BMJ Mental Health

BackgroundDepression and anxiety are common mental health conditions in the UK. NHS Talking Therapies offers evidence-based therapies and is the largest provider of treatment, yet, only 50% of patients recover. Accurate outcome prediction could identify those at risk of poor outcomes and support more personalised care. This study aimed to develop and internally validate multivariable prediction models using routinely collected data from a large, ethnically diverse sample to enable fair, data-driven treatment decisions. MethodsData included 30,999 adults who completed high-intensity therapy at a single NHS trust between 2018 and mid-2024. Seven NHS post-treatment outcomes were modelled: reliable improvement, recovery, and reliable recovery for both depression and anxiety, and also functional impairment at the end of treatment. Predictors measured at baseline included sociodemographic and clinical characteristics. Models were developed using elastic net logistic regression and internally validated using bootstrap resampling. ResultsThe sample was predominantly female (73%) with a median age of 34; 57% identified as White and 22% as Black. Models showed moderate to good discrimination (AUC 0.63-0.77) and strong calibration. Key predictors aligned with clinical expectations, including baseline symptom severity, unemployment, benefit receipt, reporting a disability or long-term condition, psychotropic medication use among other sociodemographic factors. ConclusionsThis study highlights the potential of data-driven tools to inform clinical decisions and treatment stratification in NHS Talking Therapies. Early identification of patients less likely to benefit from standard care could support timely review, monitoring, or tailored interventions. External validation and implementation research are needed to ensure generalisability and equity in care.

Background: The NHS Improving Access to Psychological Therapies (IAPT) programme, now rebranded as NHS Talking Therapies, faces persistent capacity constraints with average wait times exceeding 90 days for cognitive behavioral therapy (CBT) in many Clinical Commissioning Group areas. AI-powered CBT platforms have been introduced as a digital adjunct within stepped care, yet longitudinal evidence on anxiety symptom trajectories and their predictors in routine NHS settings remains limited. Objective: To model individual anxiety symptom trajectories among patients referred to an AI-powered CBT platform within NHS primary care, identify distinct trajectory classes, and examine patient-level and practice-level predictors of differential treatment response using multilevel growth curve modeling. Methods: A prospective cohort study was conducted using linked clinical and administrative data from 6,284 patients (aged 18-65) referred to the CalmLogic AI-CBT platform across 187 general practices in four NHS England Integrated Care Systems (ICSs) between April 2023 and September 2025. Patients completed GAD-7 assessments at baseline, 4 weeks, 8 weeks, 12 weeks, and 24 weeks. Three-level growth curve models (assessments nested within patients nested within practices) with random intercepts and random slopes were fitted. Growth mixture modeling (GMM) was subsequently applied to identify latent trajectory classes. Predictors were examined at Level 2 (patient demographics, baseline severity, comorbidities, digital literacy, engagement intensity) and Level 3 (practice deprivation index, list size, urban/rural classification, and IAPT wait time). Results: The unconditional growth model revealed a significant average linear decline in GAD-7 scores of -0.94 points per month (p < .001), with substantial between-patient variation in both intercepts (variance = 14.82, p < .001) and slopes (variance = 0.38, p < .001). Significant between-practice variation accounted for 8.7% of intercept variance (ICC = 0.087). Growth mixture modeling identified four distinct trajectory classes: Rapid Responders (28.4%, steep early decline stabilising by week 8); Gradual Improvers (34.1%, steady linear decline through 24 weeks); Partial Responders (22.8%, modest early improvement followed by a plateau at clinically significant levels); and Non-Responders (14.7%, minimal change or slight deterioration). Higher baseline severity, female gender, and greater module completion predicted membership in the Rapid Responder class. Practice-level IAPT wait times exceeding 90 days independently predicted faster improvement trajectories (coefficient = -0.31, p = .003), suggesting that AI-CBT has its greatest incremental value in capacity-constrained areas. Patients in the most deprived quintile showed slower trajectories (coefficient = 0.22, p = .011) despite equivalent engagement levels, indicating a deprivation-related treatment response gap. Conclusions: AI-powered CBT platforms integrated within NHS primary care produce significant anxiety symptom reduction on average, but treatment response is heterogeneous, with four distinct trajectory classes identified. The finding that longer IAPT wait times predict better AI-CBT outcomes supports the platform's positioning as a scalable bridge intervention for capacity-constrained services. The deprivation-related response gap warrants targeted support strategies for patients in the most disadvantaged communities.

