The British Journal of Psychiatry

BackgroundA study conducted in Norway showed that the association between pupil mental health diagnoses and educational attainment has weakened over time. One possible explanation is that earlier detection of mental health problems in recent years has facilitated earlier treatment, intervention, and educational support that might improve academic outcomes. We investigated whether the weakening association between mental health and attainment could be replicated in England, and explained by earlier age at first diagnosis. MethodsThis was a secondary longitudinal data analysis of de-identified records from a secondary mental healthcare provider in England, which have been linked to the Department for Educations National Pupil Database. We included n=149,841 pupils residing in South East London, born 1993-2003, who completed their end-of-school exams 2009-2019. The main exposure variables were ADHD and internalising disorder diagnosis. In linear regressions, we investigated their associations with Year 11 attainment (typically assessed age 15-16 years), whether this was modified by birth year, and the role of age at first diagnosis. ResultsOn average, ADHD (n=844, 0.6%) and internalising disorder (n=2,523, 1.7%) were associated with lower Year 11 attainment. However, significant interactions between diagnosis and birth year suggested that pupils with these disorders showed increases in standardised exam scores over successive birth cohorts, resulting in a closing attainment gap over time. While age at first diagnosis became younger over the period, this did not confound the observed associations. ConclusionsWe replicated findings from Norway that suggest a narrowing attainment gap between those with and without ADHD and internalising disorder diagnoses. Building on this, we ruled out earlier age of diagnosis as a possible explanation for this phenomenon. With administrative data research growing internationally, we are increasingly able to replicate mental health and education trends in different countries, opening more opportunities for international collaboration.

Background and HypothesisClozapine is the only antipsychotic with protective effects against suicide in schizophrenia (SCZ). Newer third-generation antipsychotics (TGA) have better tolerability and modulate serotonin, dopamine, and N-methyl-d-aspartate neurotransmission pathways implicated in suicide. We aimed to investigate the effects of TGAs on suicide in SCZ. MethodsWe searched seven databases up to December 2023 for SCZ studies that reported suicide data. The primary outcome was suicide deaths and attempts; suicidal ideation was added as a secondary outcome. Random effects meta-analyses quantified suicide risk in randomized controlled trials (RCT) while single proportion meta-analyses assessed longitudinal suicide risk in open label extension trials (OLE). For RCTs, sensitivity analyses were conducted and subgroup analyses explored the impact of dose, drug type, and comparator arm. Study ResultsTwenty articles were included; thirteen excluded higher suicide risk participants. Compared to placebo control, TGAs did not significantly change the risk of primary [RR = 0.65, p = 0.38] or secondary [RR = 0.63, p = 0.15] suicide outcomes. Subgroup and sensitivity analyses were not statistically significant. For OLEs, there was a significant increase in the incidence of primary [Ip = 0.004, p = 0.048] and secondary [Ip = 0.024, p = 0.0013] suicide outcomes, but there was marked study heterogeneity. ConclusionThere is no current trial evidence to show that TGAs significantly impact suicide outcomes in SCZ. The signal from OLEs should be interpreted cautiously due to heterogeneity and requires replication. An effective clozapine alternative is needed for suicide prevention in SCZ.

