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Background The last 40 years have seen a substantial improvement in overall survival from cancer in children and young people. There is limited information on psychiatric wellbeing in female survivors of cancer at a young age. Objective In this 40-year population-based linkage study, we set out to determine the incidence of first psychiatric admission compared with a non-exposed age-matched control. Methods Scottish cancer registry records from 1981 to 2012 were linked to psychiatric admissions, maternity and death records from January 1981 to September 2018 using the unique personal Community Health Index number allocated to each person in Scotland. For each exposed subject, three age and deprivation matched controls from the population were selected. The primary exposed group was all females with a cancer diagnosis at age <25 years and no previous pregnancy and no psychiatric admission before cancer diagnosis. The main outcome measure is admission to a psychiatric hospital with a mental health diagnosis. Findings Female cancer survivors had a significantly lower cumulative incidence of first psychiatric admissions than matched controls over the 38 years of follow-up for the cohort (p<0.05). The relative risk of a first psychiatric admission at 25 years from cancer diagnosis was 0.72 (0.56–0.89). Conclusion Overall, we have shown that young cancer survivors are less likely than age-matched controls to have a psychiatric admission after cancer diagnosis. In particular, psychiatric admissions for mood disorders, neuroses, personality disorders and substance use are significantly less likely in the cancer survivors. Clinical implications The experience of cancer treatment and survival in young females may reduce the risk of psychiatric admission in later life.

Background Epistemic trust describes the capacity to appropriately identify others as reliable and relevant sources of information, an ability closely linked to attachment and social learning. Epistemic disruption can manifest as heightened suspicion (mistrust) or excessive reliance (credulity) vis-à-vis others, affecting mentalizing abilities and increasing vulnerability to psychopathology and maladaptive traits. These interdependent and multidirectional dynamics are pivotal to therapeutic learning, and thus to therapeutic change. Objective This study examined associations between epistemic trust and disruption, markers of psychopathology, therapeutic relationship quality and treatment-seeking behaviour. Method A naturalistic sample of 912 participants, recruited via a mental health app, completed the Epistemic Trust, Mistrust and Credulity Questionnaire, along with self-reports capturing internalising symptoms, personality functioning, maladaptive traits and the perceived therapeutic relationship within the previous 6 months. Treatment-seeking behaviour and the number of sessions utilized in the past year were further explored—both in psychotherapeutic and psychiatric contexts. Findings Epistemic mistrust and credulity showed consistent relationships with markers of psychopathology. Higher epistemic (mis)trust correlated with more positive (negative) ratings of various aspects of the therapeutic relationship, including genuineness, realism, expectations, congruence and responsivity—over the past 6 months. Epistemic trust positively predicted the amount of psychotherapy sessions, while epistemic mistrust negatively predicted treatment-seeking, both controlled for personality dysfunction. Epistemic credulity predicted mental health app use—all assessed retrospectively (past year). Conclusion The results encourage further in-depth exploration of trust-related aspects of the therapeutic alliance and investigation of mechanisms of change in therapeutic processes that may facilitate the transition from mistrust and credulity to trust. Clinical implications Even though the magnitude and direction of effects remain to be clarified, patients with epistemic mistrust may enter a self-reinforcing cycle of reduced openness and ineffective mentalizing, potentially impacting therapeutic effectiveness. Interventions targeting epistemic disruption and impaired personality functioning seem to be crucial for improving therapeutic outcomes, including psychopharmacological treatment effectiveness.

Background Many countries have introduced restrictive smartphone policies in schools, aiming to improve adolescent health and educational outcomes. However, whether these policies represent value for money to schools remains unclear. Objective The aim of this study was to estimate the costs and quality of life and mental well-being outcomes associated with restrictive and permissive phone policies in secondary schools in England, and conduct an economic evaluation to determine whether restrictive phone policies are cost effective for schools. Methods A cost–utility analysis was conducted as part of a cross-sectional study on school smartphone policies in England (SMART Schools), comparing schools with restrictive (recreational phone use not permitted) and permissive (recreational phone use permitted) policies. Outcomes were valued using quality-adjusted life years (QALYs) and mental well-being adjusted life years (MWALYs). Costs were estimated from the school’s perspective and comprised staff time spent on policy implementation. Mixed effects and linear regression models were used to estimate incremental differences in outcomes and per pupil costs. Findings 815 pupils (aged 12–15) from 20 schools (13 restrictive, 7 permissive) were included in a complete case analysis. Differences between restrictive and permissive schools in incremental QALYs (0.009, 95% CI –0.014 to 0.032) and MWALYs (–0.004, 95% CI –0.044 to 0.036) were minimal. Time implementing and enforcing policies was equivalent to 3.1 FTE staff in restrictive and 3.3 FTE staff in permissive schools. The incremental difference in per pupil school year cost was –£94 (95% CI –£229 to £41). The cost-effectiveness acceptability curve indicated a 90% probability of restrictive policies being cost effective at a threshold of £20 000 and £30 000 per QALY. Conclusions Restrictive school policies were associated with minimal differences in quality of life or mental well-being of pupils. However, they may offer some cost savings to schools by reducing staff time spent managing phone-related activities. Clinical implications School policies and practices require development to address the significant amount of time teachers spend managing phone use.

Background Currently available cardiovascular disease (CVD) risk prediction tools may underestimate the risk in individuals with schizophrenia. Objective To develop and externally validate 5-year CVD risk prediction models for people with schizophrenia using large-scale register data in Sweden and Denmark with a machine learning (ML) approach. Methods Individuals with a diagnosis of schizophrenia, aged 30 and older and without prior CVD, were followed for up to 5 years. We investigated whether adding additional health-related and socio-demographic predictors to the established CVD risk factors improved predictions and compared ML models with logistic regression. External validation was performed across countries. Findings A lasso penalised logistic regression including additional predictors achieved the highest predictive performance, both on Swedish and Danish data, while complex ML models with interaction terms did not provide additional improvements. The area under the receiver operating characteristic curve (AUC) on the internal validation data was 0.745 (95% CI (0.742 to 0.749)) in the Swedish model, and 0.722, 95% CI (0.719 to 0.726) in the Danish model. External validation showed similar performance, yielding an AUC of 0.746, 95% CI (0.741 to 0.751) using the Danish model on the Swedish data, and an AUC of 0.720, 95% CI (0.712 to 0.726) using the Swedish model on the Danish validation data. Conclusions Incorporating additional health-related information, such as psychiatric comorbidities and medication use, improved 5-year CVD risk prediction for people with schizophrenia in both countries. Clinical implications The models can be deployed between Denmark and Sweden without loss of performance compared with training a model on each country.

Objectives Bipolar disorder (BD) often begins in adolescence, a period marked by dynamic neurodevelopment. However, the neurobiological basis from genetic risk and subthreshold symptoms to diagnosed BD remains unclear. Methods We conducted a cross-sectional analysis using data from the Recognition and Early Intervention of Prodromal Bipolar Disorders cohort (NCT01863628), including 392 participants aged 12–25 years with a balanced sexual distribution, stratified into five groups: offspring of patients with BD with (OBDs, n=48) or without (OBDns, n=62) subthreshold symptoms, individuals without BD family history but with subthreshold symptoms (nOBDs, n=63), patients diagnosed with BD (n=133) and healthy controls (HCs, n=86). Cortical thickness relative to HC was assessed using high-resolution T1-weighted images and FreeSurfer V.7.3.2. Gene expression patterns were derived from the Allen Human Brain Atlas, and partial least squares regression, along with gene enrichment analyses, were applied to link cortical alterations with underlying transcriptomic profiles. Findings Cross-sectional analyses revealed graded cortical thickness differences across the BD risk spectrum, with patients with BD showing the most pronounced deviations and high-risk individuals with subthreshold symptoms displaying intermediate features relative to HCs. Cortical changes were significantly associated with spatial gene expression patterns, particularly in genes involved in mitochondrial ATP production, oxidative phosphorylation and synaptic signalling. Gene set enrichment revealed that BD-specific cortical thinning correlated with downregulation of excitatory synaptic pathways and excitatory neuron-related gene expression. Conversely, high-risk individuals exhibited upregulation of both excitatory and inhibitory neuronal markers. Developmental transcriptomic enrichment further linked significant genes to mid-childhood and adolescence. Discussion By identifying distinct transcriptomic signatures associated with cortical thinning at different stages, our findings underscore the potential of transcriptomic markers for early detection and intervention in BD. Clinical implications The findings highlight the potential for using transcriptomic markers for early detection and intervention, suggesting that identifying these markers could lead to improved outcomes for at-risk adolescents. This research has the potential to inform clinical practices and policies aimed at early screening and preventive strategies for BD.

Background Non-suicidal self-injury (NSSI) among adolescents is linked to adverse outcomes for youth and their families. While parental involvement is considered essential in treating adolescent NSSI, the effects on parents remain unclear. Objective To evaluate if Internet-delivered Emotion Regulation Individual Therapy for Adolescents (IERITA) adjunctive to treatment as usual (TAU) is superior to TAU alone in improving parental coping with adolescents’ negative emotions, the durability of potential effects and whether reductions in parents’ minimising of their adolescent’s emotions mediate adolescent outcomes. Methods 166 adolescents with NSSI disorder (93% female; mean (SD) age=15.0 (1.2) years) and their parents (83% female; mean (SD) age=46.5 (5.1) years) were randomised to IERITA plus TAU (n=84) or TAU-only (n=82). IERITA is a 12-week, therapist-guided emotion regulation behavioural therapy, including both adolescents and parents. In parallel to the adolescent, parents participate in a separate internet-delivered course designed to provide skills for understanding and supporting their adolescent. The outcomes were parental coping measured by the Coping with Children’s Negative Emotions Scale-Adolescent version, including minimisation (primary outcome), distress, punitive and expressive encouragement responses at baseline, post-treatment (primary endpoint) and 3 months post-treatment. Parental minimisation was tested as a mediator of adolescent NSSI absence and emotion regulation difficulties. Findings There were statistically significant treatment effects on parental minimisation and distress responses at post-treatment and 3 months post-treatment, and punitive responses at 3 months post-treatment, favouring IERITA. Parental minimisation did not mediate adolescent NSSI absence or emotion regulation difficulties. Conclusion IERITA shows promise for supporting parents of youth with NSSI. Further studies are needed to understand how parental improvement may impact youth with NSSI. Clinical implications Online family treatment for NSSI can improve how parents handle their adolescents’ emotions. Trial registration number NCT03353961.

Background Severe anorexia nervosa (AN) represents a subgroup of individuals with AN with prolonged illness duration and poor prognosis. Previous research has reported increased medication use in AN, but prescription patterns in severe AN remain unexplored. Objectives This study aimed to: (1) compare medication prescriptions between individuals with severe and less-severe AN; (2) explore the heterogeneity of prescription patterns among individuals with severe AN across different comorbidity profiles. Methods Using Danish registers, this cohort study included 7654 individuals diagnosed with AN. We assigned cases to severe or less-severe groups based on their AN Register-based Severity Index scores. First, we examined trajectories of medication prescriptions and compared patterns between groups using logistic regression models. Second, common comorbidity profiles among individuals with severe AN were identified by latent class analysis for further between-group comparisons. Sensitivity analyses were conducted to test alternative definitions of severe AN. Findings Compared with individuals with less-severe AN, those with severe AN were more likely to be prescribed various medications, including drugs targeting alimentary tract (OR 1.4, 95% CI 1.3 to 1.6), cardiovascular drugs (OR 1.1, 95% CI 1.0 to 1.3), analgesics (OR 1.2, 95% CI 1.1 to 1.3) and psychotropic drugs (OR 2.4, 95% CI 2.1 to 2.7). Notably, this pattern persisted even among individuals without diagnosed comorbidities. Within the severe group, five clusters with distinct comorbidity profiles emerged, and we consistently observed greater prescription rates than in the comorbidity-free cluster. Sensitivity analyses confirmed that our severity classification reliably distinguished severe from less-severe AN across multiple definitions. Conclusion These findings indicate that severe AN is associated with substantially higher prevalence of prescribed medications, while specific comorbidity patterns further influence prescribing patterns. This diverse and prolonged pharmacological treatment in severe AN reflects the complexity of clinical management in this population. Clinical implications Considering the widespread medication prescription in severe AN despite the lack of specific approved pharmacotherapy for the disorder, evidence-based treatment guidelines are urgently needed. Clinicians should recognise the substantial heterogeneity in severity and comorbidity burden within this population and develop comprehensive and specialised treatment strategies that evaluate risks and treatment needs across all individuals with AN, irrespective of comorbid conditions.

Background Postpartum depression (PPD) remains vastly underdiagnosed, and its clinical heterogeneity is not well understood. Diagnosis codes in electronic health records (EHRs) alone may not identify all PPD cases, highlighting a need for novel detection approaches. Objective To develop a transformer-based natural language processing (NLP) method to identify patients with PPD from clinical notes in EHRs and to examine demographic and clinical heterogeneity among identified cases. Methods Clinical notes from 64 426 patients who gave birth between 2010 and 2023 at a major US academic medical centre were used to develop and evaluate the NLP method. By augmenting the NLP output with International Classification of Diseases (ICD-9/10) diagnosis codes, three subgroups of individuals with PPD were identified: patients identified by ICD only (PPD-ICD), NLP only (PPD-NLP) and both ICD and NLP (PPD-BOTH). Demographics, mental health and substance use disorders (SUDs), antidepressant treatment, behavioural therapy and healthcare utilisation were compared across PPD subgroups and a non-PPD control group. Longitudinal associations of depression and anxiety were also examined. Findings The NLP method identified an additional 29.6% of patients whose clinical notes indicated symptoms suggestive of PPD but who lacked an ICD diagnosis. Significant variation was observed among PPD subgroups in comorbid psychiatric disorders, SUDs, treatment patterns and healthcare utilisation. During the 24 months post-delivery, the PPD-BOTH subgroup exhibited the highest rates of anxiety disorder diagnoses (vs PPD-ICD: OR 1.69, 95% CI 1.49 to 1.93; vs PPD-NLP: OR 4.46, 95% CI 3.82 to 5.22), antidepressant prescriptions (vs PPD-ICD: OR 1.95, 95% CI 1.71 to 2.22; vs PPD-NLP: OR 5.98, 95% CI 5.11 to 7.01) and mental health outpatient visits (vs PPD-ICD: OR 1.45, 95% CI 1.24 to 1.7; vs PPD-NLP: OR 4.94, 95% CI 3.9 to 6.31), suggesting higher symptom severity (all p<0.001). Comorbid depression and anxiety diagnoses were most prevalent during the postpartum period and declined over time. Conclusions Augmenting NLP-based identification with ICD codes yielded more individuals with distinct demographic and clinical profiles, demonstrating the method’s ability to improve case detection and characterise heterogeneity. Clinical implications Given that PPD is underdiagnosed and undertreated, this novel approach demonstrates further potential for NLP in healthcare settings to capture more cases, enabling earlier and more personalised interventions that reach patients who may otherwise be overlooked.

Background Suicidal behaviour shows notable sex differences, and understanding whether genetic factors contribute to these differences is critical for identifying at-risk individuals and prevention. Objective We aim to investigate the genetic contribution to suicide attempts and examine whether genetics account for sex differences in incidence. Methods This population-based cohort study includes 3.1 million individuals born 1963–1998 and followed through Swedish National Registers, including hospitals and specialist outpatient diagnoses and cause of death data. Suicide attempts were identified using ICD codes, indicating intentional self-harm, self-harm using lethal methods or leading to hospitalisation, or resulting in death. Familial aggregation, coaggregation, pedigree heritability and genetic correlations were estimated using genealogical data. For sex-specific analyses, we examined mother–daughter, female sibling, father–son and male sibling pairs, separately. Findings Suicide attempts were more common among females than males (3.3% vs 2.6%). In both sexes, risk aggregated within families (ORs ranged 1.6–3.4 across relative types) and was higher in first-degree than second-degree relatives. Familial aggregation was stronger in females than in males, and in same-sex first degree relatives compared with cross-sex pairs. Pedigree heritability was 41.9% (95% CI 36.0 to 48.4%) and did not differ significantly by sex (female 51.4% (95% CI 40.1% to 58.6%), male 45.1% (95% CI 32.3% to 52.5%), Bootstrap p value 0.40). Suicide attempt showed moderate to high pedigree genetic correlations with psychiatric disorders, strongest with substance use disorders (SUD, rg=0.85 (95% CI 0.83 to 0.96)), with no significant sex differences. The genetic correlation between female and male suicide attempts was high (0.85 (95% CI 0.80 to 0.99)), suggesting a substantial genetic overlap. Conclusions Suicide attempt has a moderate heritable component that largely overlaps between females and males and with other psychiatric disorders, particularly SUD. Stronger familial aggregation in females and in same-sex pairs highlights the potential role of sex-specific environmental or social factors. Future research should focus on non-genetic contributors and their potential interaction with genetic factors to better understand and address sex disparities in suicidal behaviour Clinical implications Genetic risk for suicide attempt is substantial but does not fully explain sex differences in incidence. Clinicians should, therefore, consider non-genetic, including sex-specific environmental and social factors, alongside family history and psychiatric comorbidity when assessing suicidal risk.

Background Undisturbed circadian rhythms of rest/activity are crucial to health and well-being. There is growing evidence to suggest that circadian rhythm disruptions are also associated with adverse mental health outcomes (and vice versa), but important questions about the relationship between circadian rhythms and mental health remain unanswered. Objective To determine future priorities for research in the area of mental health and circadian rhythms, a James Lind Alliance Priority Setting Partnership exercise in collaboration with a steering group comprising individuals with lived experience, carers and clinicians was undertaken. Methods An initial survey among UK residents provided a set of 964 questions supplied by 247 respondents (227 lived experience, 44 carers (including 40 carers with lived experience), 41 clinicians (including 37 clinicians with lived experience)). Responses were processed into 171 summary questions by the steering group. Reviews of published research and existing clinical guidelines reduced this to 63 unanswered summary questions. A ranking survey of these 63 questions asked respondents to select their 10 most important research questions, from which the most highly ranked would be taken to the final stage. This was completed by 222 respondents (200 lived experience, 33 carers (including 29 carers with lived experience), 38 clinicians (including 30 clinicians with lived experience)). Findings In a final face-to-face workshop, 19 individuals, including individuals with lived experience, carers and clinicians, discussed and ranked a list of questions to produce a ranking of the top 25 research questions/priorities, with a particular focus on the Top 10. Discussion The final research questions are presented to inform researchers and funding bodies when setting future research priorities across the fields of mental health and circadian rhythms. Clinical implications Addressing the priorities identified here should lead to greater understanding of the relationships between mental health and circadian rhythms and will have longer-term impacts on research, healthcare innovation and public health policy.

Background Clozapine is highly effective for treatment-resistant schizophrenia but has been associated with an increased risk of agranulocytosis. As a result, until 2025, the Food and Drug Administration required patients receiving clozapine to undergo regular blood testing to monitor for neutropenia as part of a Risk Evaluation and Mitigation Strategy (REMS) programme. Objective This study sought to compare the risk of neutropenia-related hospitalisations between clozapine and olanzapine initiators. Methods The study cohort was nested in claims data from Medicaid and two commercial health insurance databases and consisted of adults initiating clozapine or olanzapine who had a recorded diagnosis of schizophrenia or schizoaffective disorder and ≥1 dispensing of a different antipsychotic in the 6 months before initiation. Propensity score matching (1:1) was used to mitigate confounding. The primary outcome was hospitalisation with a neutropenia diagnosis in the primary position. Both as-treated and intention-to-treat analyses were implemented. Findings After propensity score matching, there were 16 873 initiators in each group. At 6 months postinitiation, there were 12 neutropenia-related hospitalisations among the clozapine cohort (incidence rate: 2.21 per 1000 person-years; 95% CI 1.25 to 3.89) and <11 among the olanzapine cohort (0.18; 95% CI 0.03 to 1.29), corresponding to an incidence rate ratio (IRR) of 12.18 (95% CI 1.58 to 93.71). The IRRs were 5.77 (95% CI 1.29 to 25.76) at 1 year, 5.50 (95% CI 1.23 to 24.55) at 2 years and 5.40 (95% CI 1.21 to 24.13) at 3 years postinitiation. Associations remained but were attenuated in intention-to-treat analyses. Conclusions Clozapine initiators had an elevated risk of neutropenia-related hospitalisation, especially during the first 6 months of treatment, although the absolute risk was low. Clinical implications Despite removal of the REMS programme, it is important for prescribers to monitor patients for neutropenia after initiating clozapine.