IntroductionDespite evidence supporting child and adolescent cognitive behavioural therapy (CBT) globally, interventions remain largely unavailable within public systems. This gap requires implementation models integrating development, training, and scalability research within real-world settings and changes in management structures. Here we developed and implemented manualised psychotherapeutic protocols through a national capacity-building initiative in Greece. MethodsWe designed a structured implementation pathway conducted through the Child and Adolescent Mental Health Initiative (CAMHI), a public-private partnership involving clinical and academic institutions across Greece: (1) pre-implementation research through national reviews and national surveys of health professionals; (2) co-development and iterative pilot implementation of evidence-based interventions through supervised practice within the National Health System; and (3) dissemination research supporting scalability and institutionalisation within public structures. ResultsPre-implementation research identified gaps in the availability of clinical protocols in Greek services; a survey of 120 psychologists and psychiatrists indicated the need for psychotherapeutic training. Three evidence-based protocols were co-developed: CBT for anxiety (6-12 years), CBT for depression (12-17 years), and behavioural parent training (BPT) for disruptive behaviour (4-14 years). During a three-stage pilot, 45 clinicians delivered interventions to 140 cases (anxiety n=52; depression n=25; BPT n=63); 117 (83{middle dot}5%) completed treatment. Significant symptom reductions were observed for anxiety (d=-2{middle dot}92; RCADS-25), depression (d=-1{middle dot}79, RCADS-25), and disruptive behaviour (d=-2{middle dot}3, SNAP-IV), with 63%, 38% and 44% showing reliable improvement at the treatment endpoint. A train-the-trainer model is under implementation for national scale-up. Institutionalisation includes integration into child and adolescent psychiatry curricula. Sustainability safeguards were established through Law 5015/2023, with the Ministry of Health assuming operations by 2027. DiscussionPilot results demonstrate the feasibility of evidence-based psychotherapeutic interventions embedded within real-world child and adolescent services in Greece. Integrated implementation approaches provide a viable pathway for developing, refining, and scaling clinical manuals within public health provision.

ObjectiveTo charactertise emergency department (ED) use among young people with bipolar disorder (BD) and compare patterns to those observed in anxiety, depressive, and psychotic disorders. Design, setting and participantsData linkage study using administrative ED presentation records (January 2020 to October 2020) and a transdiagnostic youth mental health cohort of 2243 individuals aged 12-30 years in New South Wales, Australia. Main outcome measuresED presentation patterns (any presentation, frequency, and rates) and reasons for presentation (mental health-related and non-mental health-related). ResultsOf the 354 young people with BD, 309 (87.3%) presented to an ED at least once. ED presentation rates were higher for BD than for anxiety (incidence rate ratio [IRR]=1.82, p<.001) and depressive disorders (IRR=1.32, p<.001), but similar to psychotic disorders (IRR=0.91, p=.379). Differences were primarily driven by mental health-related presentations. Recurrent mental health presentations were associated with illness progression (clinical stage and functional impairment) rather than diagnosis. However, the likelihood of mental health-related presentations remained higher in BD compared with anxiety and depressive disorders after adjustment. ConclusionsYoung people with BD have high rates of ED use, comparable to those with psychotic disorders. Although mental health-related presentations are more common in BD than in anxiety and depressive disorders, recurrence is largely explained by markers of illness progression. These findings highlight the need for community-based services that provide continuous and coordinated care for young people with complex mental health needs.

