead to residual confounding and unstable associations. ObservationsLeveraging UK Biobank data (N=~500,000), we systematically quantified how technical, demographic, behavioral, and temporal covariates influence 29 blood biomarkers commonly measured in research studies in psychiatry. Variance analyses showed substantial differences across biomarkers. Technical factors explained 1-6% and demographic factors explained 5-15% of the variance, with pronounced age-by-sex interactions for lipids and sex hormones. Behavioral covariates, particularly body mass index (BMI) and smoking, strongly influenced inflammatory markers. Temporal factors introduced systematic confounding. Chronotype was associated with blood collection time, multiple biomarkers exhibited marked diurnal rhythms (including testosterone, triglycerides, and immune markers), and inflammatory markers showed seasonal peaks in winter. In association analysis of biomarkers with major depression, bipolar disorder and schizophrenia, covariate adjustments attenuated or eliminated a substantial proportion of the biomarker-disorder associations, with BMI emerging as the dominant confounder. These findings demonstrate that such confounding structures exist and can be characterized in large cohorts, though specific biomarker-disorder relationships require validation in clinical samples. Conclusions and RelevancePoor reproducibility of biomarkers may not only stem from insufficient biological signal but also from inconsistent handling of confounders. We propose a systematic framework distinguishing technical factors (to be removed), demographic factors (addressed through adjustment or stratification), temporal factors (ideally controlled at design stages), and behavioral factors (requiring explicit causal reasoning). Associations robust to multiple adjustment strategies should be prioritized for clinical biomarker development. Standardized collection protocols, comprehensive covariate measurement, and transparent reporting across models are essential to improve reproducibility and identify biomarkers that reflect genuine illness-related pathophysiology.

Background: Depression is associated with an increased risk of subsequent Parkinson's disease. Neuroimaging studies suggest a neurobiological overlap in mechanisms underlying Parkinson's disease and psychomotor retardation in depression. Our aim was to investigate whether, among individuals with depression, the presence of psychomotor retardation was associated with the development of subsequent Parkinson's disease. Methods: In a retrospective cohort study, electronic healthcare records from individuals diagnosed with depression at age 40 or over in a large mental health service in London, UK were examined for the presence of psychomotor retardation. Linkage to general hospital records was used to ascertain diagnoses of Parkinson's disease between 2007 and 2023. Cox regression was used to compare the hazard of Parkinson's disease in individuals with depression with and without psychomotor retardation. Results: Among 6327 patients with depression, 2402 (38.0%) had psychomotor retardation. The adjusted hazard ratio for development of Parkinson's in those with psychomotor retardation was 1.43 (95% CI 1.02 - 2.01, p = 0.04). Secondary analyses demonstrated a significant difference in psychomotor retardation incidence at least 10 years before Parkinson's diagnosis. Conclusions: Psychomotor retardation in later-life depression is associated with increased risk of subsequent Parkinson's diagnosis over an extended period of time, suggesting that the relationship cannot solely be explained by misdiagnosis. Psychomotor retardation may therefore serve as a marker of prodromal Parkinson's disease.