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The British Journal of Psychiatry

Royal College of Psychiatrists

Preprints posted in the last 30 days, ranked by how well they match The British Journal of Psychiatry's content profile, based on 21 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

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A network meta-analysis of randomised controlled trials of antipsychotic medications to assess their comparative efficacy and tolerability in autistic people

Deb, S.; Limbu, B.; Lopez Lopez, J. A.; Roy, M.; Murugan, M.; Roy, A.; Brizard, B. A.; Santambrogio, J.

2026-05-14 pharmacology and therapeutics 10.64898/2026.05.11.26352928 medRxiv
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BackgroundA high proportion of autistic people receive off-license antipsychotic medication, often in the absence of a mental illness, primarily for behaviours that challenge, which is a public health concern. Although meta-analyses have been published recently, there is a lack of a comprehensive network meta-analysis to inform clinicians about the relative efficacy and safety of antipsychotic medications. AimsTo conduct a network meta-analysis of available RCTs of antipsychotic medications involving autistic participants to assess the relative efficacy of different antipsychotics and their adverse effects. MethodWe searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts, and full papers, extracted data, and assessed their quality. ResultsWe analysed data from 22 RCTs involving 1562 autistic people. The largest mean difference with 95% confidence interval in the Aberrant Behaviour Checklist-Irritability (ABC-I) score compared with placebo was from the combined intervention with risperidone and parent training: -11.16 (-15.13, -7.18), followed by risperidone: -7.59 (-9.22, -5.95), and aripiprazole: -5.59 (-7.18, -4). The largest effect on Clinical Global Impression-Improvement (CGI-I) scores was from risperidone, 7.65 (2.17, 27.04), followed by aripiprazole, 7.02 (1.92, 25.72), compared with placebo. Risperidone (4; 1.57, 10.21) and aripiprazole (2.77; 1.20, 6.39) had significantly higher odds ratios for adverse effects, but aripiprazole showed the least weight gain. ConclusionsCombined parent training and risperidone followed by risperidone and aripiprazole showed the best effects on the ABC-I score, whereas risperidone and aripiprazole showed the greatest effect on the CGI-I score. However, risperidone and aripiprazole showed significantly increased adverse effects.

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Diagnosis provision by young people's mental health services: a comparison with epidemiological data

Lewis, S. J.; Meehan, A. J.; Akiba, M.; Arseneault, L.; Byford, S.; Caspi, A.; Clark, B. R.; Downs, J.; Ford, T. J.; Fisher, H. L.; Koenen, K. C.; Moffitt, T. E.; Newbury, J. B.; Odgers, C. L.; Pritchard, M.; Simonoff, E.; Danese, A.

2026-06-05 psychiatry and clinical psychology 10.64898/2026.05.28.26354156 medRxiv
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Background Little is known about the provision of diagnoses to young people with mental health disorders. We investigated diagnosis provision by NHS mental health services, focusing on 17-year-olds in South London between 2009-2024, and compared with estimated disorder prevalence. Methods To examine diagnosis provision in the population, we extracted diagnosis data from records of the NHS mental healthcare provider serving South London, using the Maudsley Biomedical Research Centre Clinical Record Interactive Search application; we then compared these data with the corresponding population size, obtained from the Office for National Statistics. To assess diagnosis provision in those with mental health disorders, we compared diagnosis data with the number of young people estimated to have met criteria for a disorder, derived from epidemiological interview data collected in the Environmental Risk (E-Risk) Longitudinal Twin Study and weighted according to characteristics of 17-year-old South Londoners. To assess diagnosis provision in those with mental health disorders within health services, we compared diagnosis data with the number estimated to have met criteria for a disorder and used any health service for their mental health, again derived from weighted E-Risk Study data. Findings Of 17-year-olds from South London in 2009-2024, 4.0% (n=8,958/223,404) had a diagnosis in mental health records during the previous year. This diagnosis provision covered <1 in 16 of those estimated to have had a mental health disorder, and <1 in 4 of those estimated to have also used health services. Diagnosis provision was lower in girls than boys and in young people with Black/Asian/Mixed/Other ethnicity than those with White ethnicity, in those estimated to have had a mental health disorder and used health services. Interpretation These findings demonstrate gaps and biases in mental health diagnosis provision for young people, including within health services, and reveal the imperative need to strengthen young people's mental healthcare.