Background: Observational studies have consistently reported associations between social media use (SMU) and poorer mental health outcomes; however, such designs cannot establish causality. This study synthesised evidence from randomized experiments to estimate the effects of restricting SMU on mental health outcomes. Methods: A systematic search was conducted across MEDLINE, Embase, PsycINFO, and Cochrane CENTRAL to identify experimental trials evaluating interventions that constrained SMU for at least 24 hours and included an unconstrained control condition. Multilevel random-effects meta-analyses were used to synthesise effect estimates. Prespecified meta-regressions explored study-level moderators, and population-level impact fractions were estimated relative to global SMU prevalence. Results: From 7,784 screened records, 37 reports representing 35 distinct studies were included (pooled N = 7,160). Most interventions lasted one to three weeks and targeted college-aged youth. Pooled estimates favoured SMU constraints across outcomes, with magnitude and precision varying by domain. Confidence intervals were entirely above zero, consistent with a beneficial response for depressive symptoms (g = 0.22; 95% CI, 0.12 to 0.32), perceived stress (g = 0.15; 95% CI, 0.01 to 0.29), anxiety symptoms (g = 0.19; 95% CI, 0.05 to 0.34), fear of missing out/nomophobia (g = 0.14; 95% CI, 0.04 to 0.24), and well-being (g = 0.36; 95% CI, 0.10 to 0.63). Heterogeneity was substantial for several outcomes (I2 > 75%). In bivariate meta-regressions, higher baseline SMU was associated with larger effects for anxiety symptoms ({beta} = 0.13; 95% CI, 0.03 to 0.22), and longer interventions were associated with larger effects for depressive symptoms ({beta} = 0.16; 95% CI, 0.02 to 0.30). Inferences revealed that a short-term reduction in SMU globally could plausibly mitigate 17.5% and 15.4% of depressive and anxiety symptom cases, respectively. Conclusions: Experimental design-based evidence supports the causal case for an effect of SMU on mental health, with constraints producing improvements across multiple outcomes and no evidence of harm. Population-level inferences suggest that even individually modest effects may translate into meaningful public health benefits given the high prevalence of SMU exposure. These findings suggest that reducing SMU may represent a low-intensity, low-cost, scalable strategy to support mental health and improve well-being.

BackgroundEarly Intervention for Psychosis Services (EIPS) enhance outcomes for individuals experiencing their first episode of psychosis (FEP). However, in low-resource settings, there is limited knowledge about i) the pathways patients take to access EIPS, ii) the proportion and factors associated with acceptance of referral to EIPS, and iii) if different pathways to EIPS services affect clinical outcomes. Ugandas first EIPS, the Specialised Treatment Early in Psychosis Service at Makerere University Hospital (STEP_MaKH), presents a unique opportunity to explore these important questions. AimsWe aimed to examine the pathways to EIPS, the factors associated with referral to specialised psychosis care and the impact of initial treatment-seeking behaviour on long-term symptom remission and quality of life. MethodsWe conducted a multiple-method study. Pathways to care were assessed retrospectively using the WHO Encounter Form among adults with FEP eligible for referral to STEP_MaKH. Among those who completed referral and enrolled in STEP_MaKH. Symptom severity and quality of life were followed prospectively for 12 months. Modified Poisson regression identified predictors of referral completion. Kaplan-Meier methods and Cox proportional hazards models examined time to symptom remission and time to achieving a good quality of life. ResultsOf the 187 adults with first-episode psychosis eligible for referral to STEP_MaKH, Native/religious healers (n = 86) were the predominant first point of contact. Only 56 (29.9%) accepted referral to STEP_MaKH. Participants referred from Mulago National Referral Hospital more likely to enrol than those referred from Butabika (RR = 4.7; 95% CI: 2.90-7.87). Longer delays from first treatment contact were associated with reduced likelihood of reaching STEP_MaKH (RR = 0.99 per month; p = 0.041). After enrolment, symptoms improved rapidly with 60% achieving PANSS remission by Month 1, and fewer than 10% remained non-remitted by Months 2-3. In adjusted Cox models, participants initially seen by mental health workers achieved remission more quickly than those initially seen by non-medical personnel (HR = 1.48; 95% CI: 1.05-2.10). Older age was associated with slower remission (HR = 0.94; p = 0.023). Quality of life improved over the follow-up period, with earlier attainment of good quality of life among those initially managed by mental health workers. ConclusionsPathways to care for FEP in Uganda are complex and culturally mediated, with substantial attrition before specialised early psychosis care is reached. Referral completion is strongly shaped by referral site and by delays in the care pathway. Once in specialised care, clinical outcomes improve rapidly, and initial contact with mental health workers is associated with faster symptom remission and earlier gains in quality of life. Strengthening referral systems, reducing pathway delays, and developing collaborative detection-and-referral links with community and frontline providers are key priorities for optimising early psychosis outcomes in low-resource settings.