Background Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) often coexist. ADHD complicates the course of disease in SUD. While recommended in guidelines, ADHD medication for those with comorbid SUD remains controversial. Objective This study aims to explore how comorbid SUD affects ADHD medication discontinuation and reinitiation in individuals with ADHD. Methods Using a matched cohort design, we identified 9283 individuals with ADHD and SUD in Sweden between 2006 and 2020, who had ongoing ADHD medication at the time of their first SUD-related event. Controls with ADHD medication but no SUD (n=46 401) were matched 5:1 on sex and birth year. HRs for treatment discontinuation within 1 year from first SUD, and for treatment reinitiation within 1 year from the first discontinuation, were estimated using stratified Cox models. Findings Individuals with ADHD and SUD were nearly two times as likely to discontinue ADHD treatment within 1 year (HR: 1.99, 95% CI 1.92 to 2.07) and less likely to re-initiate ADHD treatment (HR: 0.82, 95% CI 0.76 to 0.89) compared with controls. Several factors, including male sex, adolescent to young adult age and lower stimulant medication dose, were associated with increased risk for treatment discontinuation, but only adolescent to young adult age was significantly associated with treatment reinitiation in those with ADHD and SUD. Conclusions The results suggest less treatment continuity and access for those with ADHD and comorbid SUD. Clinical implications Treatment providers need to consider the specific needs of individuals with ADHD and comorbid SUD, especially in young males, to improve treatment outcomes for vulnerable groups.

Background Comorbid attention-deficit/hyperactivity disorder (ADHD) increases the burden in bipolar disorder (BD). Concerns about the risk/benefit balance of ADHD treatment have been raised. Objective This study aimed to investigate the association between hospital admissions and add-on ADHD medications to antipsychotics and/or mood-stabilisers (APs/MSs) compared with AP/MS alone in BD. Methods Individuals with BD prescribed ADHD medications in Sweden during 2006–2021 were identified from national registers of inpatient care, specialised outpatient care, sickness absence and disability pension. ADHD treatment was defined as stimulants (mostly methylphenidate and lisdexamfetamine, rarely amphetamine, dexamphetamine) and non-stimulants (atomoxetine, modafinil). Add-on ADHD treatment to concomitant AP/MS was compared with treatment periods with AP/MS without ADHD treatment, using within-individual models where individuals acted as their own control. Adjusted HRs (aHRs) and CIs (95% CIs) were calculated for the primary outcome of psychiatric hospitalisation, and for the secondary outcomes: substance-use-related, somatic or mania-related hospitalisations, and all-cause hospitalisation/mortality. Results Altogether, 17 971 individuals (mean age=32.0±11.6 years, males=37.6%, ADHD=88.9%, follow-up=8.9±4.4 years) with BD who used any ADHD treatment were included. compared with the use of AP/MS alone, add-on stimulant use was related to a lower risk of psychiatric hospitalisations (aHR=0.89, 95% CI 0.85 to 0.93), substance-related hospitalisations (aHR=0.75, 95% CI 0.70 to 0.81) and all-cause hospitalisations/mortality (aHR=0.90, 95% CI 0.87 to 0.93), but was not associated with increased risk for somatic (aHR=1.00, 95% CI 0.90 to 1.12) or mania-related hospitalisations (aHR=0.93, 95% CI 0.72 to 1.20). Of commonly used specific ADHD medications, add-on lisdexamfetamine (aHR=0.81, 95% CI 0.75 to 0.87) and methylphenidate (aHR=0.92, 95% CI 0.88 to 0.97) were associated with decreased risk of psychiatric hospitalisations while add-on atomoxetine was not. Findings on substance-use-related hospitalisations were significant only for stimulants, specifically lisdexamfetamine (aHR=0.70, 95% CI 0.61 to 0.79) and methylphenidate (aHR=0.80, 95% CI 0.74 to 0.86). Conclusions Among individuals with BD who received ADHD medications, add-on lisdexamfetamine and methylphenidate were associated with lower risks of psychiatric and substance-use-related hospital admissions, compared with AP/MS use alone. No significant association was found between ADHD medication use and mania-related hospitalisations or somatic admissions when these medications were used together with AP/MS. Larger samples are needed to reach adequate statistical power and conclusive findings on atomoxetine, dexamfetamine and modafinil. Clinical implications The findings of this study suggested that the treatment of comorbid ADHD could be considered after adequate mood-stabilisation in patients with BD.

Background Individuals with mental disorders face excess morbidity and premature mortality. Accelerated ageing has been proposed as a contributing mechanism but population-scale evidence across diverse diagnoses is limited. Objective To examine whether metabolomic ageing differs across mental disorders and whether associations vary by sex, age group and genetic liability. Methods Using plasma metabolomic profiles from UK Biobank participants, we applied a metabolomic ageing clock (MileAge) to estimate disorder-specific differences between metabolite-predicted and chronological age. Mental disorders were ascertained from health records and self-reported physician diagnoses. We analysed nine diagnostic groups and 45 individual disorders and assessed sex and age group differences and associations with polygenic scores. Findings Among 225 212 participants (54% female; mean age 56.97), 38 524 had a diagnosis preceding baseline. Substance use, psychotic, affective and neurotic disorders were associated with a metabolite-predicted age older than chronological age, largest for psychosis (β=0.556, 95% CI 0.250 to 0.861, p<0.001). Obsessive-compulsive and eating disorders were associated with a metabolite-predicted age younger than chronological age. Several associations were stronger in males and in individuals aged <65 years. Higher genetic liability to depression, autism and attention-deficit/hyperactivity disorder predicted an older metabolomic age (β range=0.020 to 0.047), whereas polygenic scores for psychosis and tobacco use disorder predicted a younger metabolomic age (β range=–0.023 to –0.040). For obsessive-compulsive disorder and anorexia nervosa, clinical and genetic associations indicated younger metabolomic ageing. Conclusions Metabolomic ageing in mental disorders is heterogeneous. While many disorders are associated with an older biological age, some are linked to a younger biological age. Divergence between genetic liability and clinical phenotypes suggests that non-genetic factors shape biological ageing differences. Clinical implications Biological age should not be assumed to uniformly exceed chronological age across mental disorders. Sex and age-specific approaches could improve understanding of biological ageing processes in psychiatry.

Question To what extent are psychiatry guidelines supported by high-level evidence? Study selection and analysis Guidelines from the American Psychiatric Association, European Psychiatric Association, WHO and World Federation of Societies for Biological Psychiatry (2014–2024) were selected. Recommendations were graded by guideline authors’ levels of evidence (LOE) appraisal (standardised to the Grading of Recommendations, Assessment, Development and Evaluations framework (high, moderate, low, very low)) and by the highest-level study referenced (meta-analysis, randomised controlled trial (RCT), observational study, expert opinion, etc.). Findings 24 guidelines, containing 545 recommendations, were included. Of 82 guidelines screened, 29 (35%) had not been updated in a decade. 63 (11.6%) recommendations were rated by guideline authors as based on high LOE. The proportion was the highest for pharmacotherapies (41/281 (14.6%)) and the lowest for somatic assessment (0/13 (0%)). The proportion of high LOE recommendations varied between publishers (European Psychiatric Association: 20 %, WHO: 1.6 %). For high LOE recommendations, only those concerning pharmacotherapies cited meta-analyses based on double-blind studies using adequate controls. A large proportion (n=241 (44.2%)) of recommendations cited either a meta-analysis of RCTs (n=155 (28.4%)) or ≥two RCTs (n=86 (15.8 %)). There were few recommendations primarily addressing self-harm (n=2), autism (n=3), attention-deficit/hyperactivity disorder (n=3), prevention (n=3), patient involvement (n=3) or discontinuation (n=6). Conclusions Clinical guidelines in psychiatry frequently cite RCTs, but the evidence is often downgraded by guideline authors, highlighting the need for better quality trials. LOE varies across areas, with pharmacotherapies supported by the highest quality evidence. Organisations should commit to a timely update of guidelines covering all areas of psychiatry.

Background Loneliness is highly prevalent among Chinese older adults. Mindfulness-based interventions for older adults (MBOA) have demonstrated potential in alleviating loneliness. However, few studies have employed active controls with long-term follow-up. Objective This study aimed to assess the efficacy of MBOA in reducing loneliness compared with social contact control (SCC). Methods This parallel, randomised controlled trial (RCT) assigned community-dwelling lonely Chinese older adults (≥60 years) in Hong Kong to MBOA or SCC. Both interventions comprised 8 weekly 1.5-hour group-based face-to-face sessions. Assessments were conducted at baseline, postintervention and at 6-month and 12-month postrandomisation. The primary outcome was loneliness score at 12 months, analysed using analysis of covariance under the intention-to-treat approach. Secondary outcomes included depression, anxiety, health-related quality of life and healthcare utilisation. Changes in psychological measures were analysed using linear mixed models. Findings A total of 245 eligible participants were randomised to MBOA (n=123) or SCC (n=122). No significant between-group difference in primary outcome was found (mean difference=–0.14, p=0.52, effect size=–0.21), although both groups showed improvement in loneliness (within-group effect size: MBOA=–0.58, SCC=–0.31). MBOA participants reported reduced depressive symptoms and a decreasing trend in anxiety at 6 months compared with SCC. Conclusion This is the first RCT examining efficacy of MBOA in alleviating loneliness among Chinese older adults using an active control with long-term assessments. MBOA is not superior to SCC in reducing loneliness, although it may reduce psychological symptoms. Clinical implication Clinicians could consider prioritising mindfulness-based interventions for lonely older adults when depressive or anxiety symptoms are prominent.

Background The mechanisms linking early environmental risk (EER) and obesity via the interplay of mental health and lifestyle factors in the early life stage remain unclear. Objective To examine whether EER was associated with later mental health, lifestyle factors and obesity and to identify the mediating roles of mental health and lifestyle in these relationships. Method Using data from the Millennium Cohort Study (valid n=5401), we longitudinally assessed the relationship between EER (prenatal risks, neonatal risks, low socioeconomic status, maternal psychological problems and harsh parenting; 9 months to age 3 years), mental health problems in childhood (internalising and externalising problems; age 7 years), lifestyle factors in early adolescence (diet, exercise, smoking and drinking; age 11 years) and obesity in late adolescence (age 14–17 years). Structural equation modelling was used to test proposed pathways. Findings The proposed model showed an acceptable fit (Comparative Fit Index=0.926, Tucker-Lewis Index=0.875, root mean square error of approximation=0.034, standardised root mean square residual=0.046). EER was significantly associated with later mental health problems, lifestyle factors (ie, diet, exercise, smoking) and obesity. Higher EER was modestly associated with higher obesity risk via the interplay of externalising problems and drinking (β=0.01, p=0.036). The sex-stratified model results indicated differences between males and females. Conclusion By highlighting the importance of EER and the mediating role of lifestyle factors in mental health and later obesity risk, our findings provide evidence of shared risk mechanisms linking mental and physical health. Clinical implications These findings suggest that integrating mental health assessment (especially externalising symptoms) with routine screening for adolescent alcohol use and other risk factors could inform more targeted obesity prevention in clinical and public health settings.

Background Prevention of future deaths (PFD) reports issued by coroners in England and Wales identify systemic safety hazards but are difficult to analyse at scale. Reports are not machine-readable, lack consistent metadata and cannot be reliably searched or exported, meaning prior national reviews have relied on labour-intensive manual screening and coding. Objective To evaluate whether a fully automated, vision-enabled large language model (LLM) pipeline (PFD Toolkit) can replicate and extend the Office for National Statistics (ONS) thematic review of child-suicide PFD reports, and to assess concordance with blinded clinical adjudication. Methods All PFD reports published between July 2013 and November 2023 (n=4730) were scraped from judiciary.uk and processed using PFD Toolkit, which combines optical character recognition with LLM-powered screening and thematic coding. Reports were classified for child suicide (≤18 years), addressee categories and 23 coroner-concern subthemes mirroring the ONS coding frame. Agreement was evaluated against a blinded clinical reference standard: three psychiatrists independently adjudicated a stratified sample of 146 reports (73 Toolkit-positive cases and 73 decoys), with disagreements resolved by consensus. Inter-rater reliability and index-reference agreement were quantified using kappa statistics. Findings The Toolkit identified 73 child-suicide PFD reports between July 2013 and November 2023, compared with 37 identified in the ONS review. 62 cases fell within the ONS analytical window, and 11 pre-dated the introduction of suicide-related tags on the PFD archive. Pre-consensus inter-rater reliability among clinicians was substantial to almost perfect (Fleiss’ =0.75, 95% CI 0.65 to 0.84). Post-consensus agreement between the Toolkit and the clinical reference standard was substantial to almost perfect (Cohen’s =0.93, 95% CI 0.77 to 1.00; raw agreement 97%). End-to-end screening, coding and tabulation of all reports completed in 5 min 29 s on a consumer-grade laptop. Conclusions A national thematic review of child-suicide PFD reports can be fully automated with high concordance to expert judgement, dramatically reducing time and labour while recovering previously missed cases. Clinical implications Automated analysis of PFD reports enables rapid, reproducible surveillance of recurring system failures, supporting more timely public health intelligence, policy responses and learning from coronial data.

Background A child’s hospitalisation may have long-term influences on parental mental health, which can affect child health. Objective To describe the prevalence of and examine factors associated with parents’ depression and anxiety symptoms over time. Methods This prospective cohort study in 14 countries measured parent mental health during their child’s hospitalisation, at discharge and 3 months postdischarge (2023–2024). We included parents ≥18 years staying at a Ronald McDonald House® during their child’s hospitalisation. Exposures were parent, family and child psychosocial and health factors and hospital experiences. Outcomes were parental depression and anxiety symptoms. We used mixed-effects logistic regression. Findings 3350 parents, including 2594 (78.6%) mothers, 616 (18.1%) fathers and 131 (3.3%) other caregivers, participated during hospitalisation; 1751 (52%) at discharge, and 2395 (71%) postdischarge. Prevalence of depression and anxiety symptoms was high during hospitalisation (49.7% and 69.0%, respectively) and decreased modestly at discharge (44.6% and 59.5%, respectively), and postdischarge (42.8% and 59.2%, respectively). Over time, probabilities of depression symptoms decreased among those with high, moderate and low levels of social support (50%, 27%, 5%, respectively), and self-care (29%, 27% and 22%, respectively). Probabilities of depression symptoms decreased among those with high or moderate perceived levels of family-centred care (high: 20% decrease; moderate: 11% decrease, compared with low). In contrast, probabilities of depression symptoms increased among those with high or moderate levels of unmet basic needs (high: 18% increase; moderate: 8% increase, compared with low) and poorer ratings of their child’s health (high: 68% increase; moderate: 32% increase, compared with low (healthier)). These trends were similar for anxiety symptoms. Conclusions Prevalence of depression and anxiety symptoms is high among parents and only decreases modestly postdischarge. Clinical implications Routine screening and ongoing services may lower the risk of prolonged parental mental health symptoms, but more research is needed.

Background Although transcranial magnetic stimulation (TMS) protocols are safe and efficacious therapies for treatment-resistant depression (TRD), they remain inaccessible for many people in the UK and internationally. One of the main reasons for this is a lack of evidence demonstrating their value-for-money to commissioners. Objective To assess the cost-effectiveness of repetitive transcranial magnetic stimulation therapy (rTMS) and intermittent theta-burst stimulation (iTBS) versus treatment-as-usual (TAU) for treating TRD in UK mental health care services, and to evaluate operational circumstances underpinning cost-effectiveness. Methods This economic evaluation used data from the BRIGHTMIND trial (n=255), the SMD trial (n=187) and a study-specific structured expert elicitation exercise (n=7) to model the cost and consequences for each alternative. All findings were produced on a probabilistic basis from a Markov model using Monte Carlo simulation methods. Cost-effectiveness was assessed via incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained over an 18-month time horizon from the perspectives of the UK’s NHS and personal social services and from a broader societal perspective recognisant of informal care hours and productivity costs. Scenario analyses and an operational sensitivity analysis explored the impacts alternative methodologies, service delivery cases and perspectives had on base case findings. Findings From a health service perspective, rTMS and iTBS had pairwise ICERs of £12 093 and £12 959 per QALY compared to TAU, respectively. When incrementally compared, iTBS had an ICER of £16 621 versus rTMS. From a broader societal perspective, both rTMS and iTBS reduced informal care hours and were cost-saving compared with TAU. Study findings were particularly sensitive to service delivery, with the probability of being cost-effective ranging from 98% with high throughput and prompt delivery to approximately 4% with low throughput and prolonged delivery. Conclusions TMS therapies improve health, reduce informal care requirements, reduce health service utilisation and offset their costs when considered in terms of productivity losses to society. rTMS and iTBS are cost-effective and should be considered for wider clinical implementation provided they are delivered at sufficient scale and in a time-efficient manner. Clinical implications TMS can serve as a cost-effective alternative for treating moderate to severe depression after second-line treatment failure with non-psychological therapies.

Background Rates of intimate partner violence (IPV) and HIV in South Africa are among the highest globally. IPV is associated with a range of adverse mental health and HIV outcomes. The Common Elements Treatment Approach (CETA) is a transdiagnostic, evidence-based intervention delivered by lay providers. Objective To compare the effectiveness of CETA to active attention control in reducing IPV, depression, post-traumatic stress disorder (PTSD) and substance use among women at risk of poor HIV outcomes who have experienced IPV. Methods Women living with HIV with an unsuppressed viral load or at risk for poor adherence and experienced past 12-month IPV were recruited from Johannesburg-area clinics and randomised 1:1 to CETA or control (SMS HIV appointment reminders plus safety checks and planning). The primary trial outcome was HIV retention and viral suppression, under review elsewhere. This paper reports secondary outcomes, evaluated at 3 and 12 months: IPV, depression, PTSD and substance use. Findings Participants were enrolled between 11 November 2021 and 19 July 2023 and randomised to CETA (N=202) or control (N=197). In the intent to treat analysis, the Cohen’s d treatment effect for depression at 3 months was 0.24 (difference in mean change –3.1; 95% CI –6.1 to 0.1) and 0.48 at 12 months (–6.2; 95% CI –9.5 to –2.8). The PTSD treatment effect was 0.39 at 3 (–0.3; 95% CI –0.5 to –0.1) and 0.47 at 12 months (–0.3; 95% CI –0.5 to –0.2). Effect sizes were larger in a subgroup of participants with the top 50% of baseline symptom scores (depression: d=0.50, d=0.74; PTSD: d=0.58, d=0.94, at 3 and 12 months, respectively). There were no statistically significant differences in change for substance use or IPV. At baseline, only 12% of participants had past 3-month substance use and 32% had past 3-month or ongoing experiences of IPV, which made these outcomes challenging to evaluate. Conclusions CETA was effective for reducing depression and PTSD, including among high severity participants and at an extended follow-up. Future studies with increased power for substance use and IPV outcomes are warranted. Clinical implications CETA is a recommended treatment for depression and PTSD among this population. Trial registration number NCT04242992.

Background Sex differences in adolescent mental disorders are well documented, but less is known about how these differences evolve during the transition to adulthood, particularly during the shift from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS), a critical period marked by vulnerability to discontinuity of care. Objective To examine sex-specific differences in psychiatric symptom profiles and clinical trajectories during the CAMHS–AMHS transition using data from the European MILESTONE project, a 2-year longitudinal study. Methods A cohort of 1004 adolescents (aged 17–19) in CAMHS was assessed at baseline (T1), 9 months (T2), 15 months (T3) and 24 months (T4). Measures included the Child Behavior Checklist/Adult Behavior Checklist, Health of the Nation Outcome Scales for Children and Adolescents, and the Specific Level of Functioning Scale. Multilevel modelling included sex, diagnosis and time point as covariates, testing three-way interactions for differential trajectories. Findings Males showed higher symptom severity and impairment across measures, particularly in anxiety/somatic/trauma, eating disorder/obsessive-compulsive disorder (ED/OCD) and schizophrenia. Females exhibited better functioning. Significant sex differences emerged in internalising symptoms (eg, anxiety/somatic/trauma, autism spectrum disorder (ASD)), externalising symptoms (eg, attention deficit hyperactivity disorder (ADHD)), overall psychopathology (eg, ADHD, personality disorder/conduct disorder/substance use disorder) and functioning (eg, ED/OCD, schizophrenia spectrum disorder). Conclusions Sex-related differences in symptom severity, diagnosis and functioning persist across the CAMHS–AMHS transition, with males generally more impaired and females showing better adaptive outcomes. Clinical implications Identifying sex-specific trajectories can enhance personalised transitional care, reduce misdiagnosis and guide targeted interventions—especially for under-recognised presentations such as ADHD/ASD in females and ED in males. Trial registration number ISRCTN83240263.

Background Medication safety studies in pregnancy typically focus on selected or composite outcomes (eg, any malformation) to test specific hypotheses or verify suspected safety signals, potentially overlooking or masking other clinically significant associations (eg, individual malformations or malformation types). Objective To conduct a comprehensive, systematic screening for potential teratogenic safety alerts associated with first-trimester exposure to individual antipsychotics, using a tree-based scan statistic (TBSS) approach for simultaneous evaluation of a broad range of specific malformations and malformation groupings. Methods Using a US-nationwide cohort of >4.2 million mother–child dyads (2000–2020), pregnancies with ≥1 first-trimester antipsychotic dispensing were compared with antipsychotic-unexposed pregnancies. Individual congenital malformations were identified via International Classification of Diseases codes, grouped into increasingly aggregated higher-level clinically related categories. Leveraging this hierarchical classification tree, TBSS was used to scan for associations with individual malformation codes and code categories while tightly controlling type 1 error. Confounding was adjusted for via propensity score fine-stratification, and relative risks (RRs) were estimated using an unconditional Poisson scan statistic. The p-values were used to prioritise alerts for further investigation, and follow-up analyses were conducted to refine the understanding of statistical alerts. Findings Exposed pregnancies ranged from 68 (fluphenazine) to 18 366 (prochlorperazine). Antipsychotic-exposed versus antipsychotic-unexposed women tended to be older and to have a higher comorbidity burden and more healthcare encounters. Alerts for an increased risk (with p<0.1) were observed for skin anomaly after haloperidol (RR=1.88) and polydactyly after ziprasidone (RR=3.06) exposure. Results were consistent in sensitivity analyses. The data in the two external data sources were too sparse to confirm a safety alert. Conclusions TBSS identified two potential alerts previously unreported for prenatal antipsychotic exposure. Importantly, no alerts for severe or life-threatening malformations were detected. Findings from this screening-based approach, therefore, align with existing evidence suggesting that antipsychotics are unlikely to be major teratogens. Clinical implications The potential risk increase observed for some less-severe malformations and some antipsychotics needs to be weighed against the high potential for relapse and mental health deterioration following treatment discontinuation. While no consistent patterns suggesting a strong teratogenic effect have emerged thus far for newer antipsychotics, continued monitoring of these medications is important.