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Comparing outcomes following a first episode of psychosis in autistic and non-autistic people: a clinical retrospective cohort study

Ward, J. H.; Lewis, J. R.; Weir, E. M.; Ford, T. J.; Cardinal, R. N.

2026-06-02 psychiatry and clinical psychology 10.64898/2026.06.01.26354576 medRxiv
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Background. There is growing evidence to suggest a clinically significant overlap between autism spectrum conditions and psychotic disorders. Preliminary evidence suggest that autism diagnoses and autistic traits are associated with poorer outcomes following a first episode of psychosis. Methods. This study used data from the Cambridgeshire and Peterborough National Health Service Foundation Trust (CPFT) Research Database to examine clinical outcomes in autistic and non-autistic people following a first episode of psychosis. We describe patterns of community and inpatient service use, using descriptive statistics , Cox regression, binomial logistic regression, and negative binomial regression. Results. Data from 282 autistic and 7127 non-autistic people with psychosis were analysed. Autism was associated with greater community service use (use of mental health emergency lines, mental health detentions by police), as well as greater likelihood of psychiatric hospital admission (adjusted hazard ratio 1.34, 95% confidence interval 1.05 -1.7, p<0.05) and longer inpatient stays (median 111 versus 48 days, p<0.0001). Learning disability played a significant role in the utilisation of community and inpatient services, with lower rates of community service use but longer inpatient admissions. Conclusions. This study indicates a differing pattern of service use between autistic and non-autistic people following psychosis that warrants further research into how best to support autistic people with psychosis.

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Changes in the profile of adults diagnosed as autistic since 2010: population based studies in England and Sweden

Sadik, A.; Lundberg, M.; Khandaker, G. M.; Pardinas, A. F.; Lee, B. K.; Madley-Dowd, P.; Magnusson, C.; Rai, D.

2026-05-28 epidemiology 10.64898/2026.05.20.26353486 medRxiv
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Objective: To understand if sociodemographic and neuropsychiatric characteristics of people diagnosed with autism in the United Kingdom (UK) and Sweden have changed since 2010. Design: Cross-context population-based cohort studies. Setting: UK primary care records from 2010-2023 and Swedish population-wide register linkages from 2010-2021 Participants: 24,537,039 individuals age 16 or over, registered with general practices in the UK, including 141,119 with an autism diagnosis. 9,096,874 people age 16 or over in the Swedish Total Population Register, including over 100,817 with an autism diagnosis. Main outcome measures: Annual age-standardised incidence and prevalence of adult autism diagnoses within different sociodemographic groups. Annual age-standardised proportion of adults with new autism diagnoses, lifetime autism diagnoses, and no autism diagnoses, with prior records of other neuropsychiatric conditions or medications. Results: Incident adult autism diagnoses were consistently higher in Sweden than the UK, however incidence increased rapidly in the UK after 2020. Incident diagnoses increased fastest for 16-25-year-olds and females in both nations, as well as people in White ethnic groups in the UK and people with Swedish-born parents in Sweden. For example, in the UK in 2023 the age-standardised incidence of autism diagnoses among 16-65 years olds was 11 diagnoses per 10,000 person-years (95%CI: 10.7, 11.3) in the White ethnic group and 2.2 diagnoses per 10,000 person-years (95%CI: 1.9, 2.5) in the South Asian ethnic group. Over time there has been a consistent decline in the proportion of autistic adults with a prior diagnosis of epilepsy, psychosis and intellectual disability and an increase in the proportion with a prior diagnosis of ADHD, anxiety, depression and several other mental illnesses. For example, in the UK between 2010 and 2023 the age-standardised proportions of newly diagnosed autistic adults with prior records of epilepsy decreased from 10% (95%CI: 7.6, 13) to 4% (95%CI: 3.6, 4.5), while the proportion with records of anxiety increased from 28.7% (95%CI: 24.4, 33.6) to 58.3% (95%CI: 56.6, 60.1). Mental health conditions were generally more common in females and the reduction over time in intellectual disability was greater in females than males. Conclusions: The socio-demographic and neuro-psychiatric characteristics of individuals diagnosed as autistic have changed dramatically since 2010, a phenomenon observed both in the UK and Sweden. The extent to which these changes indicate nuanced recognition of autism or broadening of diagnostic practice needs investigation.