Introduction People with bipolar disorder (BD) and concurrent opioid use disorder (OUD) experience more severe clinical outcomes, including higher mortality, treatment complexity, and worse psychiatric symptoms, yet they are underserved due to a lack of tailored clinical guidelines and limited supporting research on competing treatment options. While pharmacological treatments for BD are well-established, their use varies widely across settings, and their effectiveness in individuals with co-occurring OUD is unclear. We propose parallel population-based studies to emulate randomized controlled trials to assess the comparative effectiveness of pharmacological treatment options for BD among people with OUD in British Columbia and Ontario, Canada, 2010-2023. Methods and analysis We propose emulating a series of parallel target trials using linked population-level health administrative data for all individuals aged 18 years or older diagnosed with both BD and OUD and who initiated treatments for BD between 1 January 2010 and 31 December 2023. All analyses will be conducted in parallel in British Columbia and Ontario. We propose a series of four successive target trial emulations, comparing (i) lithium versus non-antipsychotic mood stabilizers such as divalproex, lamotrigine, and valproic acid; (ii) lithium versus 2nd generation antipsychotics with mood stabilizing properties such as risperidone, olanzapine, aripiprazole, and quetiapine; (iii) lithium versus combination treatments such as lithium and divalproex, lithium and olanzapine, lithium and aripiprazole, lithium and quetiapine, divalproex and olanzapine, and olanzapine and quetiapine; (iv) lithium and valproate (LATVAL) versus lithium and olanzapine, lithium and aripiprazole, lithium and quetiapine, divalproex and olanzapine, and olanzapine and quetiapine. Incident user and prevalent new user analyses are planned for proposed target trials (i)-(iv), pending sufficient data. Stratified analyses will be conducted for BD-I, manic and depressive phases of BD illness. We propose an initiator analysis (intention-to-treat, conditional on medication dispensation) to determine the effectiveness of the treatments and per-protocol analyses to determine the efficacy of the treatments after dealing with treatment switching and recommended dose adjustment. The outcomes will include psychiatric acute-care visits (hospitalizations and emergency department visits), BD treatment discontinuation and all-cause mortality. Subgroup and sensitivity analyses, including cohort and study timeline restrictions, eligibility criteria modifications, and outcome reclassifications, are proposed to assess the robustness of our results. Executing analyses in parallel across settings using a co-developed protocol will allow us to evaluate the replicability of findings. Ethics and dissemination The protocol, cohort creation, and analysis plan have been classified and approved as a quality improvement initiative by the Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups, clinical groups and decision-makers, national and international clinical guideline developers, presented at international conferences, and published in peer-reviewed journals.

Background Autistic people experience disproportionately high rates of co-occurring mental illness and suicide, yet mental healthcare services routinely fail to meet their needs. Patients unrecognised as autistic are at risk of ineffective or harmful treatment. Autistic psychiatrists occupy a unique position: as members of both medical and autistic communities, they offer dual insider perspectives that may directly shape patient outcomes. Despite being the second largest specialty group in Autistic Doctors International (ADI), this workforce remains largely unrecognised and underutilised. This study examines autistic psychiatrists' perspectives on mental healthcare for autistic people. Methods Loosely structured interviews were conducted with seven senior autistic psychiatrists across child and adolescent, adult, and liaison psychiatry, recruited from a psychiatry-specific subgroup of ADI. Data were analysed using reflexive thematic analysis: codes related to patient care and mental health services were extracted and analysed as a focused subset. Outcomes Nine themes were identified: autistic-to-autistic therapeutic rapport; benefit of recognition and diagnosis; early recognition and education as preventive factors; iatrogenic harm from non-recognition and systemic pathways to misdiagnosis; knowledge gaps and stereotypes; inaccessible services; resource constraints and diagnostic thresholds; autistic psychiatrists as an underutilised resource; and pathways to change. Interpretation Autistic psychiatrists' dual insider positionality affords a unique and under-acknowledged vantage point on what autistic patients experience and where mental healthcare fails them. The mental health burden autistic people carry is substantially shaped by systems not designed for them. Embedding neurodiversity-affirmative practice, closing training gaps, reforming diagnostic pathways, and recognising autistic psychiatrists as a clinical and epistemic resource offer a coherent pathway to improving mental health outcomes for autistic people.