Background Hospital admissions for mental health (MH) and stress related presentations (SRP; symptoms without a clear medical cause which may be psychosomatic in nature) among children and young people (CYP) have risen over time. Rehospitalisation contributes to service costs, may indicate gaps in community based care, and can also disrupt education and social development. Methods This retrospective cohort study used NHS Hospital Episode Statistics to identify all CYP aged 10 to 25 with >1 MH/SRP related hospital admissions in England between 1 April 2014 and 31 March 2018, with follow up until 31 March 2019. Admissions were classified from ICD10 codes into internalising, externalising, personality, and eating disorders, psychosis, self-harm, substance use, postpartum, or potentially psychosomatic diagnostic groups. Outcomes included 30 day all cause readmission, 1 year all cause readmission, and 1 year MH/SRP-specific rehospitalisation. Time to rehospitalisation, and number of MH/SRP readmissions were also evaluated. Clinical and sociodemographic characteristics associated with rehospitalisation were assessed using regression models, time to rehospitalisation using Kaplan Meier analyses, and diagnostic transitions were visualised using Sankey diagrams. Results Of 492,061 CYP with hospital admission for MH/SRP, approximately one third were rehospitalised within one year. Females, older CYP and those from more deprived areas had higher odds of all cause readmission. The odds of MH/SRP rehospitalisation were highest among those aged 14 to 15 years. Co occurring chronic physical health conditions, personality and eating disorders were associated with higher odds, and shorter time, to readmission. Conclusions Rehospitalisation following MH/SRP admissions is common and socioeconomically patterned among CYP. Targeted discharge planning and continuity of care interventions are needed, particularly for high risk CYP admitted with eating and personality disorders.

BackgroundProlonged waiting times for Child and Adolescent Mental Health Services (CAMHS) leave many young people without structured support while awaiting specialist treatment. Social prescribing has been proposed as a community-based adjunct within CAMHS pathways; however, evidence regarding its safety and clinical impact remains limited. MethodsWellbeing While Waiting was a multi-site non-randomised controlled trial embedded within a hybrid type II implementation-effectiveness evaluation conducted across 11 CAMHS in England. The protocol was prospectively published prior to recruitment (BMC Psychiatry; 10.1186/s12888-023-04758-0). Between May 2023 and March 2025, 558 young people aged 11-18 years referred to CAMHS were enrolled (225 usual care; 333 social prescribing). Primary outcomes were anxiety and depression symptoms, total emotional and behavioural difficulties, and perceived stress. Secondary outcomes included resilience and wellbeing. ResultsNo intervention-related adverse events were observed. On average, participants had 5 sessions with a Link Worker. Compared with usual care, no significant differences were observed in anxiety or depression symptoms. However, participants receiving social prescribing demonstrated significant improvements in total emotional and behavioural difficulties over six months, driven by reductions in conduct difficulties, hyperactivity and peer problems. Significant improvements for those receiving social prescribing were also found for prosocial behaviour and resilience. ConclusionsWithin routine CAMHS pathways, no intervention-related adverse events were observed for social prescribing, and social prescribing was associated with improvements in behavioural and resilience-related outcomes, although not in anxiety or depressive symptoms. Findings suggest social prescribing may offer a valuable adjunct during delayed access to specialist treatment, with effects distinct from symptom-focused clinical therapies.

Background and HypothesisClozapine is the only medication with proven efficacy for treatment-resistant schizophrenia, yet many patients experience delays of several years before initiation. Our aim was to develop and validate a dynamic prediction model for clozapine initiation among patients with schizophrenia trained solely on electronic health record (EHR) data from routine clinical practice. Study DesignEHR data from all adults ([≥] 18 years) with a schizophrenia (ICD10: F20) or schizoaffective disorder (ICD10: F25) diagnosis who had been in contact with the Psychiatric Services of the Central Denmark Region between 1 January 2013 and 1 June 2024 were retrieved. 179 structured predictors were engineered (covering, e.g.,diagnoses, medications, coercive measures) and 750 predictors derived from clinical notes. At every psychiatric hospital visit, we predicted if an incident clozapine prescription occured within the next 365 days. XGBoost and logistic regression models were trained on 85% of the data with 5-fold stratified cross-validation. Performance was evaluated on the remaining 15% of the data (held out) using the area under the receiver operating characteristic curve (AUROC). Study ResultsThe training/test set comprised of 194,234/35,527 hospital visits, distributed on 4928/878 unique patients. In the test set, the best XGBoost model achieved an AUROC of 0.81, sensitivity of 32%, positive predictive value of 23% at a 7.5% predicted positive rate. ConclusionsA dynamic prediction model based solely on EHR data predicts clozapine initiation with high discrimination. If implemented as a clinical decision support tool, this model may guide clinicians towards more timely initiation of clozapine treatment.

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.