Background Mental health conditions are a major global challenge with rising demand for accessible, effective, scalable treatments. Digital peer support interventions are a promising way to extend support beyond clinical settings, but their effectiveness requires comprehensive evaluation. Objective To evaluate the effectiveness of digital peer support interventions in improving clinical symptoms, functioning, and treatment engagement among individuals with mental health conditions in outpatient settings. Study selection and analysis We conducted a systematic review and random-effects meta-analysis of controlled interventional studies. Five databases (MEDLINE, CENTRAL, Embase, PsycINFO) were searched up to January 2025. Studies evaluated digital peer support via online platforms, mobile apps or digital communities for people aged ≥16 years with mental health conditions. Outcomes included clinical symptoms (depression, anxiety), functioning (quality of life, social functioning) and treatment engagement. Risk of bias was assessed using Cochrane Risk of Bias 2.0 for randomised controlled trials and ROBINS-I for non-randomised studies. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Findings 29 studies including 5825 participants were included. Digital peer support was associated with small-to-moderate improvements in symptoms of depression (standardised mean difference (SMD) –0.28; 95% CI –0.42 to –0.14) and anxiety (SMD –0.47; 95% CI –0.68 to –0.27). Functional outcomes improved modestly: social functioning (SMD 0.18; 95% CI 0.07 to 0.29), quality of life (SMD 0.14; 95% CI 0.02 to 0.26), patient activation (SMD 0.39; 95% CI 0.23 to 0.55) and personal recovery (SMD 0.23; 95% CI 0.11 to 0.35). No significant effects were observed for treatment engagement or satisfaction. Preliminary evidence suggested sustained benefits for depression, anxiety and social functioning. Conclusions and clinical implications Digital peer support offers modest improvements in symptoms and functioning for individuals with mental health conditions and may be considered as an adjunct to usual care to enhance engagement and provide accessible support between clinical contacts. Key priorities include establishing optimal intervention models, clarifying longer-term benefits, and ensuring these approaches can be delivered safely and sustainably within routine outpatient services. PROSPERO registration number CRD42023445194.

Objective Suicide is a leading cause of maternal mortality, with many cases considered preventable. The Edinburgh Postnatal Depression Scale (EPDS) item 10 screens for self-harm thoughts in the past 7 days. This study aimed to investigate whether a positive response (‘hardly ever’, ‘sometimes’ or ‘quite often’) is associated with subsequent hospital-registered intentional self-harm, non-suicidal or suicidal, among postpartum women. Methods We conducted a population-based cohort study of 170 218 childbirths (38% of the source population) from 142 795 unique women in Denmark by linking nationwide registers with the HOPE cohort. Self-harm thoughts were defined as any non-zero response to EPDS item 10. The primary outcome was a hospital-recorded episode of intentional self-harm within 365 days after childbirth. To account for confounding, we applied inverse propensity-score weighting, and we used Firth’s penalised logistic regression to estimate ORs. Results Of the 170 218 childbirths, 2935 (1.7%) reported self-harm thoughts. During a mean (SD) follow-up of 303.0 (11.2) days, eight women (0.27%) with self-harm thoughts were hospitalised due to intentional self-harm, demonstrating a 24-fold higher crude rate compared with women without self-harm thoughts (0.01%). After applying weighting, the adjusted OR remained significantly elevated at 10.91 (95% CI 7.03 to 17.99). Conclusion This is the largest study to date on this topic. We found that postpartum women reporting self-harm thoughts had a low absolute risk of intentional self-harm, but the relative risk was 11-fold higher. These results highlight the importance of further assessment and timely support for mothers identified as being at risk.

Background Antidepressants are among the most prescribed medications in the USA, yet challenges in access to mental health treatment persist. Objective To assess current and lifetime antidepressant and psychotherapy use among American adults, and examine attitudes towards potential federal restrictions on antidepressant prescribing. Methods We conducted a cross-sectional survey study using data from a national non-probability internet-based panel weighted to approximate national demographics (age, gender, race and ethnicity, education, US census region, and urbanicity) based on 2020 US Census data. Data were collected between 10 April and 27 May 2025 from 30 810 adults residing in the USA. The primary outcomes were self-reported current and past antidepressant and psychotherapy use, and support for or opposition to potential federal restrictions on antidepressant prescribing. Logistic regression models estimated demographic and treatment-related features associated with these outcomes. Findings Among 30 115 respondents with complete antidepressant data, 16.6% reported current antidepressant use, and of 30 098 respondents with psychotherapy data, 10.4% reported current psychotherapy. Use of both treatments was significantly greater among White respondents compared with all other racial groups. When asked about potential federal restrictions on doctors prescribing antidepressants, 16.4% of respondents supported and 48.0% opposed such regulation, with lesser opposition among those of male gender (OR 0.69, 95% CI 0.65 to 0.73), and greater opposition among those with lifetime antidepressant treatment (OR 2.37, 95% CI 2.21 to 2.54). Conclusions Antidepressant and psychotherapy use remains unevenly distributed across demographic groups. A significant proportion of adults in every US state oppose efforts to restrict access to antidepressant prescribing, reflecting broad public support for maintaining access to treatment. Clinical implications Findings from this study suggest that restrictive policies on antidepressant prescribing are unlikely to align with public sentiment and may risk exacerbating existing inequities in care.

Background The cognitive effects of cannabis use in older adults remain unclear, despite increasing use for medical and recreational purposes in this age group. Objective To investigate associations between cannabis use, cognitive performance and dementia risk in older individuals, using large population cohorts and Mendelian randomisation (MR) to explore potential causal relationships. Methods Observational analyses were conducted using the UK Biobank (UKB) and the US Million Veteran Program (MVP). In UKB, cross-sectional and longitudinal cognitive performance across five domains was compared between lifetime cannabis users (up to 18 975 participants) and non-users (up to 60 598 participants). In MVP, cannabis use disorder (CanUD; n=12 222) was examined in relation to incident all-cause dementia using Cox proportional hazards models. MR analyses assessed potential bidirectional causal relationships between cannabis use, cognitive function and dementia. Findings At baseline, cannabis users performed modestly better on tests of numeric memory (beta=0.07, 95% CI 0.06 to 0.09, p<0.001) and fluid intelligence (beta=0.12, 95% CI 0.10 to 0.13, p<0.001), but no significant differences were observed in longitudinal cognitive change. In MVP, CanUD was not significantly associated with dementia risk (HR=1.11, 95% CI 0.97 to 1.26, p=0.12). MR analyses provided no evidence of a causal relationship between cannabis use and either cognitive performance or dementia risk. Conclusions Cannabis use was not linked to longitudinal cognitive decline or dementia risk. Within the limits of these cohorts, we found no evidence that cannabis use contributes substantially to cognitive ageing or dementia risk in older adults. Further research with detailed exposure assessment and longer follow-up is warranted to confirm these findings. Clinical implications Cannabis use in older adults does not appear linked to faster cognitive decline or higher dementia risk. Occasional or prior use may not substantially affect cognitive ageing, though safety at higher doses or prolonged use remains uncertain. Clinicians should inquire about cannabis history and consider cognitive screening in routine care.

Background Depression is a leading cause of global disability, and subthreshold cases contribute substantially to the burden. Cognitive behavioural therapy (CBT) is effective for depressive symptoms, but its impact on social functioning in subthreshold depression remains unclear. Objective This study evaluated the effects of smartphone-based CBT on social functioning and personal health records among individuals with subthreshold depression and examined whether a personalised and optimised therapy (POT) algorithm enhanced these outcomes. Methods We performed a secondary analysis of the RESiLIENT trial (n=5361). Participants were stratified by baseline Patient Health Questionnaire-9 (PHQ-9) scores (0–4 and 5–14) and randomised to nine CBT app groups or a self-check group. Outcomes included social functioning and health records. A mixed-effects model for repeated measures was used to analyse the outcomes. The POT algorithm selected CBT skills tailored to individual characteristics. Findings Depressive symptoms improved in both PHQ-9 groups compared with those of the self-check group, but gains in social functioning were modest, observed mainly in the PHQ-9 score ≤4 group. No consistent benefits were seen for health behaviours, job resignation, sick leave or healthcare costs. However, in a simulated randomised comparison using 10-fold cross-validated datasets, the POT algorithm had potentially beneficial effects for productivity (standardised mean difference (SMD)=0.16, 95% CI 0.03 to 0.29) and social adjustment (SMD=–0.13, 95% CI –0.26 to 0.00). Conclusions Smartphone CBT effectively reduced depressive symptoms but showed limited impact on social functioning and healthcare costs. Personalised optimisation may modestly improve productivity and adjustment, suggesting its promise for enhancing social outcomes. Clinical implications Personalised tailoring of CBT skills may strengthen the effects of digital interventions on social functioning. Trial registration number UMIN000047124.

Question Psychological distress is increasingly prevalent among university students, raising concerns about their mental health. This review aimed to assess the strength and credibility of evidence on the efficacy of psychosocial interventions for improving mental health in this population. Study selection and analysis We conducted an umbrella review of systematic reviews (SRs) with meta-analyses of randomised controlled trials assessing psychosocial interventions among university students. Searches were performed in Medline, PubMed, Cochrane Central, PsycINFO, CINAHL, Epistemonikos and Campbell Collaboration from 1 January 2014 to 1 February 2026. Data on intervention type, comparator, outcome and study-level effect sizes were analysed using inverse-variance random-effects models with restricted maximum likelihood estimation of between-study heterogeneity (²). Strength of associations was evaluated according to umbrella review criteria, reporting quality using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Findings A total of 34 SRs were identified. After excluding overlapping syntheses, 28 unique meta-analyses from 12 SRs were included. Mindfulness-based interventions versus inactive controls for distress (standardised mean difference (SMD) –0.40; 95% CI –0.53 to –0.28) showed highly suggestive evidence (class II; GRADE: low; AMSTAR: high). Seven associations provided suggestive evidence (Class III): mindfulness-based interventions versus inactive controls for anxiety (SMD –0.54; 95% CI –0.81 to –0.27) and depression (SMD –0.52; 95% CI –0.65 to –0.39); cognitive-based interventions versus inactive controls for anxiety (SMD –0.48; 95% CI –0.62 to –0.34) and depression (SMD –0.60; 95% CI –0.75 to –0.45); cognitive-based interventions versus active controls for well-being (SMD –0.30; 95% CI –0.42 to –0.18); positive psychology interventions versus inactive controls for distress (SMD –0.22; 95% CI –0.35 to –0.10); and multimodal interventions versus inactive controls for distress (SMD –0.85; 95% CI –1.32 to –0.87). The remaining associations were weak or non-significant, generally supported by low or very low certainty and mostly low or very low reporting quality. Conclusions The most robust evidence emerged for mindfulness and cognitive-based interventions, with some support also for positive psychology approaches. These interventions appear to improve depression, anxiety, distress and well-being among university students, though further rigorous research is needed. PROSPERO registration number CRD42023493618.

Background Risk prediction tools may help identify youth who are at risk of developing depression or anxiety and allow personalised preventive interventions to be delivered. However, with concerns for implementation, it is important to directly engage with youth to understand their attitudes. Objective To qualitatively explore UK-based youth attitudes towards risk prediction tools and personalised preventive interventions for depression and anxiety. Methods Online semistructured interviews were conducted with a convenience sample of youth aged 16–25 years (n=25) and analysed using reflexive thematic analysis. Findings Analysis generated four themes: (1) Helpful or harmful: risk prediction as a ‘double-ended sword’ explores the potential benefits and consequences of risk scores; (2) ‘Taken with a grain of salt’: are risk prediction models the way forward? focuses on participants’ scepticism towards risk prediction tools, including ethics and privacy; (3) ‘It really depends on the person’: respecting the individual in prevention emphasises the importance of personal choice and individual differences and (4) ‘You still need like a person in the process’: the importance of human involvement encapsulates participants’ belief regarding human involvement in development and implementation. Conclusions While youth appear open to risk prediction tools and personalised preventive interventions, they highlighted concerns that must be addressed before implementation, including ethics, accuracy, privacy and feasibility. Clinical implications Going forward, researchers should prioritise stakeholder involvement, using active collaboration to identify ways in which these concerns can be addressed, which may increase acceptability and uptake. Human contact, alongside agency and choice, are further factors to consider.

Background Cognitive impairments are common in depression and often persist beyond mood resolution. However, the relationship between cognitive performance, its neurological underpinnings, and future depression risk is unclear, limiting strategies for primary and secondary prevention. Objective Our objective was to determine whether cognition associates with subsequent depression, both relapse and first-episode occurrences. Methods 1862 UK Biobank participants with a history of International Classification of Diseases (ICD)-10-defined depression in remission (RD) (mean (SD) age: 52.7 (7.13) years) were age-matched and sex-matched to 1862 participants without depression history or current antidepressant use. Cognitive scores were compared between groups at the composite (z-score), domain and task levels. MRI-derived phenotypes assessed brain network structure and functional connectivity. Longitudinal associations with future depression were assessed using logistic regression models and a Cox proportional hazards model controlling for key confounders. Findings Participants with RD had a higher risk of future depression (33%) than controls (13%), including when we accounted for temporal differences in longitudinal assessment (HR=3.16 (95% CI 2.71 to 3.67), global proportional hazard assumption p=0.07). Composite cognitive performance in controls was inversely associated with future depression risk (risk estimated marginal means: 0.25% at –1SD, 0.20% at mean, 0.15% at +1 SD). In RD, this relationship was reversed (0.74% at –1SD, 0.90% at mean, 1.10% at +1 SD). Executive functioning, processing speed and reasoning task scores all contributed. Higher grey matter in default mode network regions was associated with better concurrent cognitive performance across all participants, but not with future depression risk. Other MRI findings were limited. Conclusions RD carried a threefold higher risk of future depression than controls. Cognitive performance was a risk marker for future depression in both groups but in opposing directions. Neuroimaging metrics provided little predictive value. Clinical implications Personalised risk factor assessment for depression is likely to be dependent on depression history. Those without previous history of diagnosed depression are at higher risk of future depression when cognitive performance is lower at baseline. RD is a high-risk group for future depression, and those with relatively higher cognitive performance may be more likely to report future depressive symptoms.

Are we properly assessing the acceptability of mental health interventions from a service user’s point of view? A treatment can be efficacious and effective but still not acceptable to a service user. For example, someone with psychosis may find a treatment that improves symptoms but causes significant weight gain and sedation unacceptable. Despite significant progress being made in developing safe and effective interventions for mental health problems, a notable proportion of people remain in need. The reasons for this are complex. Part of the problem could be an inadequate focus on how ‘acceptable’ interventions really are to service users given their views and specific circumstances. Treatment acceptability has been a rather poorly defined concept. This has led to researchers using several methods to assess their own ideas about what service user acceptability is. This can include methods such as using recruitment and withdrawal data. But such data may not be true markers of acceptability to a service user. Current approaches to assessing acceptability need improvement. Existing acceptability questionnaire measures are not widely used and are often developed for specialist settings. Crucially, very few have had any stated involvement of people with mental health conditions in their development. This approach risks not listening to service users’ voices fully. Developing better ways of understanding and assessing service users’ views of treatment acceptability in mental health could have many benefits—including empowering individual service users to identify interventions that they can and cannot accept. It is time to better understand what ‘acceptable’ really means in mental health.

Background Suicide is a major public health concern, particularly among Veterans. The U.S. Department of Veterans Affairs Veterans Health Administration (VHA) employs the Recovery Engagement and Coordination for Health–Veterans Enhanced Treatment (REACH VET) model to prioritise high-risk patients for targeted clinical attention. Objective REACH VET 1.0 (RV 1.0) was developed on 2008–2011 data. To reflect changes in clinical practice and populations, VHA updated it to REACH VET 2.0 (RV 2.0). This study describes its development and validation. Methods RV 2.0 used longitudinal data from 7,248,170 VHA patients (4,967 suicide deaths) in 2018–2019, with 650 time-varying demographic, clinical and area-level predictors derived from a 2-year lookback (2016–2019). An ensemble of Elastic-Net logistic regression models was trained on 2018 data and evaluated monthly at the population level in 2019, focusing on the top 0.1% intervention risk tier. Analyses assessed model discrimination, suicide detection, risk concentration, subgroup consistency (sex, age and race/ethnicity) and performance relative to RV 1.0 using the same percentile-based risk strata. Results RV 2.0 outperformed RV 1.0 across all risk strata, with better discrimination (C-statistic 0.76 vs 0.69) and consistent performance across demographic subgroups. Within the top 0.1% of predicted risk, RV 2.0 identified more deaths, higher suicide rates and greater mortality risk concentration both when averaged across the 12 monthly 2019 test sets (5.6 vs 3.6; 83.6 vs 53.7 per 100,000 person-years; 21.0 vs 14.1) and when annualised for 2019 (67 vs 43; 2.7% vs 1.7%; 1,003 vs 644 per 100,000 person-years; 26.7 vs 17.1). Conclusions RV 2.0 improves suicide risk stratification among Veterans, demonstrating better performance and consistent prediction across subgroups and highlighting the need for regular model updates and evaluation. Clinical implications RV 2.0 enables targeted interventions and, since its national VHA implementation in June 2025, continues to support system-wide suicide prevention.

Climate change has an increasing physical and mental health toll on young people globally. In this Perspective, we suggest that the extent of mental health impacts is likely to be underestimated in the low- and middle-income countries which are most vulnerable to the effects of climate change. We highlight a strong global inverse relationship between internet connectivity and climate vulnerability, which poses significant challenges for understanding climate change’s worldwide mental health impacts and for developing effective mitigation strategies. Inclusive methodologies that enable engagement with offline but climate-vulnerable communities are therefore needed. Such locally grounded mental health research is essential to ensure that climate policies are informed by the lived experiences of populations on the frontlines of the crisis, many of whom remain digitally disconnected and excluded from much current research.

Mental health clinical trials in the UK face significant recruitment barriers, with mental health studies comprising just 3.3% of approved interventional medicinal product trials. Challenges include the limited numbers of trials and clinician gatekeeping—where clinicians decide whether or not to inform patients about research opportunities, limiting patient awareness and recruitment. The ‘Count Me In’ (CMI) approach, an opt-out recruitment model launched in Oxford in 2021 and then in Liverpool City Region in 2024, aimed to address these issues by directly contacting patients to discuss research opportunities, empower them in the shared decision process and embed participation in research into real-world clinical care. In this paper, we discuss the need for advancing beyond the original CMI model, including the requirement for enhanced data capture, mechanism for patient outreach that prioritises inclusive practices for improving participation and ensuring diverse, representative trial populations.

Microaggressions constitute a pervasive and insidious form of discrimination, frequently manifesting as subtle, unconscious and unintentional actions that disproportionately affect individuals based on gender, race, ethnicity, religion, age, sexual orientation, culture or disability. Although such phenomena are observed across a wide range of contexts, the present perspective article focuses specifically on women working as providers of healthcare services in psychiatry. For these professionals, microaggressions commonly take the form of implicit biases, dismissive attitudes and unequal treatment, all of which contribute to a professional environment in which their contributions are systematically undervalued. These behaviours are reinforced by cultural norms and entrenched systemic practices, which serve to normalise discrimination, impede career progression and contribute to psychological distress. Addressing such stereotypes and discriminatory practices at both micro and macro levels is therefore essential. This article draws on both the existing literature and collective personal experiences, arguing that the complexity of microaggressions in psychiatry necessitates a multidimensional analytical approach. By incorporating the perspectives of 21 women psychiatrists and psychologists from 15 countries across six continents, this perspective identifies recurring challenges related to service delivery and career progression. Cross-regional analysis reveals persistent patterns, including commentary on physical appearance, dismissal of professional contributions, violations of personal boundaries and forms of structural marginalisation. These findings extend the academic understanding of microaggressions in psychiatry and underscore the need for systemic reform and cultural transformation.