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

Depression is accompanied by considerable comorbidity and excess mortality. We examined multimorbidity data using the validated pharmacy-based Rx-Risk Comorbidity Index and examined healthcare costs associated with chronic illness burden in the Australian Genetics of Depression Study (AGDS). Australian Pharmaceutical Benefits Scheme (PBS) record linkage for 15,890 AGDS participants was available from 01/07/2013-31/12/2017. Forty-six health morbidities were inferred by mapping the prescription data using Anatomical Therapeutic Chemical Classification System codes and PBS Item Codes. Morbidity prevalence rates were then compared with an unselected 10% Australian representative population sample (10PCT) with PBS claims data available from 01/07/2010-31/12/2014. The average number of inferred comorbidities was higher among AGDS participants (4.6 {+/-} 2.9) than 10PCT individuals (3.0 {+/-} 3.0). Excluding depression, 89.1% of AGDS participants had one or more inferred comorbidity, most commonly pain (51.0%), inflammation/pain (40.3%), and anxiety (32.3%). In the AGDS, the number of comorbidities was higher among women compared to men and positively correlated with participant age, BMI, number of depressive episodes experienced, and annual health care costs. Compared to participants with no inferred comorbidities, the median annual health care costs were ~65% higher among those with 2-3 comorbidities. This study highlights the patterns of health morbidities experienced by individuals living with depression and shows that this chronic disease burden is significantly associated with increased health costs to the individual and the health system.

BackgroundAI-powered cognitive behavioural therapy (AI-CBT) tools hold significant promise for addressing the global mental health treatment gap, yet sustained user engagement remains critically low. While patient attitudes and experiential factors have been qualitatively documented, the psychological mechanisms through which AI literacy translates into long-term engagement remain poorly understood. Existing systematic evidence highlights trust, perceived therapeutic alliance, and stigma as salient themes, but no large-scale quantitative study has modelled these as a mediated pathway. ObjectiveThis study aimed to (1) examine whether trust in AI systems and perceived therapeutic alliance mediate the relationship between AI literacy and sustained AI-CBT engagement, and (2) determine whether mental health stigma moderates these mediated pathways. MethodsA cross-sectional national online survey was conducted in the United Kingdom (N = 1,247). Eligible adults (18+) with a history of anxiety or depression who had used an AI-CBT tool in the preceding 12 months were recruited via stratified random sampling. Structural equation modelling (SEM) with moderated mediation was conducted in R (lavaan 0.6-17). Moderated mediation was evaluated using the PROCESS macro framework adapted for SEM, with 5,000 bootstrap replications for bias-corrected confidence intervals. Model fit was assessed using CFI, TLI, RMSEA, and SRMR indices. ResultsThe final SEM demonstrated excellent fit (CFI = 0.967, TLI = 0.959, RMSEA = 0.043 [90% CI: 0.036-0.051], SRMR = 0.052). AI literacy exerted a significant indirect effect on sustained engagement through trust in AI ({beta} = 0.213, SE = 0.031, p < .001) and perceived therapeutic alliance ({beta} = 0.187, SE = 0.028, p < .001). Mental health stigma significantly moderated the trust[-&gt;]engagement pathway ({Delta}R2 = 0.042, p = .003), with the indirect effect being stronger among individuals with lower stigma scores. The total indirect effect accounted for 58.4% of the total effect of AI literacy on engagement. ConclusionsAI literacy promotes sustained AI-CBT engagement primarily through its effects on trust and perceived therapeutic alliance, pathways that are attenuated by mental health stigma. These findings underscore the need for stigma-reduction interventions and AI literacy programmes as implementation strategies. Findings have direct implications for the design and deployment of AI-CBT tools across UK NHS digital mental health services.