BackgroundSexual minority (SM) individuals have worse mental health than heterosexual peers. However, there is no total population-based and national-level evidence on differences in risk of self-harm and suicide by sexual orientation. This study provides the first national population-based estimates in England and Wales. MethodsUsing 2021 Census data linked with hospital records and death registrations, we analysed sexual orientation (SO) differences in: (i) at least one hospital inpatient admission/emergency attendance for intentional self-harm, and (ii) death by suicide. We calculated age-standardised rates per 100,000 people by SO between March 2021 and December 2023, and stratified by sociodemographic, geographical, socioeconomic and health-related variables. We calculated rate ratios for lesbian/gay/bisexual/other SO (LGB+) groups compared with heterosexuals to estimate sexual identity disparities. FindingsOur study population included 28.7 million people (mean age 48.1 years, 53.7% female, 84.2% White) aged [≥]16 years who self-reported their SO in Census 2021 and linked to an NHS number. LGB+ individuals had 2.52 (95% CI 2.48-2.56) times higher risk for self-harm and 2.17 (95% CI 1.98-2.37) times higher risk for suicide than heterosexual people. Relative risk of self-harm was highest for LGB+ females, younger adults, and Black individuals. Relative risk of suicide was highest for LGB+ females, older adults, and Black individuals. InterpretationThis study demonstrates stark inequalities in risk of self-harm and suicide by sexual orientation, consistent across multiple sociodemographic factors. These findings are important for informing government prevention programs and further mental health research. FundingThere was no external funding for this study. Research in contextO_ST_ABSEvidence before the studyC_ST_ABSThe substantial evidence on higher risk for self-harm and suicide in sexual minority groups in the UK (and wider Europe) is impacted by regional samples, younger populations, or surveys limited by smaller numbers precluding analyses by key sociodemographic factors (like sex, ethnic group, socioeconomic indicators, faith, housing situations and geographical indicators) or combining all sexual minority groups together. To date, no study has used total population-based data to examine sexual orientation inequalities in self-harm and suicide and in relation to a range of sociodemographic factors. Added value of this studyTo our knowledge, this is the first study in the UK to provide national population-based estimates of intentional self-harm and suicide by sexual orientation, including intersectional analyses across age, sex, ethnic group, and socioeconomic position. This study used a unique linkage between the census, hospital inpatient data, emergency care records and death registrations from across England and Wales, with a study population of 28.7 million people aged [≥]16 years who self-reported their sexual orientation in Census 2021 and linked to a National Health Service (NHS) number. Implications of all the available evidenceThis research provides national population-level evidence of substantial increased risk for self-harm and suicide among sexual minority individuals, compared with heterosexual individuals. This study also identified key groups of individuals at an increased risk of self-harm and suicide. These findings are important for informing government prevention programs and further research supporting the mental health of sexual minority groups.

BackgroundExternal validations of existing risk models is an efficient step towards potential implementation, obviating the need to develop new models. However, validation in new clinical settings poses several challenges. ObjectiveTo externally validate the OxSATS tool using data from the Oxford Monitoring System for Self-harm in England. OxSATS is a validated tool to predict suicide after self-harm developed using Swedish population registers. MethodsWe selected episodes of self-harm (ICD-10 codes X60-84; Y10-34) by individuals aged 10-64 years who presented to a large regional hospital between 1 January 2000 and 31 December 2018, and were followed up until 31 December 2019. We applied the OxSATS tool to estimate each individuals suicide risk within 12 months after their index self-harm. We assessed model performance using discrimination (Harrells c-index) and calibration measures (calibration plot and the observed-to-expected events ratio, O:E). We assessed the effects of missing predictors on calibration and subsequently recalibrated the model. FindingsWe identified 16,120 individuals who presented to hospital with self-harm, of whom 101 (0.6%) died by suicide in the 12-month follow-up period. The OxSATS model showed good discrimination in external validation (c-index=0.72, 95% CI=0.67, 0.77). Recalibration was required because initial calibration reflected a lower outcome rate in the new data. After recalibration, calibration performance was excellent (O:E=1.00, 95% CI=0.80, 1.20). ConclusionsDespite differences in clinical services and outcome ascertainment, suicide risk models can maintain good predictive performance in new settings. However, recalibration should be considered when applying prediction models in new settings, and the impact of missing predictors should be assessed using sensitivity analyses. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABSSuicide risk is substantially elevated after hospital presentation for self-harm, but most existing risk assessment tools rely on rating scales or binary cut-offs, show limited predictive accuracy, and rarely report calibration. OxSATS is a prognostic model developed using Swedish register data that provides continuous risk estimates and demonstrated good discrimination and calibration in its original setting. External validation in new healthcare systems is essential before implementation, but is often complicated by differences in predictor definitions, missing variables, and outcome prevalence. What this study addsThis study provides the first external validation of OxSATS in an English clinical setting using routinely collected hospital data. The model retained good discrimination but initially overpredicted suicide risk due to a lower baseline event rate and one missing predictor, highlighting the importance of calibration assessment. How this study might affect research, practice or policyFuture research and implementation strategies should routinely incorporate external validation, sensitivity analyses for missing predictors, and local recalibration before clinical or policy adoption.