Background Deliberate self-harm (DSH) is a major public health concern among patients with schizophrenia spectrum disorders (SSDs). Although forensic patients with SSD show high rates of DSH, they remain under-represented in suicidology research, and differences in risk profiles compared with non-forensic patients are poorly understood. Objective To compare sociodemographic, clinical, neuropsychological and criminological correlates of lifetime DSH between forensic and non-forensic patients with SSD and identify subgroup-specific vulnerability markers. Methods Data were drawn from the multinational EU-VIORMED study across five European countries. Participants (N=392) aged 18–65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnosis of SSDs completed standardised assessments. Lifetime DSH was measured dichotomously. Separate LASSO logistic regression models identified the strongest correlates of DSH in forensic and non-forensic subsamples. Findings Lifetime DSH prevalence was high in both groups (45.9% forensic; 39.5% non-forensic). In forensic patients, the strongest correlate was comorbid personality disorder (β=0.78), followed by functional impairment (β=0.02–0.26). In non-forensic patients, interpersonal victimisation (β=0.85) was the strongest correlate, followed by personality disorder (β=0.71), male gender (β=0.69), lifetime substance use (β=0.37) and psychopathological indicators (PANSS (Positive and Negative Syndrome Scale) items; β=–0.10–0.32). Overall, DSH in forensic patients was more strongly associated with personality pathology and functioning, whereas in non-forensic patients it was linked to trauma, clinical severity and sociodemographic factors. Conclusions Despite similar DSH prevalence, forensic and non-forensic SSD patients showed distinct patterns of associated factors, suggesting different mechanisms of risk. Clinical implications Suicide prevention in SSD should adopt tailored risk formulations, emphasising personality pathology and functioning in forensic settings and trauma-informed, integrated care in non-forensic services.

Background More effective and better tolerated treatments are urgently needed for people with mental health disorders, such as anxiety, depression and psychosis. However, the rate of translation of positive results from early phase studies into clinically validated treatments remains painstakingly slow. The scientific literature on mental health preclinical and early interventions is burgeoning at pace, making it difficult for researchers, practitioners and policymakers to identify and track new developments. Objective As part of the Wellcome-funded Global Alliance of Living Evidence for aNxiety, depressiOn and pSychosis project, we aimed to develop and evaluate an automated approach to track the evolution of mental health research over time, detect emerging trends and suggest open questions. Methods Our approach used topic modelling, large language models and time-series forecasting in combination. We applied our approach to a corpus of 182 747 titles and abstracts extracted from the OpenAlex database for 2015–2025. Using topic modelling to identify topics and then tracking topic mentions over time, we built a time series predictive model and predicted ‘trendiness’ based on sustained increased mentions above baseline expected from model predictions. We evaluated our approach retrospectively using a blinded expert study of a randomly selected sample of trending and not trending topics. Finally, we developed a novel topic-augmented generation approach to suggest open questions in trendy topics and evaluated the approach by comparison to baseline-generated questions without topic augmentation. Findings Our approach detected 973 topics and predicted 165 (17%) of those as trending. Key topics that the model predicted as trending included ‘ketamine for treatment-resistant depression’, ‘student mental health in academia’ and ‘COVID-19 psychosis’. We found that domain experts largely agreed with the model’s predictions of trendiness. Topic-augmented generated questions were more specific than baseline generated questions. Conclusions Our approach enables identification of new developments and open questions. Future work will improve temporal pattern tracking and use full texts. Clinical implications Our approach can support all stakeholders to gain an overview of the published literature, assess temporal patterns, identify trends and rank open questions.

Background Tackling the global burden of mental health conditions and substance misuse is an international priority. In recent years, strategic work has begun to develop mental health services in Ethiopia and strengthen human rights protection for people with mental health conditions. To inform mental health service planning in the Somali region of Ethiopia, the extent of mental health conditions and substance misuse requires quantification. Objective We aimed to investigate associations between problematic khat use and mental health conditions in Ethiopia’s Somali Regional State (SRS). Method We carried out a quantitative household survey of 844 randomly selected residences in two cities in Ethiopia’s SRS: the regional capital, Jigjiga (55.1%, n=465), and third largest city, Kabridahar (44.9%, n=379). We used the culturally validated Problematic Khat Use Screening Test and Mini International Neuropsychiatric Inventory to assess the prevalence and factors associated with mental health conditions and problematic khat use. Findings Out of 844 participants, 18.6% (n=156) met criteria for major depression, 11.1% (n=92) met criteria for post-traumatic stress disorder (PTSD) and 5.7% (n=48) expressed suicidal ideation. The combined prevalence of these mental health conditions was 21.8% (n=186). Men reported more aggregated mental health conditions than women (30.6%, n=97 vs 16.9%, n=89). Adjusted regression analyses showed that people with problematic khat use had more than twice the prevalence of major depression (prevalence ratio (PR) 2.5, 95% CI 1.7 to 3.5), recurrent depression (PR 2.8, CI 1.8 to 4.4), suicidal ideation (PR 2.4 CI 1.9 to 5.3), PTSD (PR 3.1, CI 1.9 to 5.3) and any mental health condition (PR 2.4, CI 1.7 to 3.4) compared with people without problematic khat use. Conclusion This study provides the first data regarding population mental health needs and harms associated with problematic khat use in the SRS, to inform the design, development and prioritisation of mental health services and substance regulation and policy. Clinical implications Associations between problematic khat use and a range of poor mental health outcomes demonstrate the importance of targeted services for this population. Further research is needed to explore causal pathways underlying these associations.

Background The 11th revision of the International Classification of Diseases (ICD-11) introduced revised diagnostic criteria for a depressive episode (DE) and generalised anxiety disorder (GAD). The International Depression Questionnaire (IDQ) and the International Anxiety Questionnaire (IAQ) are the first self-report measures developed to assess and screen these disorders according to the ICD-11 diagnostic rules. Objective This study aims to validate the IDQ and the IAQ in clinical and community samples, examining internal consistency, factorial validity and construct validity. Methods The cross-sectional, observational multicentre validation study applied internal consistency testing, confirmatory factor analyses and item response theory (IRT) in a clinical sample (n=569; age 18–73; 417 females, 118 males, 34 diverse) and a sample representative of the German general population (n=1001) by age, education and gender (500 females, 499 males, 2 diverse). Factorial and IRT model fit of the IDQ and IAQ as well as concordance with the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder-7 (GAD-7) was tested. Results Both questionnaires showed excellent internal consistency (=0.96 each) and strong factor loadings. A three-factor IDQ model and a one-factor IAQ model provided the best fit. In the clinical sample, 39.7% met ICD-11 DE criteria and 51.0% GAD criteria (overlap 32.2%). In the general population, prevalence was 5.9% for DE and 9.3% for GAD. Concordance with PHQ-9 and GAD-7 was partial, suggesting differences between ICD-11-based and established screening tools. Conclusions The IDQ and IAQ are psychometrically robust self-report measures for ICD-11 DE and GAD. They are reliable, valid, brief, easy to administer, cost-free and suitable for use in primary care and research across diverse clinical and research settings. Their availability supports standardised screening of depression and GAD in both clinical and community settings.

Background Evidence suggests that transcranial direct current stimulation (tDCS) combined with repetitive transcranial magnetic stimulation (rTMS) is more effective than either modality alone. However, the underlying neural mechanisms remain unclear. Objective To explore the effects of combined tDCS-rTMS on cortical functional networks and neural regulation processes in chronic insomnia. Methods In this randomised, double-blind, sham-controlled trial, 111 adults with chronic insomnia were allocated to real tDCS+real rTMS or sham tDCS+real rTMS. Participants received 20 weekday sessions over 4 weeks. Of these, 106 completed treatment and 103 provided functional near-infrared spectroscopy (fNIRS) data meeting predefined quality criteria. fNIRS measured oxygenated haemoglobin (Oxy-Hb) responses in prefrontal and temporal regions during a verbal fluency task (VFT) before and after treatment. The primary outcome was haemodynamic activation; secondary outcomes were functional connectivity and sleep quality. Findings Sleep quality improved in both groups, with significantly greater reduction in Pittsburgh Sleep Quality Index (PSQI) scores in the real tDCS+real rTMS group (p<0.05). No between-group differences were observed in VFT performance. However, the combined stimulation group showed significantly increased Oxy-Hb responses across multiple fronto-temporal channels, particularly in bilateral temporal regions, and greater enhancement in mean functional connectivity (p<0.05). Both interventions were well tolerated, with no serious adverse events. Conclusions This study provides neuroimaging evidence that combined tDCS and rTMS may improve chronic insomnia by enhancing activation of fronto-temporal cortices and strengthening inter-regional functional connectivity. These findings offer objective support for the clinical efficacy of the combined stimulation protocol, link neurophysiological changes to treatment optimisation and suggest potential advantages of this approach for neuromodulation-based therapeutic strategies. Clinical implications These findings suggest that tDCS combined with rTMS may represent a feasible and well tolerated non-pharmacological strategy for chronic insomnia, with potential advantages over rTMS alone at both clinical and neurophysiological levels. Trial registration number This study was registered as a clinical trial with the China Clinical Trial Registration Centre (ChiCTR2100052681).

The National Institute for Health and Care Excellence (NICE) guideline for self-harm advises against the use of risk assessment tools to predict future occurrence of repeat self-harm or suicide in individuals who have self-harmed, or to inform decisions regarding their treatment and discharge. In this perspective article, we discuss shortcomings in the process of developing this guideline, including: (1) limitations in the NICE evidence review underpinning these recommendations, which resulted in very minimal evidence being included; (2) developing definitive recommendations and drawing strong conclusions regarding the limited predictive ability and potential harms of tools, which were almost entirely based on the committee’s expertise and experience and (3) not acknowledging the uncertainty and gaps in the evidence base, particularly around model impact, acceptability and feasibility. We highlight new evidence since this 2022 guideline, including examples of international work assessing model implementation and cost-effectiveness. We propose that there is an urgent need for more rigorous primary research assessing model impact, feasibility and acceptability, as well as empirical work addressing concerns about potential harms and misuse of tools, notably the denial of care. While prediction models should not be prematurely implemented in clinical practice without adequate validation and impact assessment, well-developed and validated tools in this area have the potential to improve clinical care for individuals who self-harm. Future updates to the guideline should be informed by emerging higher quality evidence in the field.

Background Major psychiatric disorders are associated with increased risk of dementia but establishing whether psychiatric disorders causally increase dementia risk is challenging because dementia pathology can precede clinical diagnosis by decades. Prodromal psychiatric symptoms may arise long before cognitive decline, leaving open the possibility of reverse causation. Objective We aimed to determine whether non-affective psychosis or depression credibly causally influence dementia risk using a design robust to reverse causation. We tested whether people with psychiatric disorders who later develop dementia show reduced genetic liability to Alzheimer’s disease (AD) compared with dementia cases without such history. Methods We compared AD genetic liability, measured by polygenic risk scores (PRS) among dementia cases (N=7936) with and without prior non-affective psychosis (N=56) or depression (N=937) in the UK Biobank. We examined whether schizophrenia or major depressive disorder (MDD) PRS correlates with dementia liability to assess whether shared trait liability contributes to the association. Findings Dementia cases with prior non-affective psychosis or depression had lower AD genetic liability than those without a psychiatric history (psychosis: B=–0.29, 95% CI (–0.54 to –0.05), p=0.036; depression: B=–0.12, 95% CI (–0.18 to –0.05), p=0.0004), which is inconsistent with the hypothesis that the association between psychiatric disorders in dementia is explained by prodromal dementia effects. After excluding people with psychiatric diagnoses, neither schizophrenia nor MDD liability showed the negative correlations with AD liability in people with dementia expected if trait liability to those disorders per se contributed to dementia risk. Our findings instead are consistent with exposure to the disorders themselves as being associated with dementia. Conclusions Our findings are consistent with the hypothesis that psychiatric disorders are associated with increased vulnerability to dementia. Clinical implications Identification of potentially modifiable mechanisms for the association and optimal management of non-affective psychosis and depression may help reduce long-term dementia risk and inform prevention strategies.

The accelerating climate crisis is reshaping not only the physical world but also the psychological landscapes in which individuals and communities attempt to live, learn and adapt.1 2 However, a paucity of psychiatric studies on mental disorders associated with climate change is evident, highlighting a need for climate–mental health research and policy that is contextually grounded, culturally inclusive and scientifically robust.3 4 The collection of articles featured in this special collection illuminates this rapidly evolving terrain from multiple vantage points—educational, cultural, clinical, methodological and epidemiological—revealing a shared urgency. Across school systems in the Global North, climate change education remains an underdeveloped domain despite young people expressing high levels of concern about the future. Mottishaw and MacQuarrie remind us that preparing youth for a destabilised climate requires more than scientific literacy: it demands recognising and constructively engaging with the complex emotional responses...

Background Preliminary evidence indicates that social prescribing (SP) can improve children and young people’s (CYP) well-being but is limited by small non-representative samples and often relies on descriptive statistics. Given the wide implementation of SP in the UK, administrative records provide a unique opportunity to understand current practice and assess impacts on well-being. Objectives (1) To understand the quality of data captured in SP administrative records. (2) To explore which CYP are currently receiving SP and what SP entails in practice. (3) To assess the impact of SP on well-being. Methods We used administrative records from one CYP SP service in England. Records were extracted from Joy, an online platform for managing SP. Over 18 months, 770 age-eligible CYP were referred to SP, 203 of whom were successfully discharged and completed two pre-post measures of well-being (the short Warwick-Edinburgh Mental Wellbeing Scale; SWEMWBS) at least 7 days apart. We used descriptive statistics, a paired t-test to assess changes in well-being and linear regressions with interactions to test effect modification. Findings Missing data was the largest issue, with ethnicity missing for 94% of CYP. A lack of detail and inconsistent recording for both individual characteristics and SP practices also presented challenges. Despite this, we identified that most CYP were referred by their GP, followed by their school, with 97% referred because of their mental health. The most common pathway was to receive SP for around 90 days, with 10–15 link worker contacts and 6 contact hours. Following SP, SWEMWBS scores improved by 3.72 points (t(202)=17.50, 95% CI 3.30 to 4.14, p<0.001), a 20% relative increase. Exploratory analyses suggested that this increase was greater for those with lower baseline well-being. Conclusions Despite numerous challenges with missing data and data quality, we found that CYP well-being increases following SP (as it is currently implemented). The moderate effect size was consistent with larger studies of adults. Clinical implications Further development of online platforms is needed to monitor access to, nature of and efficacy of SP. For those working in SP, we recommend more training, implementation of standardised guidelines and designated time to update records.

Background Diagnosing autism spectrum disorder (ASD) in adulthood is time-consuming and markedly complicated by the requirement to distinguish between ASD and differential diagnoses also associated with social interaction difficulties, such as borderline personality disorder (BPD)—a distinction for which currently no valid screening or diagnostic tool exists. While technology-assisted diagnostics (TAD) has emerged, existing algorithms have focused on classifying between ASD and no diagnosis, not fully addressing clinical reality. Objective Therefore, we assessed the feasibility of TAD for differential diagnostics by classifying between ASD and BPD in this proof-of-concept study. Methods We collected a rich multimodal dataset of reciprocal interactions, specifically dyadic conversations (n=120 interaction partners). From this data, we extracted more than 800 features, allowing us to capture the core area of defining symptoms for both conditions: social interactions. These features include speech patterns, facial expressions, movement quantity and interpersonal synchrony. We used these features to train and stack linear support vector machines to classify between ASD-involved, BPD-involved and comparison interaction partners. Findings Base models capturing facial expressions during speaking and listening, speech patterns, synchronisation of facial expressions and movement quantity all performed above chance when differentiating between ASD-involved and BPD-involved interaction partners. Stacking all base models containing conceptually related features further increased accuracy, with our algorithm achieving nearly 82% of balanced accuracy, solely based on 20 min of conversation. Conclusions Our proof-of-concept study shows the immense potential of TAD for differential diagnostics: data collection only requires microphones and webcams while feature-extraction is automated, making this approach highly objective, scalable and user-friendly. Clinical implications Our TAD algorithm shows the potential of multimodal, behavioural data for differential diagnostics. On the basis of clinical validation such an algorithm has the potential to streamline differential diagnoses of ASD in the future, enabling faster and more accurate diagnostic assessment and ultimately reducing patient distress by shortening the wait for an appropriate treatment plan.

Background Data on antipsychotic use for the Swedish paediatric population is limited. Objective We assessed the incidence, likely indication and extent of off-label antipsychotic use among children and adolescents in Sweden. Methods In this nationwide register-based study, individuals younger than 18 years with at least one antipsychotic dispensing between 1 January 2008 and 31 December 2021 were identified. Yearly age-standardised and sex-standardised incidence per 1000 persons was estimated and temporal trends were assessed using Poisson log-linear regression. We also assessed the likely indication and the proportion of on-label and off-label use. Findings Among 4 108 171 individuals who were children or adolescents at some point during the study period, 24 742 initiated antipsychotic treatment at least once, contributing 25 576 incident dispensings during the study period. Incidence increased from 0.48 to 1.28 per 1000 persons (risk ratio, RR per year 1.08, 95% CI 1.05 to 1.11; cumulative increase 180%), with a more pronounced rise in females (0.43 to 1.51 per 1000; RR 1.11, 95% CI 1.10 to 1.12; 284%) than males (0.53 to 1.06 per 1000; RR 1.06, 95% CI 1.05 to 1.07; 113%), driven by adolescents aged 12–17 years. The largest drug-specific increases were observed for quetiapine (0.04 to 0.33 per 1000; RR per year 1.18, 95% CI 1.17 to 1.19; cumulative increase 804%) and aripiprazole (0.03 to 0.36 per 1000; RR per year 1.16, 95% CI 1.14 to 1.18; cumulative increase 608%). A likely indication was identified in 64.3% (n=16 455) of incident dispensings, most commonly autism spectrum disorder (15.4%), attention-deficit hyperactivity disorder (10.9%) and anxiety disorders (9.6%). Among those with an identifiable indication, 81% were dispensed off label, mainly due to non-approved indications (64.8%) and most frequently among adolescent females. Conclusions In the paediatric population in Sweden, incidence of antipsychotic use increased between 2008 and 2021, especially among adolescent females and most incident dispensing with an identifiable indication were off label, underscoring the need to evaluate the long-term effectiveness and safety of antipsychotics in children and adolescents. Clinical implications These patterns highlight the need to evaluate the long-term effectiveness and safety of antipsychotics in children and adolescents.

Background Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. Objective Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. Methods Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011–2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. Findings Discontinuation rates varied widely (children 19%–61%, adolescents 37%–68%, young adults 52–67%, adults 38%–68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32–1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. Conclusions Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. Clinical implications Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.

Background Recurrent self-harm is common and is associated with an increased risk of unnatural death including suicide and fatal accidents. We developed and validated prognostic models to stratify individuals by risk of unnatural death after healthcare presentation for non-fatal self-harm to support clinical decision-making and targeted prevention when capacity to deliver evidence-based intervention is limited. Methods We used insurance claims and vital registration data from 6846 South African medical insurance beneficiaries aged ≥10 years who were discharged alive after healthcare presentation for self-harm during 2011–2021 to develop and validate models predicting unnatural death after non-fatal self-harm. We fitted competing-risk regression models to predict unnatural death within 1–3 years after presentation and discharge. Variable selection was guided by the least absolute shrinkage and selection operator. We used bootstrapping for internal validation and estimated optimism-corrected concordance indices (C-index), calibration intercepts and slopes, and for risk stratification the proportions of unnatural deaths captured across predicted-risk groups. Final models included age, sex, encounter characteristics, prior psychotropic medication use and selected prior mental disorder diagnoses. Results The final models achieved optimism-corrected C-indices of 0.74 at presentation and 0.75–0.76 at discharge and identified 86–88% of observed unnatural deaths within 2 years among the 40% of individuals with the highest predicted risk. Models showed little evidence of systematic miscalibration (optimism-corrected calibration intercepts –0.02 to –0.01), but some overfitting (optimism-corrected calibration slopes 0.84–0.92). Using the model with the highest optimism-corrected C-index, the simplified discharge model, the observed 2-year risk of unnatural death was 0.15% (95% CI 0.06% to 0.32%) among the 60% of individuals with the lowest predicted risk, comparable to the risk among 1 249 760 individuals without a self-harm history (0.14%, (95% CI 0.14% to 0.15%)). Conclusions The prediction models effectively rank individuals accessing private sector care in South Africa by their probability of unnatural death following healthcare presentation for non-fatal self-harm. Clinical implications The models are intended to support clinical decision-making and guide the prioritisation of individuals with predicted high risk for targeted interventions, supporting more efficient allocation of mental health care capacity, which is often limited in low- and middle-income settings.