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

Mental illness poses a substantial global burden, yet existing psychotherapies and psychopharmacologies often produce limited outcomes. Psychedelic assisted therapies have emerged as potential transdiagnostic interventions. In particular, 3,4 methylenedioxymethamphetamine assisted therapy (MDMA AT) has generated interest for its rapid psychological effects and potential to enhance psychotherapy outcomes. However, the incremental efficacy of MDMA AT relative to control interventions across transdiagnostic outcomes remains unclear. Further, there have been emerging concerns regarding harm reporting quality in MDMA AT clinical trials. We conducted a systematic review and meta analysis of MDMA AT randomized controlled trials. Eleven publications representing eight controlled trials with 10 analyzed subgroups (n = 295 participants) were included in meta-analyses. Two additional secondary publications were included for harm reporting syntheses (k = 13 total). Across 114 extracted effect sizes, MDMA AT demonstrated a significant moderate-to-large incremental reduction in psychopathology relative to controls (g = 1.03, 95% CI [0.46, 1.60]), though heterogeneity was high (I squared = 76%). Incremental effects were larger versus inert placebos (g = 1.27) than active controls (g = 0.75). Symptom specific analyses indicated strong incremental effects for trauma reduction (g=1.46 [95% CI: 0.67, 2.25]) and smaller non-significant effects for depression (g=0.51 [95% CI: -0.06, 1.08]). Harm reporting quality synthesis showed only 23% of publications met high-quality reporting standards. Overall, MDMA AT demonstrates potential transdiagnostic efficacy, but small samples, confounding factors, and mediocre harm reporting highlight the need for larger more transparent clinical trials.

Task-sharing approaches have shown promise in low-resource settings, yet few culturally adapted interventions have been systematically evaluated for forcibly displaced populations. Since 2016, over 1.7 million Venezuelans have migrated to Peru, facing significant barriers to healthcare and elevated risks of anxiety, depression, and post-traumatic stress disorder (PTSD). This protocol describes COMPASS (Cognitive-behavioral Open-source Mental-health Program Adapted for migrants, Sustainably delivered by lay providers and Supported by evidence). COMPASS is a transdiagnostic, open-source cognitive behavioral therapy program co-designed with forcibly displaced populations. This protocol describes the procedures for an ongoing randomized pilot trial with n = 90 forcibly displaced Venezuelan people (Clinicaltrials.gov: NCT06635486). COMPASS guides, or lay providers, trained through an intensive apprenticeship model, will deliver 6-12 weekly remote sessions. Primary outcomes include changes in anxiety, depression, and PTSD symptoms, assessed with validated Spanish-language measures. Secondary outcomes include feasibility (recruitment, retention, fidelity) and acceptability (therapist and participant ratings). Exploratory outcomes will examine integration, migration experiences, and demographic moderators of intervention effectiveness. Analyses will follow the intention-to-treat principle, using descriptive statistics and regression models to evaluate symptom trajectories across baseline, post-intervention, and 3- and 6-month follow-ups. This study represents the first effectiveness evaluation of an open-source, lay-delivered CBT program tailored for forcibly displaced people in Peru. Findings will inform feasibility, acceptability, and preliminary effectiveness of COMPASS, with potential to expand scalable, culturally relevant mental health services for forcibly displaced populations in resource-constrained settings worldwide.

Objective: Neuropsychiatric presentations are common across neurological and mental health services but they are often inadequately covered by core clinical psychology and clinical neuropsychology training. Consequently, we aimed to identify components for a neuropsychiatry curriculum for clinical psychologists using a Delphi process. Method: We completed a three-round e-Delphi study with 19 experts (clinical psychologists, neuropsychologists, psychiatrists, neurologists, individuals with lived experience of neuropsychiatric disorders). Round 1 collected ratings on 80 syllabus items derived from textbook reviews, conference topics, and a scoping review of neuropsychiatry syllabuses. Items failing to reach consensus were refined, and new topics added via free-text suggestions. Rounds 2 and 3 repeated rating and thematic analysis, culminating in a consensus meeting where items were classified as core or supplementary. Consensus thresholds were set at mean>=2.0, mean distance from the mean<=0.2, and => 75% agreement for final decisions. Results: The process yielded 40 core and 38 supplementary syllabus items. Core topics include autoimmune and neuroinflammatory disorders, delirium, functional neurological disorders, neuropsychiatric sequelae of epilepsy, stroke, traumatic brain injury, dementia, and multidisciplinary working, among others. Supplementary items covered background knowledge of less frequent but still prevalent disorders as well as competencies in interpreting clinical data alongside conceptual and historical issues. The final component list reflects both clinical competencies and emerging areas of practice, emphasising assessment, formulation, psychological interventions, cultural considerations, and medicolegal aspects. Conclusions: The e-Delphi derived curriculum provides a framework for neuropsychiatric competencies for postgraduate psychology training with modification needed for application in diverse healthcare settings.