ObjectiveTobacco and cannabis are the most used substances among individuals at clinical high risk for psychosis (CHR-P), but it remains controversial whether substance use drives symptom exacerbation and psychosis transition, or vice versa. We investigated longitudinal dose-response relationships of tobacco and cannabis use with clinical presentation in a CHR-P population. MethodsData was obtained from the North American Prodrome Longitudinal Study (NAPLS2) CHR-P cohort (n=764). Participants were assessed every 6 months over two years. Substance use frequency, psychiatric symptoms (psychosis, depression, anxiety, and social anxiety), global social and role functioning, and neurocognitive performance were measured. Linear mixed effect models were used to model the relationship between substance use and clinical measurements across visits, and that between baseline use and trajectory of symptoms, functioning, and cognition. ResultsPsychiatric symptoms, functioning, and cognitive performance improved, while tobacco and cannabis use frequency did not change over two years for CHR-P individuals in NAPLS2. Heavier tobacco and cannabis use at current visit predicted worse anxiety at next visit (tobacco: {beta}=0.178, p=0.033; cannabis: {beta}=0.162, p=0.018). Better social functioning predicted heavier tobacco ({beta}=0.178, p<0.001) and cannabis: ({beta}=0.162, p<0.001) use at next visit. We observed a significant baseline cannabis-by-time interaction, where heavier baseline cannabis use predicted slower improvement of negative symptoms ({beta}=0.159, p=0.0017, FDRp=0.0067) and deterioration of role function ({beta}=-0.046, p=0.018). ConclusionsIn CHR-R, current tobacco and cannabis use predicted worse anxiety at future visits. Baseline cannabis use frequency predicts worse clinical trajectory, especially for negative symptoms.

BACKGROUND: Predicting long-term outcomes in first-episode schizophrenia (FES) remains difficult, despite being especially important early in the illness, when timely intervention is most critical. Many potential predictors have been studied, but few are reliable enough to guide early treatment decisions. It also remains unclear how much data from the initial phase of illness is required to improve prognostic accuracy. METHODS: We analysed 68 patients with first-episode schizophrenia (FES) assessed at baseline (V1; mean 0.5 years post-onset, YPO), one-year follow-up (V2; mean 1.2 YPO), and outcome (V3; mean 4.9 YPO). We trained elastic-net models to predict three V3 outcomes-negative symptoms (PANSS Negative factor; Wallwork/Fortgang), global functioning (GAF), and quality of life (WHOQOL-BREF psychological domain)-using either 23 V1 predictors alone or V1 predictors plus V2 data (43 predictors). Performance was evaluated with nested cross-validation on held-out data. RESULTS: Using predictors from the first year (V1+V2), we achieved statistically significant out-of-sample prediction for all three V3 outcomes: PANSS Negative factor (Wallwork/Fortgang) R2=0.22 driven mainly by log(DUP), PANSS Negative at V1/V2, and PANSS Disorganized at V2; WHOQOL-BREF Psychological Health R2=0.22 driven mainly by WHOQOL Psychological Health at V2 and GAF at V2; and GAF R2=0.14 driven mainly by GAF at V2, PANSS Positive at V2, WHOQOL Psychological Health at V2, and hospitalization burden (before V1 and between V1-V2). With baseline-only predictors (V1), only PANSS Negative showed meaningful predictive power (R2=0.15); GAF and WHOQOL-BREF did not outperform the intercept-only baseline. CONCLUSION: In FES, long-term functioning (GAF) and quality of life (WHOQOL-BREF) can not be predicted well from first-episode (V1) measures; at least an additional 1 year of follow-up is needed, implying these outcomes are driven by changes after onset that V1 misses. Negative symptoms differ: they are comparatively stable after initial antipsychotic treatment, and duration of untreated psychosis is their strongest predictor beyond baseline severity-consistent with early biology and treatment timing shaping their level and persistence. These contrasting patterns indicate different outcome phenotypes.