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Associations between screen use and antisocial behaviour in children and adolescents across development

Tesli, N.; Frei, E.; Rokicki, J.; Siqveland, J.; Shadrin, A. A.; Smeland, O. B.; Andreassen, O. A.

2026-05-12 psychiatry and clinical psychology 10.64898/2026.05.08.26352443 medRxiv
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BackgroundScreen use is pervasive in childhood and adolescence, yet its role in antisocial behaviour (ASB) remains uncertain. While cross-sectional studies consistently link higher screen use to elevated ASB, longitudinal evidence is mixed, and few studies have controlled adequately for prior behaviour and genetic liability. Thus, it remains unclear whether these associations reflect prospective influences of screen exposure, or underlying vulnerabilities shared with ASB. We investigated whether screen use is a modifiable risk factor or a marker of underlying vulnerability. MethodsWe analysed data from up to 41,562 children in the Norwegian Mother, Father, and Child Cohort Study (MoBa). ASB traits and ICD-10-based conduct disorder (CD) diagnoses were assessed at ages 5, 8 and 14 years, together with screen use (total exposure and modality). Cross-sectional logistic regression models examined associations between screen use and ASB traits/CD at each age, adjusting for sex and parental education. Polygenic risk scores for ASB (PRSASB) were used to assess genetic susceptibility and gene-environment interplay. Lagged logistic models tested whether screen use predicted later ASB, adjusting for prior ASB. Linear mixed-effects models examined developmental patterns across age. ResultsHigher screen use was positively associated with ASB traits and CD across all ages, with dose-response patterns across screen-use modalities. Social media showed the strongest modality-specific association at adolescence. In lagged models, screen use did not predict later ASB after adjustment for prior ASB. Longitudinal models showed significant but attenuating associations across development. PRSASB was independently and additively associated with ASB outcomes but did not interact with screen use. ConclusionsWe found that higher screen use was consistently associated with antisocial outcomes across childhood and adolescence. However, the absence of prospective associations after accounting for prior behaviour, together with independent genetic contributions, suggests that screen use may be better understood as a marker of underlying vulnerability rather than an independent driver of antisocial development.

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Stratifying the risk of transition to adult-onset psychiatric disorders in adolescents with anxiety

Dennison, C. A.; Shakeshaft, A.; Riglin, L.; Rice, F.; Andreassen, O.; Ask, H.; Havdahl, A.; Pine, D.; Martin, J.; Thapar, A.

2026-05-21 psychiatry and clinical psychology 10.64898/2026.05.15.26353293 medRxiv
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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.

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Environmental risk score as a predictor for 25-year symptom and functional trajectories in first episode psychosis

Lawal, S.; Liu, J.; McLeron, O.; Yang, Y.; Lian, W.; Vassos, E.; Kotov, R.; Jonas, K.

2026-05-18 psychiatry and clinical psychology 10.64898/2026.05.14.26353217 medRxiv
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Background and Hypothesis: Environmental exposures linked to schizophrenia may play a role in shaping long-term clinical outcomes among individuals with psychotic disorders. This study examined whether the Maudsley Environmental Risk Score (ERS), a cumulative measure of five established environmental risk factors, predicts trajectories of symptoms, cognition, and psychosocial functioning over 25 years following first hospitalization for psychosis. Study Design: Participants were drawn from the Suffolk County Mental Health Project, a longitudinal cohort of individuals with first-admission psychosis assessed six times over two decades. A total of 516 participants had sufficient ERS data and repeated assessments of symptoms (SAPS, SANS), cognitive ability, and functioning (GAF). Study Results: Linear mixed-effects models showed that higher ERS was significantly associated with lower global functioning ({beta} = -0.104, p = 0.008), an effect that remained consistent over time. ERS also predicted more severe and worsening reality distortion ({beta} = 0.082, p = 0.023 for intercept; {beta} = 0.005, p = 0.032 for slope of time). No significant associations were observed between ERS and cognitive ability, disorganization, or negative symptoms. Conclusions: These findings highlight the contribution of environmental risk to functional impairment and persistent positive symptoms across the course of psychotic illness. Incorporating ERS into clinical risk models may aid the identification of individuals likely to experience a more severe illness trajectory, and inform long-term treatment planning.