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

Background Escalating mental health service demands have created a need to better identify young people most likely to require continued support from mental health services at the transition between childhood and adulthood. Anxiety is the most common adolescent mental health condition, yet its clinical significance and prognosis are not well understood. We aimed to examine the risk of young adult-onset psychiatric disorders in individuals with an adolescent anxiety disorder, and identify stratifiers of risk of subsequent psychiatric disorders in this group. Methods Individuals from the Norwegian Mother, Father, and Child Cohort Study (MoBa) with linked health records and aged 18 or over as of the 31st December 2023 were included. Those diagnosed with any ICD-10 anxiety disorder when aged 10-17 years were defined as having an adolescent anxiety disorder (n=2107, controls n=47,582). Polygenic scores (PGS) for psychiatric and neurodevelopmental conditions were calculated using LDpred2. Anxiety, comorbidities, and parental psychiatric history were defined through linked ICD-10 diagnoses. Sex was defined through linked records. Individuals were defined as having a young adult-onset psychiatric disorder if they first received any new psychiatric diagnosis aged 18-24. Results Adolescent anxiety diagnosis was associated with increased risk of all adult-onset psychiatric disorders (HR= 2.33-8.65). Post-traumatic stress disorder PGS, parental history of severe mental illness, and female sex were associated with increased risk of transition to a young adult-onset psychiatric disorder in people with an adolescent anxiety disorder. Conclusions Adolescent anxiety greatly increases the risk of a psychiatric disorder during the transition to adult life. Clinicians should consider female sex and parental psychiatric history when prioritising young people with anxiety for adult mental health service support. Future research needs to further consider whether polygenic scores would aid risk stratification in clinical practice.

Background: Participants in the ReINVEST randomised placebo-controlled trial of sertraline, conducted among men with high trait impulsivity and histories of violent offending, received structured clinical contact throughout the trial, including psychiatric assessments, nursing consultations, crisis support, and referrals to mental health and external services. We estimated the effect of placebo trial participation, compared with non-participation after baseline and single-blind run-in, on violent and domestic-violence reoffending. Methods: This prespecified secondary analysis included men from the ReINVEST trial pathway who completed baseline assessment and entered the single-blind run-in phase but did not proceed to randomisation, to inform the counterfactual. Violent and domestic-violence offences were identified from linked administrative records over 12- and 24-month follow-up periods. The adjusted difference in offending was estimated using two independent analytical approaches accounting for baseline differences. Additional analyses examined whether the effect varied by baseline clinical and criminal-history characteristics, whether pre-randomisation external referrals explained selection into placebo participation, and whether post-randomisation external referrals accounted for any part of the estimated effect. Results: Placebo trial participation was associated with lower offending across both outcome domains and follow-up periods. Placebo-standardised mean count differences for violent offending were -0.19 (95% confidence interval [CI] -0.38, -0.04) at 12 months and -0.22 (95% CI -0.51, -0.05) at 24 months. Corresponding differences for domestic-violence offending were -0.37 (95% CI -0.81, -0.14) at 12 months and -0.49 (95% CI -0.92, -0.22) at 24 months. The association was more apparent among men with a documented psychiatric history and, for domestic-violence offending, among those with higher baseline anger, irritability and aggression. Pre-randomisation referrals did not explain selection into placebo participation or materially alter the estimates. Post-randomisation referrals were observed in both groups, remained more common in the placebo group, and did not account for the observed association. Conclusion: Placebo participation in this trial involved sustained clinical contact and psychosocial support beyond exposure to inactive medication, and these non-pharmacological components may have contributed to lower reoffending. In placebo-controlled trials involving populations with high psychiatric morbidity and limited continuity of coordinated care, the clinical content of placebo participation should be explicitly characterised in trial design and interpretation.