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.

Childhood adversities are common and linked to increased risk of premature mortality, including deaths from accidents in early adulthood. We examined associations between childhood adversity and specific types of lethal accidents using nationwide register data from 1,282,636 individuals in the DANish LIFE course (DANLIFE) cohort born between Jan 1, 1980, and Dec 31, 2001, who did not die or emigrate before age 16. Individuals were classified into five trajectory groups based on annual exposure to 12 adversities across three dimensions from ages 0-15. Accident mortality was categorised into traffic, narcotic and hallucinogenic, other poisoning, and other accidents. Individuals were followed through Dec 31, 2022. Relative and absolute risks were estimated using Cox proportional hazards and Aalen additive hazard models. Compared with the low-adversity group, individuals in one of the childhood adversity groups experienced 4.4 to 33.8 additional accident deaths per 100,000 person-years. The largest relative (HR=13.4 95% CI [9.9-18.6]) and absolute (HD=12.9 95%CI [10.0-15.8]) differences were identified for the high versus low adversity group. High childhood adversity is strongly associated with preventable accident mortality in early adulthood, underscoring the need for structural and social interventions to reduce adversity exposure and related excess mortality.

ABSTRACT Background and aims: Mental and behavioral disorders due to use of tobacco (MBDT) present a critical challenge to global health, yet modifiable lifestyle factors for reducing its risk remain poorly understood. Given that dietary fibre can affect mental health through gut-brain communication, we sought to explore how fibre intake relates to MBDT risks in smokers. Methods: We specifically evaluated the link between dietary fibre intake and MBDT within a smoking population. Utilizing the UK Biobank (UKB) database, we performed cross-sectional (N=19,943) and prospective cohort (N=19,885) evaluations applying logistic and Cox proportional hazards models, respectively. To determine potential causality, two-sample Mendelian randomization (MR) was applied, relying on GWAS summary data derived from the IEU Open GWAS Project and FinnGen repositories. Results: Cross-sectional findings indicated that individuals in the top quartile (Q4) of fibre intake exhibited decreased MBDT risks relative to the bottom quartile (Q1) (OR: 0.32, 95% CI: 0.13-0.79). Over a median observation time of 12.84 years, the prospective evaluation demonstrated a notable inverse correlation (Q4 HR: 0.46, 95% CI: 0.40-0.54). Non-linear modeling via restricted cubic splines uncovered an L-shaped dose-response curve. Furthermore, MR results confirmed a genetically predicted protective causality (IVW OR: 0.68, 95% CI: 0.49-0.95), which remained consistent across sensitivity validations. Conclusions: Among smokers, higher dietary fibre intake is robustly associated with a reduced risk of mental and behavioral disorders due to the use of tobacco, offering a modifiable dietary target for public health interventions.