Background Children and young people (CYP) with neurodevelopmental diagnoses such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have high child and adolescent mental health service (CAMHS) needs. Mood instability is a common and impairing emotion dysregulation-related symptom linked to increased adult psychiatric service use; however, its role in CAMHS trajectories remains unclear. We aimed to examine whether baseline mood instability was significantly associated with time to discharge and annual CAMHS use in CYP with ASD and/or ADHD. Methods We applied natural language processing (NLP) to extract mentions of mood instability within 3 months of ASD or ADHD index diagnosis from electronic health records of 21 906 CYP referred to CAMHS between 2008 and 2022. We used accelerated failure time models and negative binomial regression to assess associations between baseline mood instability and time to discharge and annual CAMHS use, adjusting for clinical and sociodemographic confounders. Findings Mood instability was associated with increased annual CAMHS use across ASD (adjusted incidence rate ratio (aIRR) 1.24, 95% CI 1.08 to 1.42), ADHD (aIRR 1.47, 95% CI 1.30 to 1.67) and ASD+ADHD (aIRR 1.27, 95% CI 1.12 to 1.44) groups. While mood instability had no significant effect on discharge timelines in autistic children with or without ADHD, it was linked to reduced time to discharge in the ADHD group (aTR 0.76, 95% CI 0.69 to 0.84). Associations were most pronounced in those not receiving ADHD medication in the ADHD group (aIRR 1.67, 95% CI 1.47 to 1.89; aTR 0.70, 95% CI 0.61 to 0.79). Conclusions Mood instability was significantly associated with elevated CAMHS use in CYP with neurodevelopmental conditions, with differential effect across diagnostic groups. This may reflect both variations in clinical expression of mood instability and configuration of neurodevelopmental CAMHS provision. Clinicalimplications These findings suggest the importance of assessing emotion dysregulation in care planning and pathway allocation in neurodevelopmental CAMHS. NLP offers a time- and cost-efficient approach to surface and structure clinical data from electronic CAMHS records for scalable clinical research on complex constructs such as mood instability.

Background Black people experience persistent inequalities in mental health outcomes, access and care quality compared with their white counterparts. These disparities are compounded by structural racism and a lack of culturally competent care within National Health Service (NHS) services. Creative arts therapies (CATs), including music, art, dance and drama therapy, may offer culturally relevant, non-verbal approaches to mental health support for this population. Objective To explore how black young people with mental health challenges and NHS clinicians perceive the usefulness and cultural relevance of CATs and to examine their potential as culturally competent interventions for improving mental well-being. Methods A qualitative, multicentre study was conducted across five NHS Trusts in England. 20 black service users (aged 16–24) and 15 clinicians participated in 10 online focus groups (45–60 min each). Transcripts were analysed thematically using Braun and Clarke’s six-step thematic analysis method constructed with NVivo V.12 software. Coding was led by the first author, with regular discussions with a second researcher to refine interpretations and develop themes. Findings Five overarching themes were identified: (1) creative arts as vehicles for emotional healing, identity and agency, (2) challenges and barriers to CAT implementation, (3) disconnection and mistrust within clinical encounters, (4) discovering therapeutic potential through creative experience and (5) creative expression as a bridge between culture and care. Participants viewed CATs as emotionally regulating, accessible and aligned with black cultural identity though limited by underfunding, stigma and insufficient cultural competence within the NHS. Conclusions CATs may provide a culturally congruent and emotionally accessible approach to mental healthcare for black youth. Embedding culturally competent, creative modalities within NHS pathways could enhance engagement, trust and equity in service outcomes. Clinical implications CATs should be integrated early in NHS pathways (eg, Child and Adolescent Mental Health Services, Talking Therapies) to improve engagement among black youth who may be hesitant to engage in verbally dominant therapies. However, scaled implementation requires meaningful coproduction with black communities, cultural competence training for multidisciplinary teams and recognition within NHS and National Institute for Health and Care Excellence frameworks.

Background Evidence on ethnic differences in depression in the UK is mixed, and the suitability of current screening tools is under question. Objective To examine ethnic differences in depression identification, symptom reporting and phenotypes among middle-aged and older adults in the UK. Methods We assessed lifetime depression in 502 140 UK Biobank participants using an established algorithm. Depression symptoms were assessed using the Composite International Diagnostic Interview-Short Form data from the 2022 mental health follow-up. Latent class analysis (LCA) identified depression phenotypes. Logistic regression models adjusted for age, sex, deprivation and physical health assessed ethnic differences in depression identification, symptom reporting and phenotype membership. Findings Overall, 23.7% of participants met study criteria for a lifetime history of depression. Compared with White participants, depression identification was significantly lower in all ethnic minority groups except the mixed group. Black, other Asian and South Asian participants were less likely to report core depression symptoms (prolonged sadness or loss of interest). LCA produced four phenotypes: major depression, somatic depression, non-somatic depression and subthreshold depression. Black (adjusted OR (aOR) 1.70, 95% CI 1.32 to 2.20), other Asian (aOR 1.73, 95% CI 1.21 to 2.46) and South Asian (aOR 1.63, 95% CI 1.26 to 2.10) participants were more likely than White participants to belong to the somatic depression phenotype. Conclusions Lower rates of depression identification among ethnic minority groups may reflect limitations in how depression is defined, perceived and detected within these populations. Clinical implications Depression may present more somatically in some ethnic minority groups. Clinicians may need to adopt more culturally informed assessment approaches to ensure accurate detection and appropriate support.

Recently, a proposal was made to de-implement ineffective or harmful psychotherapeutic treatments from the healthcare system. Given the potential wide-ranging implications of this proposal, a critical review is warranted. As an example of an ‘implementation failure’, the authors of the proposal discussed non-trauma-focused treatments of post-traumatic stress disorder (PTSD). For this reason, we reviewed the evidence for non-trauma-focused psychotherapies compared with trauma-focused or exposure-based psychotherapies of PTSD in adults, published in the recent 7 years. We focused on efficacy and safety as the central criteria for potential (de-)implementation. The majority of meta-analytical results showed non-trauma-focused psychotherapies to be non-inferior to trauma-focused psychotherapies. In only a few analyses, non-inferiority was not found or exposure therapy achieved statistically significantly better effect sizes, which, however, were small and not clinically significant. Furthermore, non-trauma-focused psychotherapies were found to be safe and well-tolerated with low dropout. Hence, key criteria for de-implementation are not met. The results question the claim that non-trauma-focused therapies constitute an implementation failure. Thus, the example of trauma-focused versus non-trauma-focused psychotherapy of PTSD highlights fundamental problems associated with the proposal to de-implement specific treatments from the healthcare system. The reviewed results suggest that researcher allegiance may have an important impact on (de-)implementation decisions and needs to be rigidly controlled for. Several open questions remain, including consented criteria on which de-implementation decisions would be based, who decides about the actors responsible for making these decisions and, crucially, the mechanisms by which those in positions of authority are held accountable.

Background Patients in forensic psychiatric care (FPC) are often treated with various psychotropic medications. However, evidence regarding their effectiveness in this setting is lacking. Objective The study aimed to estimate how different psychotropic medications are associated with the use of coercive measures and recidivism during FPC. Methods In this observational national register-based study, we included all patients newly registered as admitted to FPC in Sweden between January 2009 and August 2024. Exposures included major classes of psychotropic medication (typical antipsychotics, atypical antipsychotics, antidepressants, hypnotics and sedatives, antiepileptic medications, opioids, medications for addictive disorders and mood stabilisers), antipsychotic treatment strategies (no use, monotherapy, polypharmacy, long-acting injectables or clozapine) and specific antipsychotic agents. Outcomes were the use of coercive measures and recidivism into criminal behaviour. We performed a within-individual analysis using conditional generalised estimating equation models, where the risk of outcomes was compared between exposed and non-exposed time periods. Findings In total, 2690 patients were included, of which 25.1% experienced at least one occasion of coercion and 27.1% at least one event of recidivism during FPC. Atypical antipsychotics were associated with a reduced risk of subsequent use of coercive measures (OR 0.70, 95% CI 0.55 to 0.89) and recidivism (OR 0.79, 95% CI 0.63 to 0.99). Medication for addictive disorders was associated with a reduced risk of coercive measures by 34% (OR 0.66, 95% CI 0.47 to 0.93). Among antipsychotic agents, clozapine was associated with the largest risk reduction in the use of coercive measures (OR 0.48, 95% CI 0.33 to 0.69) and recidivism (OR 0.49, 95% CI 0.33 to 0.74). There was no significant difference between long-acting injectable, oral monotherapy or polypharmacy. Conclusions We observed that atypical antipsychotics, especially clozapine, were associated with a risk reduction for coercive measures and recidivism during FPC. Additionally, medications for addictive disorders were associated with a reduced risk of coercive measures. Clinical implications Our results can help inform decision-making processes in this clinical setting regarding pharmacotherapy but should be interpreted as one of many aspects influencing treatment success in FPC.

Background Depression is closely linked to neuroinflammation, and in chronic kidney disease, the accumulation of uremic toxins (UTs) may promote neuroinflammatory processes through the activation of inflammatory pathways. Objective The objective of this longitudinal study was to evaluate the association between UTs and depressive symptoms in a large, well-characterised cohort of non-dialysed adults with chronic kidney disease, a population in which this relationship had not yet been investigated. Methods The Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort comprised 3033 CKD stage 2–5 patients with 5 years of follow-up. Changes over time in depressive symptoms were assessed on the Center for Epidemiologic Studies Depression (CESD) scale. Mixed models were used to examine associations between the change in the CESD score and baseline levels of the UTs phenylacetylglutamine (PAG), indoxyl sulphate (IS), indole-3-acetic acid (IAA), p-cresyl sulphate, kynurenine, kynurenic acid and trimethylamine N-oxide. Findings 2165 patients were included (median age: 68 years; mean estimated glomerular filtration rate (eGFR): 35 mL/min/1.73 m²; median baseline CESD score: 7; mean follow-up time: 4.0 years). After adjustment for confounders, the CESD score was found to have increased by 0.11 (0.04 to 0.18) points per year. A doubling in PAG level was associated with an additional increase of 0.06 (0.01 to 0.18) points per year in the CESD. A doubling in IS and IAA levels was associated with a higher mean CESD score (0.20 (0.01 to 0.39) for IS and 0.28 (0.05 to 0.50) for IAA) but not with the score’s change over time. Conclusion PAG was significantly associated with changes in CESD score over time. Higher IS and IAA levels were linked to higher mean scores. Further studies are needed to confirm these results and to determine whether lowering serum UT levels would help to manage depressive symptoms in patients with CKD. Clinical implications Further research is needed to clarify the role of UTs; a better understanding could uncover novel metabolic pathways and inform new therapeutic strategies to complement the management of depressive symptoms.

Background The existent classifications of the distinct evidence-based psychological interventions (EBPs) are broad, not systematically developed or restricted to one mental disorder. Objective To identify the unique EBPs and their variations evaluated for six severe mental disorders (schizophrenia and psychosis, bipolar disorders, bulimia nervosa, anorexia nervosa, one type of substance use and borderline personality). Study selection and analysis We established a large cohort of EBPs by selecting all randomised controlled trials (RCTs) from six recent and large network meta-analyses for severe mental disorders in adults. Pairs of researchers independently selected all psychological intervention arms and assigned them to macro-families based on labels and theoretical background. Subsequently, within each macro-family, groups of identical arms, that is, referencing the same manual or protocol, were consolidated as distinct psychological interventions. Adaptations related to content, structure, delivery or culture were also described. Findings From 260 RCTs, 422 psychological intervention arms were grouped in 45 macro-families and reduced to 266 distinct interventions (63% of total arms) across disorders. Intervention variability, that is, the proportion of unique psychological interventions out of the total number of arms, was lowest for the substance use disorder selected—stimulant use disorder (47/104, 45%) and bulimia nervosa (25/45, 55.5%). Variability was high for bipolar disorders (48/59, 81%), anorexia nervosa (20/29, 69%), schizophrenia/psychosis (86/123, 70%) and borderline personality disorder (40/62, 64.5%). 79 of the 266 distinct interventions (29%) contained adaptations (12% multiple adaptations) and 75/266 (28%) had openly available manuals or protocols. Conclusions and clinical implications Mapping EBPs across macro-families and distinct interventions could inform evidence synthesis and identification of active ingredients, guide mechanisms of change exploration and support prioritising interventions for research and dissemination.

Background Suicidal ideation (SI) is a major global concern, yet its dynamic interplay with other symptoms remains poorly understood. Objective To identify symptoms that co-fluctuate with or temporally precede SI to better understand symptom dynamics. Methods Longitudinal data from three Dutch psychiatric cohorts with lifetime internalising disorders (16 waves from April 2020 until February 2022) were collected during the COVID-19 pandemic. We analysed depressive, happiness, anxiety, loneliness, worry symptoms and COVID-19-specific items only in those participants with SI fluctuations. Dynamic time warping (DTW) quantified within-person similarity between symptom trajectories and SI and results were aggregated at the group level. Findings 307 participants (mean age 44.8 years; 61.6% female) showed increasing SI over time (p<0.001). In the undirected analysis, SI aligned with four depressive symptoms (ie, sad mood, low self-esteem, low interest and reduced happiness), two anxiety-related symptoms (ie, fear of losing control, faintness) and overwhelming worrying, whereas the interpersonal symptoms feeling abandoned and feeling lonely did not survive false discovery rate (FDR) corrections. In directed analysis, while sad mood, hypersomnia, numbness and worrying about projects initially demonstrated temporal precedence, no directed lead-lag relationships survived FDR correction. Conclusion SI is embedded in a broad symptom network beyond depression. These results underscore the value of time-sensitive, idiographic monitoring using tools like DTW to capture the person-specific temporal pathways through which SI emerges and intensifies. Clinical implications This study suggests a core group of affective, cognitive and distress-related symptoms that could serve as informative signals for evaluating changes in SI and may represent actionable targets for intervention.

Background External validations of existing risk models are efficient steps towards potential implementation, avoiding the need to develop new models. However, validation in new clinical settings poses several challenges. Objective To 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. Methods We selected episodes of self-harm (International Classification of Diseases, Tenth Revision codes X60–X84; Y10–Y34) by individuals 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 individual’s suicide risk within 12 months after their index self-harm. We assessed model performance using discrimination (Harrell’s concordance index (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. Findings We identified 16 130 individuals who presented to hospital with self-harm, of whom 106 (0.7%) died by suicide in the 12-month follow-up period. The OxSATS model showed good discrimination in external validation (c-index 0.73, 95% CI 0.68 to 0.79). 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 0.77 to 1.25). Conclusions Despite 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. Clinical implications OxSATS may help clinicians assess suicide risk after self-harm by providing structured and transparent estimates as part of a comprehensive clinical assessment. Structured risk assessment tools may support identification of individuals who could benefit from additional risk management procedures, such as closer monitoring and follow-up or referral to specialist services, particularly in settings with limited access to such services.

Background Self-harm in young people is associated with elevated risks for subsequent self-harm, suicide attempts and suicide, particularly during the first year. Yet the trajectory across sex, age and self-harm methods remains poorly understood. Objective To estimate risk for subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm event in young people. Methods This study included 77 647 individuals (57.0% female) whose first hospital-treated (ie, within inpatient or outpatient specialised healthcare) self-harm episode occurred between ages 10–24 years during 1973–2019. We estimated cumulative incidence and incidence rate for subsequent self-harm, suicide attempts and suicide at 1 month, 3 months and 1 year following the initial episode. Findings Within 1 year, the cumulative incidence was 17.3% (95% CI 17.0 to17.5) for subsequent self-harm, 8.3% (8.1 to 8.5) for suicide attempt and 0.3% (0.2 to 0.3) for suicide. The highest risks occurred in the first month: 8.4% (8.2 to 8.6) for self-harm, 2.9% (2.8 to 3.0) for suicide attempt and 0.04% (0.03 to 0.05) for suicide. In the first month, the incidence rate of self-harm was 2.97 per 1000 person-days (2.90 to 3.05), falling to 0.55 (0.54 to 0.56) over the year. The suicide attempt rate declined from 0.98 (0.94 to 1.02) to 0.24 (0.24 to 0.25) and the suicide rate from 0.013 (0.009 to 0.019) to 0.007 (0.006 to 0.008). Males exhibited the highest suicide risk and females the highest attempts risk. First-month self-harm risk was greatest among males and children aged 10–12. Conclusions The month following a self-harm episode is marked by an elevated risk of subsequent self-harm, suicide attempts and suicide, yet risk remains elevated over the full year. Clinical implications These findings underscore the need for both acute and sustained prevention efforts. Special attention should be given to males and children aged 10–12 presenting with self-harm of ambiguous intent, as their risk of repetition may otherwise go unrecognised.

Background Digital psychotherapies may offer scalable options for depression, but most randomised controlled trials (RCTs) are at moderate or high risk of bias. Mapping the methodologies, populations, interventions and outcomes of completed, ongoing and terminated/withdrawn RCTs of digital psychotherapies for depression could help anticipate future evidence gaps and redundancies. Study selection and analysis We conducted a systematic scoping review of RCTs registered in the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, European Union Clinical Trials Register and European Union Clinical Trials Information System between 2018 and 2025. Eligible RCTs evaluated digital psychotherapies for adults with depressive disorders, bipolar depression or depressive symptoms. Extracted data encompass methodological features, population characteristics, settings, description of intervention, control, funders, registration timing and reporting practices. Findings Among the 681 RCTs, 51.8% were completed, 34.1% published their results, 78.1% were prospectively registered and 8.5% were industry funded. Multicentre RCTs accounted for 23.1%, with 42.9% being planned in the USA, Germany or Canada and 25.1% recruiting in low- or middle-income countries. Inclusion relied on self-reported symptoms only for 61.5% and suicidal ideation was an exclusion criterion in 61.8%. The most frequent type of digital psychotherapy was cognitive-behavioural therapy for 64.6%. Human support was a component of the intervention in 44.2%. Chatbots were assessed by 4.6%. Waitlist control was used in 21%, with 49.3% of RCTs being open-label. The most frequent primary outcome was the Patient Health Questionnaire-9 for 35.7%. Conclusion Strengthening future evidence on digital psychotherapies requires timely dissemination of results, use of active controls, diversifying assessed psychotherapies and studying efficacy in populations with limited access to psychotherapy.

Background Until June 2025, individuals initiating clozapine in the USA were required to undergo routine haematological testing in accordance with the Clozapine Risk Evaluation and Mitigation Strategy (REMS) programme. Although the Clozapine REMS programme was eliminated in June 2025, clinical and prescribing recommendations on testing remained intact. Little is known, however, about adherence to testing requirements in practice. Objective The aim of this study was to assess the prevalence and frequency of haematological testing in patients on clozapine. Methods A cohort study using three US health insurance claims databases (1 January 2000–31 March 2022) assessed (1) proportion of individuals with at least one haematological test (white blood cell count with differential) prior to clozapine initiation and (2) frequency of testing (number of tests per 30 days of follow-up) during months 0–6, 7–12 and 13–24 of clozapine therapy. Tests were identified based on billing codes; patients hospitalised during the assessment period were assumed to have received testing. Findings A total of 62 003 clozapine initiations (mean (SD) age, 36 (15) years; 57% male) were identified, of which 71% were preceded by testing within 60 prior days. The mean (SD) testing rate while on therapy was 2.2 (1.8) tests per patient for each 30-day period during the first 6 months of treatment, 2.0 (1.8) tests per 30 days during months 7–12 and 1.5 (1.4) tests per 30 days during months 13–24. Conclusions In this study of individuals initiating clozapine in the USA, haematological testing was completed at a lower-than-expected rate prior to clozapine initiation and during the first 6 months of treatment but was in accordance with testing requirements thereafter. Clinical implications Although clozapine drug labelling recommends routine haematological testing, especially during the first 6 months of treatment, such testing may not consistently occur. Reasons for less-than-recommended testing frequency should be further investigated.

Background Generative artificial intelligence (AI) use has been suggested to have adverse mental health consequences but a causal relationship has not been examined. Objective To simulate a randomised controlled trial of AI use in a work, school or personal context by applying target trial emulation to multiple waves of data from a nationally representative survey. Methods We conducted a target trial emulation using non-probability survey data from three waves of a nationally representative survey conducted between 18 June 2024 and 8 January 2025. Participants aged ≥18 years reported generative AI use frequency at baseline. High-frequency use was defined as multiple times per week or more. The primary outcome was depressive symptom severity measured using the Patient Health Questionnaire 9-item (PHQ-9) at follow-up. Generalised causal forests assessed heterogeneity of treatment effects. Findings Among 19 099 participants assessed at baseline, 2862 (15.0%) reported AI use at least multiple times per week. A subset of 3109 (16.3%) returned for follow-up. In the primary weighted analysis, high-frequency use was not significantly associated with change in PHQ-9 score at follow-up (mean difference –0.18, 95% CI –0.94 to 0.59; p=0.65). Multiple sensitivity analyses using alternate outcome definitions also did not identify significant causal effects. Generalised causal forests yielded no significant evidence of heterogeneity of effect (p=0.81). Conclusions In an emulated randomised trial among US adults, generative AI use was not associated with subsequent depressive symptoms. This result does not support the premise that AI use causes greater depressive symptoms, although adverse outcomes among vulnerable individuals cannot be excluded. Clinical implications AI use is unlikely to cause increased depressive symptoms among most US adults. Continued monitoring should clarify potential risks among vulnerable populations.