Background: While growing enthusiasm for the therapeutic potential of classic psychedelics has led to a rise in non-clinical use, attention to persisting adverse effects has emerged with delay. A subset of individuals reports persisting complications such as hallucinogen persisting perception disorder (HPPD), depersonalization/derealization disorder (DDD), anxiety and depression. Yet few medical services are equipped to address these complications. Aims: This qualitative study examines how societal, medical, and media discourses shape the experiences of individuals with persisting psychedelic-related complications, focusing on help-seeking trajectories. Methods: Thirteen semi-structured interviews with adults experiencing persisting psychedelic-related psychological symptoms (four women, nine men, age 19-49 years; HPPD (n = 10), DDD (n = 6), depression (n = 1), and anxiety (n = 1)) were conducted within a larger study on these complications. Data were analysed using reflexive thematic analysis. Reporting followed the COREQ guidelines. Results: Three interrelated themes emerged: (1) The dissonance between expectation and harm - idealised media and scientific portrayals of psychedelics shaped initial use and complicated recognition of adverse outcomes; (2) Stigma, silence, and self-blame - prohibitionist discourse and internalised shame significantly inhibited help-seeking; and (3) Between systemic absence and self-organised support - participants encountered clinical unpreparedness and epistemic dismissal, which often led them to rely on online peer communities and self-management strategies. Positive clinical encounters, characterised by professional expertise and nonjudgmental engagement, were experienced as helpful. Conclusions: Adequate clinical and conceptual frameworks for persisting psychedelic-related complications are lacking. An interdisciplinary, experience-informed approach integrating realistic risk communication, clinician training, and destigmatisation is required to support affected individuals.

Background Chronic pain and depression are leading causes of disability and frequently co-occur. Depression presents with diverse symptoms, but despite this variability, the prevalence of individual depressive symptoms in chronic pain and the genetic and causal associations linking these traits remain poorly characterised. Methods Using data from 142,688 age- and sex-matched UK Biobank participants, we compared depressive symptom severity levels and item-level Patient Health Questionnaire-9 (PHQ-9) prevalences, spanning affective, cognitive and somatic domains, between participants with and without chronic pain. Using genome-wide association study (GWAS) summary statistics of multisite chronic pain (MCP), major depressive disorder (MDD), and individual symptoms of depression, genetic correlations and bidirectional causal effects between MCP and depressive phenotypes (MDD and individual symptoms) were estimated via linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomisation (MR), respectively. Results Depression (at every severity level) was more common in the chronic pain group compared to controls, with the largest between-group difference for severe symptoms (7.50-fold increase). All individual depressive symptoms were at least 2.79 times as prevalent in chronic pain. Additionally, chronic pain had a significant and positive genetic correlation with MDD (rg = 0.59) and all depressive symptoms (rg = [0.24, 0.55]). MR supported a bidirectional causal association between MCP and MDD (MCP[-&gt;]MDD: OR = 1.85, pFDR < 0.001, MDD[-&gt;]MCP: {beta} = 0.17, pFDR < 0.001). At the symptom level, MR indicated bidirectional effects between MCP and anhedonia (MCP[-&gt;]anhedonia: OR = 1.60, pFDR < 0.001, anhedonia[-&gt;]MCP: {beta} = 0.08, pFDR = 0.005), and unidirectional effects of MCP on appetite/weight gain (OR = 1.90, pFDR = 0.022) and appetite/weight loss (OR = 1.63, pFDR = 0.005), concentration problems (OR = 1.63, pFDR = 0.044), and suicidal thoughts (OR = 1.46, pFDR = 0.021). Additionally, genetic liability to concentration problems was associated with a lower risk of MCP ({beta} = -0.04, pFDR = 0.022). Conclusion Chronic pain is associated with a marked depressive burden spanning all symptom domains. Shared genetic architecture and symptom-specific causal pathways, particularly involving anhedonia, highlight potential targets for improved treatment of comorbid chronic pain and depression.