BackgroundWhile growing evidence implicates sleep-wake and circadian rhythm disturbances (SCRDs) in the onset and course of mood and psychotic disorders, longitudinal studies using objective measures are limited. This clinical cohort study examined whether actigraphy-derived SCRDs (sleep duration, timing, and efficiency) predicted transition to (i) any full-threshold mental disorders; and then specifically: (ii) full-threshold bipolar or psychotic disorders or (iii) other full-threshold (i.e. depressive or anxiety) disorders, in youth accessing mental health care. MethodsActigraphy monitoring was completed for 5-23 days in 250 participants (aged 12-30) presenting to youth-focused early intervention services in Sydney, Australia. Participants were followed longitudinally as part of the Optymise cohort for 6+ months (up to 8 years; median 2.5 years). Logistic regression and Cox proportional hazard models estimated associations between SCRDs and illness progression, after controlling for relevant baseline clinical and demographic covariates (e.g., age, sex, social and occupational functioning, mania-like and psychotic-like experiences, medication use). ResultsLonger sleep duration at baseline predicted higher odds of transition (OR = 2.23 [95%CI = 1.38-3.74]), and shorter time-to-transition (HR = 2.05 [95%CI = 1.23-3.40]) to full-threshold bipolar or psychotic disorders. This effect remained significant after controlling for clinical covariates. Later sleep midpoint predicted transition to any full-threshold mental disorder (OR = 1.46 [95%CI = 1.02-2.17]) at the uncorrected significance level. ConclusionsExcessive sleep duration may represent an early marker of vulnerability for progression to severe mental illness. Findings support the prognostic utility of objective measures of SCRDs to guide indicated prevention and early intervention.

Importance: Suicide is a leading cause of death in the United States with risk strongly influenced by Interpersonal trauma, contributing to treatment resistance and clinical complexity. Objective: To assess clinical and genetic factors in individuals who died from suicide, with and without interpersonal trauma exposure. Design: Individuals who died from suicide with and without trauma were compared in a retrospective case-case design. Prevalence of 19 broad clinical categories was assessed between groups. Results directed selection of 42 clinical subcategories, and 40 polygenic scores (PGS) for further assessment. Multivariable logistic regression models, adjusted for critical covariates and multiple tests, were formulated. Models were also stratified by age group (<26yo and >=26yo), sex, and age/sex. Setting: A population-based evaluation of comorbidity and polygenic scoring in two suicide death subgroups. Participants: A total of 8 738 Utah Suicide Mortality Research Study individuals (23.9% female, average age = 42.6 yo) who died from suicide were evaluated, divided into trauma (N = 1 091) and non-trauma exposed (N = 7 647) individuals. A subset of unrelated European genotyped individuals was also assessed in PGS analyses (Trauma N = 491; Non-trauma N = 3 233). Exposures: Trauma is here defined as interpersonal trauma exposure, including abuse, assault, and neglect from International Classification of Disease coding. Main Outcomes and Measures: Prevalence of comorbid clinical sub/categories and PGS enrichment in trauma versus non-trauma exposed suicide deaths. Results: Overall, trauma-exposed individuals died from suicide earlier (mean age of 38.1 yo versus 43.3 yo; P <0.0001) and were disproportionately female (38% versus 21%, OR = 3.3, CI = 2.9-3.8). Prevalence of asphyxiation and overdose methods, prior suicidality, psychiatric diagnoses, and substance use (OR range = 1.3-3.7) were elevated in trauma exposed individuals who died from suicide. Genetic PGS were also elevated in trauma-exposed individuals who died from suicide for depression, bipolar disorder, cannabis use, PTSD, insomnia, and schizophrenia (OR range = 1.1-1.4) with ADHD and opioid use showing uniquely elevated PGS in trauma exposed males (OR range = 1.2-1.4). Conclusions and Relevance: Results demonstrated multiple convergent lines of age- and sex-specific evidence differentiating trauma-exposed from non-trauma exposed suicide death. Such findings suggest unique biological backgrounds and may refine identification and treatment of this high-risk group.