Background Adolescent depression is a major public health concern with limited access to effective treatments. Behavioural activation (BA) is a suitable intervention for digital delivery, but definitive adolescent trials are scarce. Objective To evaluate whether therapist-guided and self-guided internet-based BA (I-BA) are more efficacious and cost-effective than treatment as usual (TAU) for adolescents with mild to moderate major depressive disorder (MDD). Methods Single-blinded, parallel-group randomised controlled trial with economic evaluation. A total of 219 adolescents (13–17 years) with mild-moderate MDD were randomised (1:1:1) to 10 weeks of therapist-guided I-BA, self-guided I-BA or TAU. Both I-BA interventions included adolescent and parent modules. Primary outcome: change in depression severity (Children’s Depression Rating Scale-Revised, CDRS-R, range 17–113) from baseline to 3-month follow-up (primary endpoint), assessed by blinded evaluators. Analyses included all randomised participants, with statisticians blinded to allocation. A health economic evaluation was performed at the primary endpoint. Findings Baseline CDRS-R indicated clinically significant depression (mean 57.1, threshold ≥40). Retention at the primary endpoint was 82.6%. Mean reductions were 17.0 (therapist-guided I-BA), 16.0 (self-guided I-BA) and 11.6 (TAU), bringing both I-BA groups below the clinical cut-off. Therapist-guided I-BA showed greater reductions than TAU (estimated mean difference –4.68; 95% CI –0.05 to –9.30; p=0.048, d=–0.47; 95% CI 0.00 to –0.93), while self-guided I-BA was not statistically superior (estimated mean difference –3.44; 95% CI –8.05 to 1.17, p=0.14, d=–0.37; 95% CI –0.86 to 0.12). The predefined six-point clinical important difference was not met. Results were sensitive to modelling: significance disappeared with random slopes but effect estimates were similar; baseline-adjusted analyses favoured both I-BA arms. Both I-BA options had lower costs than TAU (p=0.03, p<0.001), with self-guided I-BA being the most economical. Conclusions Therapist-guided I-BA reduced depressive symptoms at lower cost than TAU, but clinical importance and robustness are uncertain. Self-guided I-BA showed no clear superiority but was cost-efficient. Clinical implications Therapist-guided I-BA may increase access to evidence-based care for adolescents with MDD, though findings require cautious interpretation. Self-guided I-BA may be useful where therapist access is limited, but more research is needed.

Background International students experience a high mental health burden and face barriers to accessing and sustaining support, yet domain-level stress frameworks provide limited guidance on which specific stressors should be prioritised. Objective To prioritise item-level stressors associated with perceived stress and mental well-being among international students using machine-learning models, and to evaluate cross-site transportability via external testing between Chinese students in the UK and international students in China. Methods We conducted a cross-sectional online survey of 481 students across two sites, Chinese students in the UK and international students in China. Item-level stressors, perceived stress (PSS 10) and mental well-being (Warwick–Edinburgh Mental Wellbeing Scale; WEMWBS) were assessed. Elastic net and random forest models were evaluated using nested cross-validation, and cross-site external testing was conducted by training in one site and testing in the other. Findings Across the six models, random forest explained approximately 22%–35% of the variance in perceived stress and 25%–27% of the variance in mental well-being. Concerns about mental well-being, sleep difficulties, physical health and family or self-imposed academic expectations consistently ranked highly across sites. Social isolation and restricted social life were strongly associated with lower mental well-being. Context-specific stressors also emerged: in the UK setting, greater time-management pressure, low confidence in interacting with others and loneliness were more strongly associated with poorer outcomes, whereas in the Chinese setting, difficulties balancing study and personal life and not knowing where to seek help played a larger role. Cross-site validation indicated that a substantial portion of the item-level stressor signal generalised across settings. Conclusions Item-level stressor profiles provide informative, partly generalisable evidence on stressors linked to international students’ mental health. The identified high-impact stressors offer concrete, context-sensitive targets for prevention and intervention in university mental health services. Clinical implications These findings can inform how university mental health services prioritise support and prevention by focusing on core stressors while adapting provision to locally salient challenges.

Background Large language models (LLMs) are rapidly entering clinical and consumer use, yet their probabilistic outputs have delivered a variety of unsafe user responses. Difficulties in quantifying and mitigating risks posed by LLMs threaten to stall regulatory evaluation and clinical deployment of LLM-based software as a medical device (LLM-SaMD). Practical approaches are needed to extend existing medical-device regulations to LLM-SaMDs. Objective To demonstrate how simulation can extend existing medical-device risk management frameworks for addressing LLM-SaMD-specific risks. Methods We implement a simulation-based methodology for estimating LLM-SaMD risk. Fourteen open-source models were evaluated on three safety-classification tasks: suicidal-ideation, therapy-request and therapy-like interaction detection. Synthetic datasets were generated by Gemini 2.5 Pro and evaluated by psychiatrists. Model false-negative rates informed estimates of P1, the likelihood that a hazard progresses to a hazardous situation, and P2, the likelihood that that situation results in harm. Findings LLM success at generating synthetic datasets varied by task, with strong performance for neutral and non-therapeutic content but frequent errors in suicidal-ideation and therapy-like interactions. Performance generally improved with model size. Estimated P1 values ranged from 1.1x10–⁸ to 1.6x10–⁴ and P2 from 4.9x10–⁵ to 5.1x10–3, spanning four orders of magnitude. Conclusions By linking model failure modes to structured pathways to harm, simulation can extend existing medical-device risk frameworks to help address the probabilistic and context-dependent risks of LLM-SaMDs. Clinical implications Simulation-based risk estimation offers a practical way to characterise the risk landscape for specific LLM-SaMD, patient population and clinical context combinations.

Background People with severe mental illness (SMI) have a higher risk of infection-related hospitalisations than the general population, yet the reasons why remain poorly understood. Objective We aimed to identify factors associated with infection-related hospitalisations and to explore how these factors cluster together within the patient population. Methods We conducted a retrospective cohort study using linked electronic health records from a large secondary mental health service in South London. Individuals with an SMI diagnosis between 1 January 2007 and 31 December 2019 were included. Cox regression models examined associations between a wide range of sociodemographic, health-related, clinical and treatment and service-use factors and time to first infection-related hospitalisation. Significant factors were then used in a hierarchical cluster analysis to identify distinct patterns. Findings In 19 995 individuals with SMI, several factors associated with infection-related hospitalisations emerged, with the strongest being number of general hospital admissions for ambulatory care sensitive conditions (HR=2.31, 95% CI 2.08 to 2.56), clozapine prescribing (HR=1.67, 95% CI 1.45 to 1.92) and severe problems with physical illness/disability (HR=1.36, 95% CI 1.31 to 1.42). Two distinct patterns emerged: one characterised by older age, dementia and poor physical health; the other by younger age with complex psychiatric needs and use of alcohol and other substances. Conclusions1 This study identified several factors associated with infection-related hospitalisations and highlighted how these factors tend to group together among people with SMI. Clinical implications These findings indicate potential areas where tailored prevention and monitoring strategies may be warranted to help reduce the likelihood of infection-related hospitalisation in people with SMI alongside broader measures such as prioritisation for pneumococcal and influenza vaccination.

Background It is unclear whether acute infections associated with short-term systemic inflammation influence the risk of severe mental illness (SMI). Objective To investigate relationships between acute infections and incident SMI using electronic health records from the UK. Methods Using data from the Clinical Practice Research Datalink Aurum (1 January 2007 to 15 June 2024), we conducted six matched cohort studies. Adults (≥18 years) with gastroenteritis (GE), lower respiratory tract infection (LRTI), skin and soft tissue infection (SSTI), urinary tract infection (UTI), sepsis and meningitis/encephalitis (positive control exposure) recorded in primary care were matched with up to five individuals without infection on age, sex and practice in calendar date order and followed for incident SMI (schizophrenia, bipolar disorder, other psychoses). We estimated HRs for SMI comparing those with and without each infection using Cox regression, stratified by match set, adjusting for potential confounders (deprivation, Charlson Comorbidity Index, alcohol, smoking, body mass index and ethnicity). Findings Our six study cohorts ranged from 2 089 168 adults (391 773 with SSTI, 1 697 395 without) to 106 155 (17 860 with meningitis/encephalitis, 88 295 without). Median follow-up ranged from 4.1 years (IQR 1.9–6.9) in the sepsis cohort to 5.7 years (IQR 2.6–9.8) in the meningitis/encephalitis cohort. After adjustment, each infection was associated with increased SMI risk: SSTI, HR 1.16 (95% CI 1.08 to 1.24); LRTI, 1.28 (95% CI 1.20 to 1.38); UTI, 1.44 (95% CI 1.31 to 1.58); GE, 1.53 (95% CI 1.42 to 1.65); sepsis, 1.69 (95% CI 1.52 to 1.88); and meningitis/encephalitis, 3.36 (95% CI 2.61 to 4.32). Conclusion Our findings suggest SMI risk is higher among adults with a range of acute infections compared with those without, with higher risks for the more severe infections meningitis/encephalitis and sepsis. Clinical implications Providing timely infection treatment, targeted mental health support following severe infections, and where appropriate offering relevant vaccinations, may limit SMI risk.

Background Poor persistence and adherence to attention-deficit/hyperactivity disorder (ADHD) medication is a significant barrier to effective long-term care, particularly during adolescence, yet age-specific and sex-specific trajectories remain poorly characterised. Objective To characterise medication initiation, discontinuation and long-term adherence patterns for children and adolescents diagnosed with ADHD in a real-world setting. Methods A nationwide retrospective cohort study, including 8961 children and adolescents (aged <18 years) with a new ADHD diagnosis in child and adolescent mental health services between 1 January 2010 and 31 December 2012, with follow-up until 31 December 2021. Main outcomes were medication initiation rates; time to first medication discontinuation, analysed using Kaplan-Meier estimates and restricted mean survival time at 1 year and longitudinal adherence, measured by the proportion of days covered over 9 years. Findings Of the 8961 individuals in the cohort (mean age at diagnosis, 12 years; 69% male), 6661 (74.3%) initiated medication, with a median time from diagnosis to initiation of 106 days (IQR 17–231); 55% initiated within 90 days. Discontinuation increased significantly with age; adolescents aged 15–17 years remained on treatment for 31.9 fewer days (95% CI –40.8 to –23.1; p<0.001) in the first year compared with children aged 5–11 years. Females also discontinued significantly earlier than males (difference –13.2 days; 95% CI –19.8 to –6.5; p<0.001). Longitudinal analysis confirmed that older age at initiation and female sex were associated with a significantly steeper decline in medication coverage over time. Conclusions Discontinuation and low adherence to ADHD medication were common and increased substantially through adolescence, with females at higher risk of early cessation. Clinical implications Late adolescence warrants closer clinical monitoring and shared decision-making to support appropriate treatment continuation or well-informed discontinuation, particularly for older adolescents and females. Integrating structured transition planning and attention to sex-specific barriers may help reduce avoidable non-adherence during this high-risk period.

Background Suicide remains a leading preventable cause of death, and patients presenting with self-harm constitute a high-risk group. The Oxford Suicide Assessment Tool for Self-Harm (OxSATS) is a validated model estimating suicide risk. While its statistical performance is established, its clinical utility remains unexplored. Objective To understand clinicians’ views on the feasibility, acceptability and potential workflow integration of OxSATS. Methods Semistructured interviews with 15 multidisciplinary National Health Service clinicians explored current suicide risk assessment practice, experience with structured tools and views on OxSATS. Participants applied OxSATS to standardised vignettes to simulate real-world decision-making. Interviews were analysed using reflexive thematic analysis. Findings Clinicians valued OxSATS for its simplicity, objectivity and percentage-based outputs. OxSATS was viewed as promoting a shared language around suicide risk and supporting assessment consistency. Alignment between OxSATS estimates and clinical judgement was good. However, some clinicians perceived the tool as underestimating risk associated with violent methods. Key implementation barriers included limited scope for wider psychosocial context and potential over-reliance on the tool by inexperienced clinicians. Participants emphasised that OxSATS should complement, not replace, clinical formulation and highlighted the need for clear guidance to support adoption. Conclusion OxSATS was viewed as a promising adjunct to suicide risk assessment following self-harm. Addressing concerns around scope, interpretation of percentage risk and integration into wider suicide risk training will be key to successful implementation. Clinical implications This study highlights clinicians’ interest in evidence-based adjuncts to suicide risk formulation and supports the use of probability-based models to enhance decision-making.

Background Pharmacological augmentation is commonly used for patients with major depressive disorder (MDD) who respond inadequately to antidepressant treatment. However, the robustness of evidence supporting lithium, second-generation antipsychotics (SGAs), and triiodothyronine (T3) augmentation for MDD remains uncertain. Objective To reappraise the efficacy and robustness of evidence for pharmacological augmentation strategies for MDD, focusing on lithium, SGAs, and T3. Study selection and analysis: We systematically searched five electronic databases and included placebo-controlled RCTs in adults with MDD who received augmentation with lithium, SGAs, or T3. The primary outcome was response rate (defined as ≥50% depressive symptom reduction). Random-effects meta-analysis and trial sequential analysis (TSA) were conducted. We also performed publication-bias–adjustment analyses, including PET-PEESE and selection models. Subgroup analyses were conducted for individual SGAs. : To reappraise the efficacy and robustness of evidence for pharmacological augmentation strategies for MDD, focusing on lithium, SGAs, and T3. Findings Fifty-six RCTs were included (n=13616). SGA augmentation was associated with a higher response than placebo (k=45; reported as OR with 95% CI: 1.53; 1.42–1.65; I²=0%), and the evidence was supported by TSA. Conversely, while lithium showed benefit in conventional meta-analysis (k=17; OR 2.06; 1.30–3.27; I²=11.5%), this effect was not supported by TSA (accrued information size reached 8% of the required information size; 1.99, TSA-adjusted 95% CI 0.02–189.11) and became statistically non-significant in the PET-PEESE-adjusted and selection models. Additionally, T3 augmentation was not associated with significantly higher response than controls (k = 6; 1.19; 0.53–2.70). Among individual SGAs, only aripiprazole, quetiapine, brexpiprazole, and cariprazine demonstrated TSA-supported efficacy, whereas evidence for other SGAs was limited or inconclusive. Conclusion The certainty and robustness of evidence for lithium and T3 augmentation remained limited. Evidence for T3 was sparse and did not show a significant advantage over control, while interpretation of the lithium findings is further constrained by the fact that most trials were conducted before treatment-resistant depression was more operationally defined in contemporary research. SGAs with TSA-supported benefits (aripiprazole, quetiapine, brexpiprazole and cariprazine) may be prioritised, pending individual patient considerations. Study registration https://osf.io/27gp9

Background WHO considers mental disorders a significant disease burden among children and adolescents. However, there is a lack of population-based studies on the time trends of mental disorder diagnosis in this group. Objective To investigate changes in the incidence of clinical diagnoses of mental disorders among all Danish children and adolescents in the past 3 decades. Methods In this retrospective cohort study, we included all Danish-born individuals from 1976. Follow-up started in 1994 until first diagnosis of a mental disorder, 18th birthday, emigration from Denmark, death or end of study on 30 June 2023. Sex-specific cumulative incidences of diagnosis by age 18 were calculated in 5-year birth cohorts from 1976–1980 to 2001–2005 using the Kaplan-Meier estimator. Poisson regression was used to estimate the age-specific and sex-specific incidence rates. Findings From 1994 to 2023, a total of 193 354 children and adolescents received a mental disorder diagnosis. Over 3 decades the cumulative incidence of any mental disorder diagnosis before age 18 increased from 1.46% (95% CI 1.40% to 1.52%) to 14.56% (95% CI 14.36% to 14.76%) among females and from 1.22% (95% CI 1.16% to 1.27%) to 14.77% (95% CI 14.57% to 14.96%) among males. A lower mean age at first diagnosis accounted for an estimated 15–22% of the observed incidence in the most recent years. Conclusions This study demonstrates a large increase in mental disorder diagnoses. Observed rates were in part accounted for by decreasing age at first diagnosis. While some of the remaining increase may reflect a true rise in the underlying prevalence of mental disorders, changes in diagnostic practice and greater awareness of mental disorders are probable contributors. Clinical implications Estimates of specific diagnostic rates are essential for appropriate healthcare planning and resource allocation to accommodate the increasing number of mental disorder diagnoses among children and adolescents.

Background Older adults have the highest suicide rates globally, yet contemporary national evidence on suicide in later-life remains limited in Ireland. Objective To examine the rates, sociodemographic and clinical factors of older adults who die by suicide in Ireland. Methods Retrospective analysis of coronial files of older adults aged ≥60 years who died by suicide in Ireland during 2015–2020, with adults aged 18–59 years as a comparison group. Crude suicide rates per 100 000 were calculated. Differences in sociodemographic and clinical variables were tested using 2 or Fisher’s exact tests. ORs with 95% CIs compared suicide methods between age groups. Poisson regression models estimated changes in suicide rates. A Lived Experience group contributed to interpretation. Findings Between 2015 and 2020, 654 older adults died by suicide. The average suicide rate for older adults was 12.0 per 100 000 compared with 17.5 per 100 000 among adults aged 18–59. However, marked within-group variation existed, with older single males having the highest suicide rate overall (38.1 per 100 000). Among older adults, males aged 60–69 years had the highest rate (21.8 per 100 000). Suicide risk increased during summer, especially among older adults. Rates declined in 2020 in older males. Among individuals who died by suicide, older adults were more likely to be married, live alone and in agricultural and managerial socioeconomic groups compared with adults aged 18–59. Among suicide deaths, older adults were more likely to have physical health conditions, recent acute pain, loneliness and seen their general practitioner (GP). Within the suicide cohort, financial concerns and interpersonal difficulties were more commonly experienced by younger adults. Method profiles differed by age, with drowning and firearm-related suicides higher among older adults. Conclusions Older adults who died by suicide in Ireland had distinct sociodemographic and clinical profiles compared with younger adults. While mental health symptoms were common across age groups, later-life suicide was more frequently characterised by physical health conditions, loneliness and recent healthcare contact. Clinical implications Findings highlight the need for sex-specific and age-specific suicide prevention strategies that address systemic factors, including improved GP training and strengthened community-based services. Increased contact with healthcare services highlights opportunities for intervention.

Background People with mental disorders bear an excessive burden of oral diseases. This burden can exacerbate the personal, social and economic impacts of mental disorders. There is a need for transformational research to tackle this problem, which should start with co-setting research priorities with people with lived experience and key stakeholders. Objective This national Priority Setting Partnership (PSP) aimed to identify the top 10 research priorities for oral health among people with mental disorders. Methods Following the James Lind Alliance approach, this three-stage PSP engaged people with mental disorders, carers and staff of all levels and decision-makers from healthcare, social care and non-governmental organisations. In stage 1, questions for research were gathered via an online survey. Summary questions were then formed and checked against existing evidence. In stage 2, unanswered questions were compiled into an online shortlisting survey. In stage 3, a consensus workshop was held to determine the top 10 research priorities. Findings From 1214 questions received in stage 1, 60 unanswered questions were formed. Based on 2377 shortlisting survey responses, the 25 top-ranked questions were taken to the consensus workshop, where the top 10 research priorities were determined by 27 participants. The most important research question was ‘What are the best ways to integrate oral health within physical health checks and follow-up care for people with severe mental ill-health?’ Other questions focused on the capability of primary care, mental health and dental teams in supporting oral health, integrated system-level models of dental care and financial incentives for professionals. Discussion This PSP identified the top 10 research priorities for oral health among people with mental disorders, which would guide future research and funding aimed at reducing the stark inequalities in oral health between this group and the general population. Clinical implications Addressing the priorities identified in this consultation through transformational research would lead to impactful changes in healthcare and public health practice and policy. This in turn would address the burden of oral diseases among people with mental disorders and contribute towards improving their mental and physical health and recovery.

Background Adolescent and young adult (AYA) mothers often experience unmet psychosocial needs, and those under 25 years of age are at increased risk of perinatal depression. Although home visiting programmes may be beneficial, no controlled trial has evaluated a programme co-designed with first-time AYA mothers and grounded in their lived experiences. Objective We evaluated the effect of the co-designed Early Partnership programme on perceived fulfilment of psychosocial needs and postnatal depressive symptoms among first-time AYA mothers. Methods We emulated a target trial using data from a pragmatic historically controlled study in four Tokyo municipalities. Participants were primiparous women aged 16–25 years. The intervention group included 151 participants and the control group included 158 participants. The intervention group received intensive tailored home visits by multi-professional family support workers from pregnancy to 12 months postnatally, and the historical control group received publicly funded health and social services. Findings Retention at 12 months was high in both groups (intervention group, 82.1%; control group, 82.9%). For the primary outcome analysis, the intervention group had greater improvement in perceived fulfilment of psychosocial needs at 6 months postnatally (difference in mean changes 4.16, 95% CI 1.35 to 6.97, Cohen’s d 0.40, 95% CI 0.13 to 0.67) and 12 months postnatally (difference in mean changes 3.93, 95% CI 0.63 to 7.23, Cohen’s d 0.39, 95% CI 0.06 to 0.72) than the control group. Postnatal depressive symptoms were lower in the intervention group at 6 months postnatally (mean difference –1.54, 95% CI –2.70 to –0.38, Cohen’s d –0.34, 95% CI –0.59 to –0.08) and 12 months postnatally (mean difference –1.55, 95% CI –2.74 to –0.36, Cohen’s d –0.34, 95% CI –0.61 to –0.07). Well-being also improved at each time point, but estimates were imprecise. Conclusions The Early Partnership programme, co-designed with young mothers and delivered by multi-professional teams, was acceptable and effective in improving perceived fulfilment of psychosocial needs and postnatal depressive symptoms. Clinical implications These findings suggest that a person-centred and relationship-based home visiting model, delivered through a non-stigmatising design, may represent a plausible model of maternal care.