Background The ageing of incarcerated populations is accelerating across high-income countries, yet dementia remains absent from routine correctional mental health statistics. We investigated whether correctional data systems in Japan, the United States, the United Kingdom, and Australia are structurally capable of detecting dementia in their prison populations. Methods We conducted a cross-national descriptive analysis of publicly available, aggregate-level correctional data. Japanese data comprised all newly admitted sentenced prisoners from 2006 to 2024 (approximately 390,000 individuals) from the Ministry of Justice Correctional Statistics Annual, including mental disorder classifications and CAPAS-derived work aptitude scores (used as a proxy for cognitive functioning; not clinical IQ measurements). US data were drawn from the Bureau of Justice Statistics Survey of Prison Inmates (2016). UK data were obtained from the Ministry of Justice Offender Management Statistics Quarterly (2015-2025). Australian data were sourced from the Australian Institute of Health and Welfare National Prisoner Health Data Collection (2022, n = 371). All analyses were descriptive; no inferential statistics were conducted. Findings Three distinct mechanisms rendered dementia statistically invisible across all four countries. First, in the United States and Australia, reliance on self-report instruments produced a paradox in which self-reported mental disorder prevalence declined with age: among US state prisoners, reported prevalence fell from 44.9% in the 35-44 age group to 31.9% among those aged 65 and older - the opposite of community epidemiological patterns. Second, in Japan - the only country with systematic cognitive assessment at prison admission - 35.0% of female theft offenders had work aptitude scores below 70, yet the classification system contains no dementia category; 43-52% of all detected mental disorders were absorbed into a residual "other" category even after a 2023 classification revision that added four new diagnostic categories but not dementia. Third, the United Kingdom lacks routine mental health prevalence data collection in prisons altogether. None of the four countries includes dementia as a standard correctional classification category. Interpretation Correctional mental health statistics across four high-income countries are structurally incapable of detecting dementia - not through clinical ignorance but by design: systems built for younger populations that have not been updated as prison demographics have changed. Japan's ageing female theft offender profile (39.4% aged 60 or older, 35.0% with low cognitive scores) represents a potential sentinel population for undetected cognitive impairment. Targeted interventions - cognitive screening at admission in the United States and Australia, introduction of a dementia classification category in Japan, and routine mental health data publication in the United Kingdom - are feasible with existing infrastructure. As prison populations continue to age, the statistical invisibility of dementia constitutes an escalating failure of health surveillance with direct consequences for clinical care, sentencing, and human rights.

BackgroundThe prevalences of suicidal ideation (SI) and suicide attempt (SA) are influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate genetic liability for suicidality. MethodsUsing data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime SI or SA. We also evaluated whether alcohol use disorder (AUD) mediated these associations and whether adverse childhood experiences (ACEs) moderated the direct and indirect pathways. ResultsAlthough there were significant direct associations of the SA PGS with SA (AFR: b = 0.36, SE = 0.01; EUR: b = 0.17, SE = 0.01; both ps < 2e-16), the SI PGS did not predict SI (p > 0.55). AUD mediated SA genetic risk (average causal mediation effect (ACME): AFR = 0.01, 95% CI [0.01-0.01]; EUR = 0.02, 95% CI [0.01-0.02]; both ps < 2e-16). Moderation analyses indicated that indirect effects were attenuated by ACEs score ({Delta}ACME: AFR = 0.02, p < 2e-16; EUR = 0.01, p = 0.03). There was neither mediation nor moderated mediation for SI. ConclusionsGenetic liability to SA operates partly through AUD, particularly among individuals with lower childhood adversity. Under higher adversity, alternative pathways to SA likely predominate. These findings highlight the need to consider distinct etiological pathways to the development of suicidality and the relevance of AUD as a modifiable target for suicide prevention among individuals at high genetic liability.

BackgroundAt present, there are no approved pharmacological treatments for people at clinical high risk for psychosis (CHR-P). We sought to assess the acceptability of cannabidiol (CBD): a promising candidate treatment for this population. MethodsCHR-P individuals completed a survey which assessed their views on the acceptability of CBD, its expected effectiveness and side effects, and on formulation preferences. ResultsThe sample comprised 55 CHR-P individuals (24.3 years and 69% female). Most (91%) were familiar with CBD, and had previously used cannabis (64%), and around half (42%) had tried over-the-counter CBD. 75% were willing to take CBD as an intervention for mental health problems. Most participants anticipated fewer side effects with CBD than with existing medications, and preferred tablet or capsule formulations over liquids. DiscussionCBD is perceived as a highly acceptable treatment among CHR-P individuals.

BackgroundThe UK has the fourth highest estimated prevalence globally of maternal alcohol consumption during pregnancy (41%). It is therefore important to understand the long-term impacts of prenatal alcohol exposure (PAE) by examining its impact on the development of adolescent multiple risk behaviours (MRBs) which may increase morbidity and premature mortality across the life-course. MethodsUsing Avon Longitudinal Study of Parents and Children (ALSPAC) cohort data with multiple imputation (n=6,752), we examined the impacts of infrequent, frequent, and binge PAE groups on the development of seven MRBs at 16 years old, encompassing substance misuse, risky sexual behaviour and antisocial behaviour. Data were analysed using multiple regression, using q-statistics to adjust for multiple comparisons. ResultsAdolescents with infrequent and frequent PAE were more likely to develop hazardous alcohol use at 16 years old compared to those without PAE, with the strongest association being for the frequent group (adjusted odds ratio (aOR) 1.45 [1.19-1.76], p<0.001, q-value=0.005). Adolescents exposed to binge drinking prenatally had an increased risk of engaging in underage sexual intercourse (aOR 1.34 [1.09-1.64], p=0.005, q-value=0.044). Binge drinking predicted a higher total MRB score (Coefficient = (+0.21 [+0.08 to +0.33], p=0.001, q-value=0.017). ConclusionsThis study supports the UK Chief Medical Officers Low Risk Drinking Guidelines that the safest approach if pregnant, or if there is a possibility of becoming pregnant, is to avoid drinking alcohol, with the more alcohol consumed during pregnancy the greater the risks of long-term harm to the baby. Given the findings that PAE may increase the risk of adolescent hazardous alcohol use and risky sexual behaviour, this study highlights the need for further research to understand the intergenerational effects of PAE.

BackgroundLipidomic alterations have been reported across schizophrenia (SCZ) and bipolar disorder (BD), but findings are heterogeneous and often overlap across diagnoses, limiting diagnostic specificity. Associations between lipid profiles and illness severity have also been inconsistent when assessed using single symptom scales, raising the possibility that unidimensional measures fail to capture biologically relevant variation. Whether plasma lipidomic alterations relate to multidimensional psychosis severity, and how they relate to polygenic liability, remains unclear. MethodsWe examined associations among psychiatric and cognitive polygenic risk scores (PRS), plasma lipidomics (361 species across 16 classes), and a machine-learning-derived severe psychosis probability score in a transdiagnostic cohort of individuals with SCZ or BD (PRS n=1,320; lipid subset n=428). Regression and lipid class enrichment analyses tested severity associations. Mediation and canonical correlation analyses assessed integrated genetic-lipid-severity relationships. ResultsSCZ-PRS (positive), BD-PRS (negative), and educational attainment PRS (negative) showed modest associations ({beta} = |0.02|) with severe psychosis probability. Lipid class enrichment analysis identified nine classes associated with severity, including increased sphingolipids (dSM, dCer), phosphatidylcholines (PC), triacylglycerides (TAG), and phosphatidylethanolamine plasmalogens (PE-P), alongside decreased phosphatidylcholine plasmalogens (PC-P). Most lipid class associations were robust to adjustment for diagnosis and medication. No significant mediation or shared multivariate genetic-lipid structure was observed. ConclusionsPlasma lipidomic variation tracks multidimensional psychosis severity across diagnostic boundaries. These findings suggest that lipidomic alterations may reflect transdiagnostic biological processes linked to illness burden that are not fully captured by categorical diagnoses, single symptom scales, or common-variant polygenic risk.