Background Mental health in the UK has worsened over the last 15 years, a period marked by major systemic shocks. Objective We investigated annual changes in population-level psychological distress and the impact of five systemic shocks: the referendum on European Union membership (Brexit), two COVID-19 lockdowns, Russia’s invasion of Ukraine and the UK Government’s 2022 ‘mini-budget’. Methods We used longitudinal survey data from the UK Household Longitudinal Study, including 87 857 between years 2009 and 2024. We used Bayesian time series models to evaluate annual changes in psychological distress and the association with each shock, including subgroup analyses by age group, sex, ethnicity, deprivation quintile and employment status. Outcomes We found evidence of increasing psychological distress from 2009 to 2023 (+1.085 point increase in 12-item General Health Questionnaire scores; credible interval (CrI) 0.987 to 1.184). In interrupted time series models, we observed increased psychological distress immediately after the Brexit referendum (+0.117, CrI 0.029 to 0.205) and the first COVID-19 lockdown (+0.649; CrI 0.531 to 0.767), with more insidious monthly increases in psychological distress after the Russian invasion of Ukraine (+0.010, CrI 0.004 to 0.023) and the 2022 mini-budget (+0.015, CrI 0.005 to 0.034). We found considerable sociodemographic variation by age, sex, ethnicity, deprivation and employment status. Conclusions We found that some systemic shocks had detrimental effects on population mental health in the UK, being most pronounced for the Brexit referendum and first COVID-19 lockdown. Clinical implications Our results demonstrate that population mental health can change in response to systemic shocks. This should inform the design of responsive clinical and public mental health provision.

Background France reports markedly lower adult attention-deficit/hyperactivity disorder (ADHD) medication use than other high-income countries despite similar prevalence. Methylphenidate is the predominant ADHD medication dispensed in France, accounting for the large majority of stimulant prescriptions in adults. Until recently, methylphenidate initiation was restricted to hospital specialists and largely excluded adult indications. Regulatory changes between 2021 and 2023 expanded adult access. Objective Examine national trends in adult methylphenidate dispensing in France and quantify the impact of the November 2021 regulatory reform. Methods Nationwide retrospective cohort study using the French National Health Data System (SNDS), including adults (≥18 years) with at least one community pharmacy dispensation of methylphenidate between January 2015 and December 2024. Weekly population-standardised dispensing rates were analysed using interrupted time-series models (quasi-Poisson) to estimate level and trend changes, stratified by sex and prescriber specialty. A secondary analysis examined incident treatment initiation to distinguish new users from individuals continuing pre-existing therapy. Findings Between 2015 and 2024, a total of 195 393 adults received methylphenidate. Before the reform, weekly dispensing grew gradually (~0.2% per week). At reform implementation, an immediate 10.9% level increase occurred, followed by a sustained acceleration (~0.7% per week), largely driven by new treatment initiations. Similar patterns were seen in both sexes, though the immediate increase was greater for dispensing attributed to psychiatrists. Conclusions The November 2021 reform was associated with a rapid and sustained expansion of adult methylphenidate use over the 3 years following the reform, primarily through increased treatment initiation, suggesting that prior regulatory constraints largely explained historically low treatment rates. Longer follow-up will be needed to assess whether this trajectory is maintained. Clinical implications Regulatory changes expanding ADHD treatment access may produce rapid prescribing increases, requiring adequate specialist capacity and stimulant use monitoring.

Background Lithium has long been considered to reduce suicidal behaviour in patients with affective disorders, but evidence from large real-world populations remains limited. Objective To estimate the effects of lithium initiation and continuation on suicide deaths and non-lethal suicidal behaviours among adults with bipolar disorder or major depressive disorder. Methods We emulated two target trials using electronic health records and administrative claims from US veterans between January 2010 and December 2022. The first trial benchmarked results against the CSP-590 randomised trial by estimating the 1-year risk of suicide-related events (non-fatal suicide attempts, hospitalisations to prevent suicide or suicide deaths) among patients with a recent suicide attempt initiating lithium versus not initiating lithium. The second trial extended follow-up to 10 years to estimate risks of suicide deaths and non-lethal suicidal behaviours separately, including subgroup analyses by age and diagnosis. An additional analysis removed the requirement of a prior suicide attempt. Findings In the benchmarking analysis, the 1-year risk ratio for suicide-related events comparing lithium initiation with no initiation was 1.06 (95% CI 1.01 to 1.12), consistent with findings from the CSP-590 trial. In the extended analysis, the 10-year per-protocol risk ratio for suicide death was 1.00 (95% CI 0.86 to 1.15) and for non-lethal suicidal behaviours was 0.96 (95% CI 0.90 to 1.02). Results were similar among individuals with and without a prior suicide attempt. Conclusion When added to ongoing pharmacological treatment for patients with affective disorders, lithium may not substantially reduce suicide risk highlighting the need for additional suicide prevention strategies in this population. Limitations include lack of information on adherence, dosage or blood levels of lithium which may have obscured existing differences. Clinical implications Our findings suggest that adding lithium therapy to the ongoing treatment regimens of patients with affective disorders for the sole purpose of reducing suicide may not be well-tolerated or meaningfully reduce suicide risk.

Background Understanding how multiple long-term conditions (MLTCs) develop and cluster across the life-course remains a key public health priority. Evidence on how these patterns relate to patient-centred outcomes among patients with mental health disorders remains limited. Objective To evaluate patient-centred outcomes in patients with a history of depression and MLTC. Methods A retrospective matched cohort study design was implemented in the Clinical Practice Research Datalink, a UK primary care database. Patients aged ≥10 years with a first recorded diagnosis of depression between 1 January 2003 and 31 December 2023 were matched (1:1) to a comparator without a depression history on age, sex and practice. MLTC was defined using 256 long-term conditions. Clusters of MLTC were derived for each life decade via multiple correspondence analysis and k-means clustering. Patient-centred burden was assessed across eight patient-prioritised ‘work themes’: symptoms, emotions, investigation and monitoring, health service and administration, learning and adapting, medication, finance and accumulation and complexity. Poisson and logistic regression models assessed associations between decade-specific MLTC clusters and burden indicators. Findings Among 1 962 757 patients with incident depression, 1 563 065 (78%) presented with MLTC over a mean follow-up of 14 years (SD=6), compared with 987 138 (50%) of comparators (mean follow-up=10, SD=7). Patients with depression history had a higher median number of LTCs (5 (IQR 3–9) vs 4 (3–8)). Clusters of MLTCs varied by life decade: atopic triad and liver clusters predominated in early life, metabolic and cardiovascular (CVD) clusters in midlife and musculoskeletal (MSK) and respiratory in later life. The burden patterning varied between cases and their comparators, who showed lower overall burden and distinct early-life patterns. The strongest prognostic cluster for increased burden in patients with depression changed across life. In early life, the metabolic cluster had the highest risk (incidence rate ratio=1.02 (95% CI 1.01 to 1.03)), followed by respiratory and CVD during midlife and MSK/functional in later life. Conclusions MLTC in patients with depression is common, shows dynamic temporal patterning and leads to high patient-centred burden from adolescence onwards. Clinical implications The study identified specific burdensome clusters of MLTC at each life decade which could inform MLTC prevention for patients with depression.

Background Minoritised ethnic families in England experience disproportionate barriers to accessing neurodevelopmental disorder (NDD) assessment and support despite universal healthcare provision. Existing evidence has focused on caregivers’ perspectives or non-UK settings but little is known about how healthcare professionals (HCPs) perceive and interpret these inequities. Addressing this gap is essential for improving access, service design and workforce development. Objective To explore HCPs’ perceptions of the barriers and facilitators influencing minoritised ethnic families’ access to NDD services in England. Methods A multiple methods design was used, comprising an online national survey (n=264) and two online focus groups with primary, secondary and allied health professionals (n=9). Survey data were summarised descriptively and free text responses analysed using summative content analysis. Focus group transcripts underwent reflexive thematic analysis. Findings were summarised following parallel analysis of each data set. Patient and public involvement and engagement members from minoritised ethnic backgrounds contributed throughout. Findings HCPs identified four interconnected barriers they perceived to influence access for minoritised ethnic families: (1) language, communication and meaning-making challenges, including differences in how concepts and expressions are understood, inconsistent interpretation and limited mental health literacy; (2) difficulties navigating complex, fragmented NDD pathways, exacerbated by digital literacy demands and unclear referral routes; (3) limited caregiver knowledge and understanding of NDDs, affecting symptom recognition and the ability to advocate effectively and (4) cultural norms, beliefs and stigma, including preferences for non-Western models of care, fear of diagnostic labels and the influence of extended family. Professionals also highlighted the impact of unconscious bias and limited cultural representation within services on referral decision-making and caregiver engagement. HCPs described several effective strategies for mitigating these barriers, such as culturally attuned communication, community-based engagement and flexible assessment approaches. Conclusions Inequitable access to NDD services arises from the interaction of cultural, relational and structural factors across the healthcare pathway. HCPs’ insights reveal multiple entry points for improving equity, particularly through communication support, culturally responsive practice and simplified referral processes. Clinical implications Embedding culturally informed communication, improving caregiver education, strengthening workforce diversity and coproducing service changes with communities may reduce avoidable delays and promote equitable access to neurodevelopmental assessment and support.

Background Young peoples’ mental health is worsening, increasing demands on Child and Adolescent Mental Health Services (CAMHS) crisis teams. However, evidence is lacking regarding the effectiveness of such services. To pave the way for service developments and robust evaluation, it is crucial to establish a consensus on the core competencies for CAMHS crisis clinicians and the most desirable outcomes from their input. Objective To elicit and establish consensus among experts, including those with relevant lived experience, regarding the most important staff competencies and outcomes in this service context. Methods A three-round Delphi study was conducted with young people (aged 18–25 years with relevant lived experience of CAMHS crisis team input), parents/carers and mental health clinicians/academics. The study aimed to establish consensus (≥70% agreement) on which core staff competencies and outcomes were perceived as ‘essential’/‘very important’ in relation to CAMHS crisis services. Findings Of 69 initial participants, 43 (62%, mainly young people) completed all three rounds. A broad consensus was reached, with over 90% of proposed items meeting the consensus threshold. The strongest agreement was found for competencies in the therapeutic alliance domain, particularly cultural competency (93%) and validation (91%). For the case formulation domain, a holistic mental state examination (91%) was highly prioritised. Key outcomes with high consensus included improved communication with support networks (91%), better understanding of the young person (88%), feeling validated (88%) and reduced involuntary inpatient admissions (88%). The findings were integrated into a Theory of Change-based logic model illustrating how these skills and knowledge could lead to the desired outcomes. Conclusions Our results demonstrate a clear stakeholder consensus prioritising relational, validating and personalised approaches to assessment and intervention over an emphasis on administrative or diagnostic processes in CAMHS crisis care. The findings also highlight a desire to move from a perception of a paternalistic risk management style to collaborative, community-based support. Clinical implications These findings underscore the need for crisis team clinicians to be trained and supported to deliver care that is relationship-based, trauma-informed and culturally responsive. These should potentially translate into better outcomes for young people, their families and the crisis team workforce itself.

Background Post-psychosis weight gain is commonly rapid, yet prediagnosis weight changes are under-researched. The untreated phase of first-episode psychosis (FEP) can be characterised by behaviour which could lead to weight loss, triggering physiological adaptations which prime the body to regain weight. Objective We aimed to investigate the prevalence and extent of weight loss prior to diagnosis of FEP, and to investigate its impact on subsequent weight gain. Methods We used Clinical Practice Research Datalink primary care data, supplemented with linked hospital episode statistics, ethnicity and deprivation data to estimate pre-FEP weight loss prevalence. We then used multiple linear regression to assess its association with subsequent weight change, while adjusting for relevant confounders. Findings Primary analysis included 369 individuals with adequate data. 53% of individuals experienced weight loss before FEP. Using percentage weight change as an outcome, individuals with pre-FEP weight loss gained weight post-FEP at over twice the rate of those without prior loss (8.93% (95% CI 6.90% to 10.96%) bodyweight per year vs 4.07% per year (95% CI 1.90% to 6.24%); p=0.005). Each 1% of pre-FEP weight loss predicted 0.41% (95% CI 0.23% to 0.59%) additional annual weight gain (p=0.004), most pronounced within 6 months and independent of antipsychotic treatment selection. Using kilogram per year as an outcome, average gain (6.49 kg (95% CI 5.28 kg to 7.70 kg)) exceeded average prior loss (4.83 kg (95% CI 4.00 kg to 5.66 kg)) by 1 year. Findings were robust across sensitivity analyses. Conclusions Pre-FEP weight loss is common and predicts rapid post-diagnosis gain. While all patients were expected to gain weight, those with pre-FEP weight loss gained double the weight of those who had not lost weight. Clinical implications Clinicians treating individuals with FEP should enquire about weight loss in the pretreatment period, which predicts extra weight gain in the initial period following diagnosis. This could inform early intervention to avoid consequences of short-term weight gain.

Background Somatic and psychiatric illnesses and multimorbidities increase stress-vulnerability and decrease well-being. Objective We aimed to identify high-risk disorder profiles for lower well-being and well-being decline under stress, modelling COVID-19 as a natural experiment. Methods The global Collaborative Outcomes Study on Health and Functioning during Infection Times survey assessed the World Health Organization-Five Well-being Index (WHO-5) (0–100) retrospectively pre-pandemic and intra-pandemically. Mixed-effects models, controlling for demographic/pandemic-related covariates, examined coprimary outcomes: total pre-pandemic WHO-5 and pre-to-intra-pandemic change (estimating β); pre-pandemic WHO-5 <50, new pre-to-intra-pandemic WHO-5 <50 and WHO-5 decrease ≥10 (estimating ORs±95% CIs). Fixed effects were self-reported somatic and psychiatric diagnoses and within-and-across multimorbidities. Findings Altogether, 121 066 adults (female=64.0%, white=69.0%, age=42.0±15.9 years, countries=155) with illnesses (any=49.8%/somatic=44.8%/psychiatric=16.3%) and multimorbidities (any=32.8%/somatic=27.3%/psychiatric=7.4%/somatic-psychiatric=10.8%) were analysed. Well-being was 2–3-fold worse with psychiatric disorders (pre-pandemic: autism-spectrum disorder (β=–7.00±2.93/OR=1.27–2.65), schizophrenia/schizoaffective disorder (β=–5.39±3.42/OR=1.09–2.64); pre-to-intra-pandemic: major depressive disorder (β=–2.45±0.89/OR=1.25–1.55), post-traumatic stress disorder (β=–1.98±1.42/OR=1.19–1.67)) versus somatic disorders (pre-pandemic: diarrhoea (β=–3.29±2.49/OR=1.11–2.15), chronic skin disease (CSD) (β=–2.53±1.44/OR=1.11–1.65); pre-to-intra-pandemic: CSD (β=–2.31±1.47/OR=1.23–1.75), injury (β=–2.22±0.99/OR=1.11–1.40)). Multimorbidities were associated with non-linear/supra-additive adverse outcomes beyond single disorders (pre-pandemic: anorexia nervosa+schizophrenia/schizoaffective disorder (β=–27.58±12.71/OR=1.41–19.94), inflammatory bowel disease+psychosis (β=–24.89±10.59/OR=2.68–24.25), stroke+osteoarthritis (β=–13.68±7.33/OR=1.23–6.48); pre-to-intra-pandemic: haemorrhoids+obsessive-compulsive disorder (β=–8.86±6.54/OR=1.22–5.21), binge-eating disorder/bulimia nervosa+social anxiety disorder (β=–6.87±5.49/OR=0.78–2.85), back pain+retinopathy (β=–6.55±6.54/OR=1.04–4.69)). Dose–response relationships were observed between the number of disorders and poorer well-being (pre-pandemic per diagnosis: psychiatric (β=–1.22±0.23/OR=1.11–1.17), somatic (β=–0.21±0.13/OR=1.02–1.05); pre-to-intra-pandemic per diagnosis: psychiatric (β=–0.37±0.24/OR=1.04–1.10)). Conclusions Poor well-being and further decline under stress were observed particularly with psychiatric illnesses and complex psychiatric and mixed psychiatric-somatic multimorbidity. Clinical implications The finding of supra-additive multimorbidity burden highlights a need for targeted care models, beyond individual conditions. Vulnerable groups require support during crises, beyond COVID-19.

Background Stress-related mental ill health is highly prevalent, and most individuals first seek help in primary care where access to psychological support is often limited. Objective To test whether nurse-led collaborative care (CC) is non-inferior to cognitive behavioural therapy delivered as psychologist-guided self-help (GSH-CBT) in reducing stress for adult primary care patients with stress-related mental ill health. Methods A randomised controlled non-inferiority trial where 172 adult primary care patients with mild to moderate stress-related mental ill health were allocated to nurse-led CC or GSH-CBT (1:1). The primary outcome was the Perceived Stress Scale-10 administered every 3 weeks during the 12-week treatment phase. The a priori non-inferiority margin was 0.3 d, requiring the one-sided 95% CI of the effect size to fall within this bound. Secondary outcomes were symptoms of exhaustion, sleep problems, depressive symptoms, general anxiety and quality of life. Findings In both conditions, participants showed large, significant within-group improvements on the primary outcome and all secondary outcomes. The primary outcome showed a small between-group difference (d=0.22), favouring GSH-CBT, with the CI upper bound (0.52) exceeding the non-inferiority margin. For secondary outcomes, GSH-CBT led to a greater reduction in exhaustion (d=0.28; 95% CI 0.64 to 0.002). No other between-group differences were observed. Conclusions Nurse-led CC was not non-inferior to GSH-CBT. Effect differences were small, but improvements were slightly larger in GSH-CBT. Clinical implications Given that nurse-led CC is safe, easy to administer, and that significant within-group improvements were observed across all measures, this intervention could be a viable option in primary care settings where psychologist-delivered treatment is limited.

Background Conflicting evidence from observational studies and randomised trials has created uncertainty about the association between attention-deficit/hyperactivity disorder (ADHD) medication use and self-harm. Objective To assess the risk of incident self-harm associated with use of ADHD medication across multiple healthcare systems. Methods We conducted a multinational self-controlled case series study using a common data modelling approach to assess the risk of self-harm among individuals treated with ADHD medication across population-based databases from Hong Kong, New Zealand, South Korea, Taiwan and the United Kingdom. We included individuals who initiated ADHD medication and had a record of self-harm between 2001–2020. Incidence rate ratios (IRRs) for self-harm were calculated using conditional Poisson regression, comparing three risk periods of ADHD medication exposure (ie, the 90 days before medication initiation, the first 90 days of medication use and the subsequent treatment period) to non-exposure periods. Adjusted IRRs and 95% CIs were estimated for various risk periods. Estimates from each site were pooled using a random-effects model. Findings A total of 461 024 individuals with at least one prescription for ADHD medication were included, of whom 6847 had an incident self-harm event during the observation period. The risk was highest during the 90 days before medication initiation (pooled adjusted IRR: 2.58; 95% CI 2.12 to 3.13), followed by the first 90 days of medication use (pooled adjusted IRR: 1.78; 95% CI 1.23 to 2.57), and lowest in the subsequent treatment period (pooled adjusted IRR: 1.27; 95% CI 1.01 to 1.60). Results were consistent across included databases. Conclusions While the use of ADHD medication was associated with self-harm, the highest risk occurred during the unexposed period immediately before starting treatment. The consistent findings across various health systems do not support ADHD medications as the main driver of self-harm. Instead, the increased risk observed prior to treatment may be related to untreated ADHD features. Clinical implications Although our findings provide reassurance that ADHD medications do not appear to be the main driver of the increased self-harm risk, the persistently elevated risk highlights the need for ongoing clinical monitoring and counselling before and during treatment.

Background Cognitive deficits across psychiatric disorders are common and difficult to treat. Semaglutide, a GLP-1 receptor agonist, shows potential cognitive benefits in diabetes and obesity, but effects in psychiatric populations remain unclear. Objective To determine whether initiation of semaglutide is associated with fewer cognitive signs/symptoms over 12 months among adults with psychiatric disorders. Methods Retrospective cohort study using de-identified multicentre US electronic health records (EHRs) in NeuroBlu Data spanning 1999–2024. We included adults with any International Classification of Diseases (ICD)-9/-10 psychiatric diagnosis with at least one semistructured, clinician-rated routine cognitive assessment in the 12 months before and at least one in the 12 months after initiating an antidiabetic drug. Semaglutide initiation was compared against four comparator strategies including sitagliptin, empagliflozin, glipizide or no antidiabetic treatment. Primary outcome was a 0–100 composite cognitive score (0, no signs/symptoms recorded; 100, signs/symptoms present across all domains) derived from semistructured, clinician-rated routine cognitive assessments across memory, attention, orientation and other cognitive functions, with a 12-month follow-up after antidiabetic drug initiation. We estimated mean ratios (MR) and 95% CIs between comparisons with the parametric g-formula, adjusting for baseline cognitive score and prespecified covariates. Additional analyses were conducted for individual cognitive domains and also grouped by major depression, psychosis and bipolar disorder. Findings Among 13 007 individuals (mean (SD) age, 62.0 (13.4) years; 6300 (48.4%) female), 1261 initiated semaglutide. Across psychiatric disorders, mean cognitive signs/symptoms scores over 12 months were lower with semaglutide (11.14) than with no treatment (14.91; MR, 0.75 (0.65–0.85); Bonferroni-corrected p=0.00002), glipizide (13.46; MR 0.83 (0.70–0.93); p=0.041) or empagliflozin (13.69; MR, 0.81 (0.69–0.94); p=0.016) and lower but not significantly different from sitagliptin (12.52; MR, 0.89 (0.77–1.02); p=0.50). Associations were stronger for memory and broader cognitive functions. Similar effect sizes were seen across disorders but were only consistently significant in major depression. Conclusions In this EHR-based cohort of adults with psychiatric disorders, semaglutide initiation was associated with lower clinician-recorded cognitive signs/symptoms than several comparators over 12 months. Clinical implications Randomised clinical trials are needed to confirm causality and clinical utility of semaglutide to reduce cognitive signs/symptoms in psychiatric disorders.

Background Literature guiding the use of long-acting injectable antipsychotics (LAIAs) versus oral antipsychotics (OAs) in people with intellectual disability (PWID) remains scarce. Objective Examining the associations of LAIAs vs OAs with healthcare utilisation among PWID. Methods This self-controlled case series study used electronic health records from Hong Kong. We included adults with intellectual disability prescribed both LAIAs and OAs at different periods in 2004–2023. We compared within-individual LAIA and OA periods, adjusting for age, calendar year, season, inpatient stay and concomitant psychotropic use, using conditional Poisson regression to estimate incidence rate ratios (IRRs) for all-cause emergency department (ED) visits; all-cause hospitalisations; hospitalisations for psychiatric disorders, schizophrenia/bipolar disorder, behaviour-related problems, somatic disorders and cardiovascular diseases (CVDs) and diagnosis records of extrapyramidal symptoms (EPS); falls and fractures. Subgroup analyses were conducted by diagnosis of schizophrenia or bipolar disorder. Findings We identified 1675 PWID who had been prescribed both OAs and LAIAs at different periods during the study period. LAIA use was associated with lower risks of incident all-cause ED visits (adjusted IRR: 0.71, 95% CI 0.51 to 0.98), all-cause hospitalisations (0.91, 0.85–0.98); hospitalisations for psychiatric disorders (0.90, 0.81–0.99); for schizophrenia/bipolar disorder (0.86, 0.75–0.99) and EPS (0.34, 0.23–0.51), compared with OAs. In PWID with schizophrenia/bipolar disorder, LAIAs were associated with lower risks of all-cause hospitalisations, hospitalisations for psychiatric disorders, schizophrenia/bipolar disorder, behaviour-related problems and somatic disorders, and EPS, but a higher risk of hospitalisations for CVDs (with hypertensive disease being the most common), compared with OAs. In contrast, among PWID without such diagnoses, LAIA use was associated with higher risks of all-cause hospitalisations, hospitalisations for somatic disorders; a lower risk of incident all-cause ED visits and hospitalisations for CVDs, but no significant difference in hospitalisations for behaviour-related problems, compared with OAs. Conclusions These findings are consistent with potential benefit of LAIAs among PWID with schizophrenia or bipolar disorder, while raising concern about off-label use in those without these diagnoses. Clinical implications LAIAs may be considered in PWID with schizophrenia or bipolar disorder; off-label use in those without these diagnoses should be approached cautiously, and deprescribing may be considered where appropriate if these results are replicated.

Background The Psychosis Polyrisk Score (PPS) was developed to characterise exposure to environmental and developmental risk factors for psychosis. In previous studies, the PPS showed promise particularly in discriminating between individuals at clinical high risk for psychosis (CHR-P) and community controls (CC). Objectives This study aimed to (1) perform an external validation of the PPS model in a large independent sample and (2) refine the model using expanded predictor data. Methods Participants were recruited through the AMP SCZ program: n=1642 CHR-P, n=519 CC. We performed a formal external validation of the PPS original model. The model was then refined incorporating expanded predictor data (perceived loneliness, neighbourhood quality) and increasing the granularity of existing predictors (ethnicity, childhood trauma, parental severe mental illness). Next, we evaluated the refined model through repeated nested cross-validation and compared it to the original model retrained in the new dataset. Discrimination (Harrell’s C-index) and calibration (intercept and slope) were used to assess model performance. Findings The externally validated PPS original model showed good discrimination (C=0.777, 95% CI 0.756 to 0.797) between CHR-P and CC and good calibration (intercept=0; slope=1.003) after recalibration. The refined PPS model exhibited higher internally cross-validated discrimination than the retrained original model (C=0.876, 95% CI 0.860 to 0.891 vs C=0.796, 95% CI 0.775 to 0.816), as well as good calibration performance (intercept=–0.008; slope=1.031). Conclusions The PPS showed good generalisability to a large, independent sample, and performance improved after model refinement. Clinical implications The PPS represents a potential scalable tool within stepped assessment frameworks for identifying individuals who warrant further CHR-P assessment. Trial registration number NCT05905003.

Anhedonia, broadly defined as a reduced ability to experience interest or pleasure, represents an important transdiagnostic neuropsychiatric symptom dimension which may benefit from targeted diagnostics and treatments. Different lines of research have proposed that it comprises multiple facets, including deficits in anticipatory (‘wanting’) and consummatory (‘liking’) reward processing as well as reward learning and affects different aspects of life (eg, social, physical, cognitive). Certain facets—more specifically anticipation, motivation and reward learning—likely involve blunted phasic dopaminergic signalling. However, recent meta-analytical evidence of human depression studies indicates that prodopaminergic antidepressants produce relatively small improvements in anhedonia symptoms and suggest that mechanisms beyond dopamine likely contribute to anhedonia. This stimulated an expert meeting to review the literature and define priorities for future research in anhedonia. A central key priority is developing a translational biologically-informed nomenclature and consensus that solves the current mismatch between constructs, paradigms and measures, and mechanisms, which separates discrete reward-related processes such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure. Clinical research priorities are improved multimodal measurement tools, integrating neurobiological frameworks (eg, neuroimaging, electrophysiology and liquid biomarkers capturing dopaminergic, glutamatergic, opioid and immunometabolic pathways) and transdiagnostic studies across neuropsychiatric disorders and developmental stages. Innovative trial designs that explicitly target anhedonic phenotypes as a primary outcome and test mechanism-based interventions are also needed. Translational research recommendations include back-translation strategies that begin with patient-relevant phenotypes followed by the development of comparable human and animal tasks that target reward-related processes, such as effort allocation, reward learning and anticipatory interest versus consummatory pleasure, improve cross-species behavioural paradigms and enhance methodological rigour and reproducibility. Collectively, these recommendations will help refine the conceptualisation of anhedonia and advance its role within precision psychiatry as a mechanistically grounded target across multiple disorders.

Background Solitary confinement is extensively used in prisons, constituting a risk of deteriorating health. However, its associations with mental health disorders remain unclear. Objective To investigate the association between history of diagnosed mental health disorders and solitary confinement among incarcerated individuals. Methods We included 35210 individuals with 51502 incarcerations in Norway from 2015 to 2022 in the Norwegian Prison Release study (nPRIS), linking national prison, health, mortality and demographic registries. Mental health disorders diagnosed within 5 years before incarceration were identified. The primary outcome was solitary confinement and four subtypes: court decided, disciplinary, self-requested and security cell. By analysing all incarcerations, we estimated adjusted ORs (aORs) and rate ratios (RRs) with logistic and negative binomial regression, using robust SEs to account for individual-level clustering across multiple incarcerations. Findings Among all individuals with a 5-year history of diagnosed mental health disorders (n=18 315), 30.8% experienced solitary confinement, compared with 21.3% among those without a diagnosis (n=16 895). Mental health disorders were associated with higher odds of any solitary confinement (aOR 1.77, 95% CI 1.68 to 1.85) and security cell placement (aOR 4.28, 95% CI 3.57 to 5.13). People with mental health disorders also had a higher rate of disciplinary (adjusted rate ratio (aRR) 3.84, 95% CI 3.41 to 4.33) and self-requested (aRR 2.46, 95% CI 1.91 to 3.18) solitary confinement days. Substance use disorders, severe mental illness and multimorbidity were associated with a higher rate of solitary confinement days, while mental health disorders were inversely associated with court decided solitary confinement (aOR 0.52, 95% CI 0.47 to 0.57; aRR 0.48, 95% CI 0.41 to 0.57). Conclusion People with a history of diagnosed mental health disorders disproportionately experience solitary confinement in prison, risking further deterioration of health. Clinical implications Health authorities and correctional services should reduce solitary confinement and develop alternative, health-protective segregation strategies for people with mental health disorders.

Background Differentiating bipolar disorder (BD) from major depressive disorder (MDD) during major depressive episodes remains a significant challenge. EDIT-B is an in vitro diagnostic test based on machine learning (ML) method integrating clinical metadata with adenosine-to-inosine (A-to-I) RNA editing signatures in eight genes (GAB2, IFNAR1, IL17RA, LYN, MDM2, PRKCB, PTPRC, ZNF267) to differentiate BD from MDD. Objective The objective of this study is to assess and confirm the diagnostic performance of EDIT-B in a new, independent, double-blind, external, multicentre European cohort. Methods We evaluated EDIT-B results across four European centres (Spain, France, Denmark) compared with physician diagnoses. Explainability and sensitivity analyses were performed to identify the primary drivers of the model. Findings In 393 patients with current major depressive episode (238 MDD; 155 BD), EDIT-B demonstrated robust performance: area under the curve-receiver operating characteristic of 0.873 (95% CI 0.837 to 0.909), sensitivity of 82.6% (95% CI 75.7% to 88.2%) and specificity of 80.3% (95% CI 74.6% to 85.1%). Performances were consistent across sites and all stratified patient subgroups, corroborating previous results. Explainability analysis pointed to RNA editing biomarkers as the most important variables for EDIT-B diagnosis. Conclusion This study confirms the diagnostic performances of EDIT-B showing that A-to-I RNA editing coupled with ML methods is a reliable approach to distinguish BD from MDD. Clinical implications EDIT-B represents an innovative, reliable and complementary diagnostic tool supporting psychiatric practice and enhancing clinical outcomes with potential impact in reducing diagnostic delays, tailoring the therapeutic strategy and improving therapeutic alliances. These findings may represent a significant advance towards precision psychiatry, with potential to reduce misdiagnosis and inappropriate treatment. Trial registration number NCT05603819.

Background Evidence on the association between age and the long-term course of affective disorders remains mixed. Objective This study examined the 6-year symptom and diagnostic trajectories of depression and anxiety in relation to age, and assessed whether social, lifestyle, somatic and clinical factors explained observed age-related differences. Methods A cohort of 1701 participants aged 18–65 years with a current depressive and/or anxiety disorder from the Netherlands Study of Depression and Anxiety were assessed biennially over 6 years. Clinical diagnoses were ascertained using the Composite International Diagnostic Interview, while symptom severities were measured with the Inventory of Depressive Symptomatology, Beck Anxiety Inventory, Fear Questionnaire and Penn State Worry Questionnaire. Linear mixed-effects models examined age differences in symptom changes over time; multinomial logistic regression examined age differences in diagnostic course. Models were sequentially adjusted for social, lifestyle, somatic and clinical factors to explain observed age-related differences. Findings Over the 6-year follow-up, older age was associated with slower improvement in depressive (bper 10 years=0.191 (0.103 to 0.279)) and anxiety symptoms (bper 10 years=0.119 (0.048 to 0.191)), but not for fear or worry. Older age was associated with a higher likelihood of a chronic course versus early remission (RRRper 10 years=1.19 (1.05 to 1.36)), primarily driven by depression chronicity. Age-related differences in symptom trajectories persisted across all adjusted models, while associations with depression diagnostic chronicity were attenuated after adjustment for social and lifestyle factors. Conclusions Higher chronological age is an independent risk factor for a less favourable long-term course of affective disorders, particularly depression, characterised by slower symptom improvement and increased chronicity. Clinical implications Age-tailored depression management, including closer follow-up and timely treatment optimisation, may help improve clinical course in later life.

Background Attention-deficit/hyperactivity disorder (ADHD) medications can reduce ADHD symptom severity in individuals with comorbid autism spectrum disorder (ASD). However, clinical guidance on pharmacological treatment of ADHD in this clinical population remains limited and inconsistent. Characterising real-world treatment patterns (ie, initiation timing, medication choices, switching, discontinuation) and the impact of alternative medication choices on clinical outcomes is critical for informing evidence-based management strategies. Objective To (1) characterise ADHD pharmacological treatment patterns in youth with ADHD+ASD versus ADHD alone and (2) assess whether using alternative ADHD medications versus methylphenidate is associated with differential changes in negative clinical outcomes among youth with ADHD+ASD. Methods This is a population-based cohort study using Swedish national registers. The study included children (<13 years) and adolescents (13–17 years) with an incident ADHD diagnosis between 2007 and 2018 and followed-up until 2021, comparing youth with co-occurring ASD (n=24 117) and ADHD alone (n=79 830). Descriptive outcomes included time to pharmacological treatment initiation, medication type, number of medication switches and discontinuations. The primary outcome was changes in rates of inpatient psychiatric hospitalisations, accidental injuries and specialist care visits for substance use, depressive or anxiety disorders in the 1 year after versus the 1 year before medication initiation. Findings Individuals with ADHD+ASD experienced longer delays to treatment initiation (12–14% initiated >12 months after diagnosis vs 7–8% in ADHD alone). Children with ADHD+ASD were slightly more likely to discontinue treatment within 3 months (16% vs 12%) and had the highest average number of medication switches within 3 years (2.6; IQR 0.0–2.0). In within-individual analyses, comparisons of alternative ADHD medications versus methylphenidate did not yield statistically significant differences after correcting for multiple comparisons. Conclusions Children with ADHD+ASD experienced longer delays to treatment initiation and more frequent medication switching compared with those with ADHD only. The effects of alternative ADHD medication options on key negative clinical outcomes appeared similar to those of methylphenidate. Clinical implications These findings suggest that, rather than recommending fixed first-line and second-line treatments for individuals with ADHD-ASD, clinical guidelines should emphasise appropriate training as well as prompt and individualised treatment based on a shared decision-making process.

Medical artificial intelligence (AI) benchmarks are increasingly used to assess the readiness of large language models for health-related tasks, but aggregate performance scores can obscure clinically meaningful variation across domains. HealthBench, an open benchmark of 5000 multi-turn health conversations, represents a salient example: the score is difficult to interpret for decisions about specific clinical use cases, including those with mental health needs. Conversations involving suicidality, psychosis, eating disorders, trauma or relational dependence require recognising ambiguous disclosures, responding safely under uncertainty, avoiding reinforcement of harmful beliefs or over-reliance and knowing when to escalate to human-based crisis support. We propose that HealthBench and similar benchmarks report domain-specific results. To demonstrate feasibility and utility, we adopted OpenAI’s classified dataset to identify 332 mental health conversations, validated against human review (sensitivity 0.980, specificity 1.000, positive predictive value 1.000, negative predictive value 0.980, F1 0.990, inter-rater agreement 99.0%). We analysed mental health domain performance separately from overall HealthBench performance using a stratified random sample of 500 conversations. Across deployments, mental health point estimates differed from overall estimates by –0.034 to +0.047. Mental health domain composition was also uneven: for example, postpartum depression represented 26.8% of mental health conversations compared with 4.5% for suicidal crisis, 0.9% for psychosis and 1.5% for eating disorders. The findings suggest benchmark averages can mask domain-specific insights relevant to clinical safety. We argue that interpretable medical AI evaluation requires transparent domain composition; subgroup and failure mode reporting; calibration against clinically meaningful anchors, including human expert performance; and reproducible versioned analyses as models, grader systems and deployment contexts evolve.

Co-production is increasingly recognised as central to improving the quality, relevance and ethical integrity of mental health science, yet evidence is still needed on how lived experience involvement can be meaningfully embedded and sustained in complex research settings. Global Alliance for Living Evidence on Anxiety, Depression and Psychosis (GALENOS) is a Wellcome-funded collaboration conducting living systematic reviews and evidence triangulation, with people with lived experience contributing as Experiential Advisors and through a Global Lived Experience Advisory Board. This perspective uses GALENOS as a case example to reflect on what meaningful co-production practically requires especially in the context of large-scale, technical and international collaborations. It draws on a collective reflection designed and led by people with lived experience, developed through workshops and written contributions involving lived experience contributors, researchers and project-support staff. Discussions were organised around lived experience involvement, capacity development, diversity and representation and influence in strategic decision-making. Across these areas, contributors identified that experiential knowledge needs to become consequential, participation must be supported through care and flexibility, diversity must shape interpretation rather than representation alone and influence must be embedded in governance and decision-making. GALENOS shows that co-production is not a fixed method but an evolving relational practice requiring practical infrastructures for accessibility, accountability, continuity and ethical care.

Background Compulsive sexual behaviour disorder (CSBD), characterised by preoccupation with and loss of control over sexual behaviours, is associated with negative consequences in several areas of life. Evidence for pharmacological treatment remains limited, with only two previous randomised controlled trials and no studies comparing fluoxetine and naltrexone. Objective To investigate whether naltrexone was more efficient and tolerable than fluoxetine in the treatment of CSBD. Methods In this open-label superiority trial, 80 participants diagnosed with CSBD according to International Classification of Diseases-11 criteria were randomly assigned (1:1) to receive fluoxetine (starting dose 20 mg/day) or naltrexone (starting dose 25 mg/day) for 8 weeks followed by 6 weeks without treatment. Symptom severity was recurringly assessed using the Hypersexual Disorder: Current Assessment Scale (HD:CAS). Linear mixed models were used for intention-to-treat and per-protocol analyses of treatment effects. Findings 79 men and 1 woman were randomised to receive fluoxetine (n=40) or naltrexone (n=40). Analysis showed no statistically significant difference in HD:CAS score reduction between treatments at primary endpoint; naltrexone was not superior to fluoxetine. However, participants in the two treatment groups showed different patterns of symptom improvement over time. Two participants (5.1%) receiving fluoxetine were withdrawn due to adverse events (urticaria and elevated liver enzymes) and four participants (10.3%) discontinued treatment; six participants (15%) receiving naltrexone discontinued treatment. Conclusions Although no statistically significant between-group difference was observed at week 8, symptom trajectories and adverse effect profiles differed between groups. Clinical implications Symptom-change patterns and adverse effect profiles may guide individualised treatment decisions.

Early psychosis services, including early intervention in psychosis programmes (EIP), are built on principles of timely access, continuity and recovery-oriented, evidence-based care. While these elements are well described at a model level, less attention has been paid to the relational work required to deliver them effectively. In this perspective paper, we argue that EIP care is fundamentally relational, characterised by sustained engagement, tolerance of uncertainty and the nurturing of hope. We describe key features of this work. These include entering the person’s world, holding multiple perspectives and navigating differing explanatory models of illness, as well as the role of stigma in shaping help-seeking and engagement. We also explore the emotional and organisational tensions inherent in relationally flexible care. These include risks relating to burnout, boundaries and resource allocation. Finally, we argue that protecting relational capacity within teams through adequate resourcing, supervision and manageable caseloads may itself represent a fidelity issue for EIP systems. As EIP services expand, maintaining ‘relational fidelity’ while allowing flexibility in delivery poses a critical challenge for systems and leaders. Relational fidelity refers to preserving the conditions that allow sustained, trusting engagement and continuity over time.

Barrera A, Gee C, Wood A, et al. Introducing artificial intelligence in acute psychiatric inpatient care: qualitative study of its use to conduct nursing observations. Evidence-Based Mental Health 2020;23:34-38. This article was corrected after publication. The competing interests declaration has been amended to note that authors Oliver Gibson and Daniel Bayley are employees at Oxehealth, Oxford, UK. An ethical approval statement has been added to the article to specify that this project was approved as a quality improvement project by the Adult Directorate Quality Group at Oxford Health NHS Foundation Trust.

Barrera A, Gee C, Wood A, et al Introducing artificial intelligence in acute psychiatric inpatient care: qualitative study of its use to conduct nursing observations. Evidence Based Mental Health 2020;23. https://doi.org/10.1136/ebmental-2019-300136 This article was corrected after publication. The competing interests declaration has been amended to note that authors Oliver Gibson and Daniel Bayley are employees at Oxehealth, Oxford, UK. An ethical approval statement has been added to the article to specify that this project was approved as a quality improvement project by the Adult Directorate Quality Group at Oxford Health NHS Foundation Trust.

Psychological Science, Volume 37, Issue 10, Page 705-720, October 2026. We explored the impact of shared experiences on enjoyment, focusing on the role of facial expressions. Participants (N= 190, aged 18–35, recruited in Israel) listened to humorous audio clips with a friend or alone, while their facial expressions were ...

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Psychological Science, Ahead of Print. Alister et al. (2025) reported individual differences in the extent to which people find source-dependent and source-independent claims persuasive, but an exploratory analysis showed no discernible relationship between these individual differences and ...

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The “No to Execution Tuesdays” campaign, in protest against the rising wave of executions, has entered its 141st week, and political prisoners in 66 different prisons in Iran have gone on a hunger strike. These prisoners, by standing against the government’s “death machine,” protested the execution of at least 22 people in the past week, […]

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