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Autistic Psychiatrists' Perspectives on Mental Healthcare for Autistic People: A Qualitative Study

Doherty, M.; Chown, N.; Martin, N.; Grosjean, B.; Shaw, S. C.

2026-06-02 psychiatry and clinical psychology 10.64898/2026.06.01.26354595 medRxiv
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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.

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Associations between Multiple Early Risk Factors and Cognitive Functioning at Time of Diagnosis in Children, Adolescents, and Adults with First-Episode Psychosis

Lemvigh, C. K.; Syeda, W.; Ambrosen, K.; Jepsen, J. R. M.; Nielsen, M. O.; Rydkjaer, J.; Bojesen, K. B.; Andersen, N. K.; Pantelis, C.; Pagsberg, A. K.; Glenthoej, B. Y.; Osler, M.; Fagerlund, B.; Ebdrup, B. H.

2026-05-13 psychiatry and clinical psychology 10.64898/2026.05.11.26352862 medRxiv
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BackgroundSchizophrenia is associated with widespread cognitive impairments. Several early risk factors for schizophrenia have been identified, and some studies suggest associations between these early risk factors and cognition, yet the literature is sparse in psychosis. MethodsClinical cohorts of child/adolescent and adult patients with first-episode psychosis (FEP) and healthy controls (HC) were linked with register-based information (N=276). Gestational age, Apgar scores, birth weight and length, parental age, and season of birth were extracted from the Danish medical birth registry. Cognition was assessed at time of diagnosis using BACS, CANTAB, and WAIS-III/WISC-IV. Missing data was imputed using MICE. Canonical correlation analysis (CCA) was used to examine patterns of associations. Post hoc analyses explored group differences according to diagnosis, age, and sex. ResultsCCA resulted in two significant patterns of associations. CCA1 was stable across imputations (r=0.44, p=.036, pmin= .017, pmax= .055), and constituted by a risk profile of lower maternal age, lower birth length, being small for gestational age, and lower birth weight and a cognitive profile of lower estimated IQ and poorer working memory, mental flexibility, processing speed, verbal fluency, and motor latency. The pattern was more expressed in FEP compared to HC and in adults compared to children. CCA2 was more unstable across imputations (r=0.38, p=.033, pmin=.003, pmax=.168) and constituted by a broad pattern of minor loadings. ConclusionCognitive functioning later in life is associated with multiple early risk factors, underscoring the complexity of developmental processes and the importance of the early developmental context in shaping cognitive trajectories.

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Developmental Associations Linking Childhood Trauma and Early Cannabis Use to Adolescent DNA Methylation and Psychotic-Like Experiences

Trotta, G.; Liu, Z.; Austin-Zimmerman, I.; Spinazzola, E.; Sideli, L.; Aas, M.; Rodriguez, V.; Li, Z.; Leung, B. M.; Li, Q.; Zhang, S.; Sham, P. C.; Vassos, E.; Bentall, R.; Walker, E. M.; Dempster, E.; Murray, R.; Di Forti, M.; Alameda, L.; Wong, C. C. Y.

2026-06-10 psychiatry and clinical psychology 10.64898/2026.06.09.26355257 medRxiv
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Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.

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Cultural engagement and mental disorders: A prospective negative control analysis of the English Longitudinal Study of Ageing with linked Hospital Episode Statistics

Qin, P.; Steptoe, A.; Fancourt, D.

2026-06-08 epidemiology 10.64898/2026.06.05.26354991 medRxiv
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Cultural engagement is associated longitudinally with better mental health and reduced depression incidence, but evidence has largely relied on self-reported symptoms and diagnoses, leaving uncertainty about clinically recorded disorders, and residual confounding remains a concern. Here, we examined whether cultural engagement (including going to cinemas, museums, galleries, exhibitions, theatre, concerts, or opera) predicts hospital-treated mental disorders in 8,274 adults aged 50 years or older from the English Longitudinal Study of Ageing. Participant records were linked to ICD-10 diagnoses in Hospital Episode Statistics and mortality records with follow-up of up to 20 years. In fully adjusted Cox models accounting for sociodemographic, lifestyle, and social factors and multiple testing, frequent cultural engagement was associated with lower risk of any mental disorders (HR 0.71, 95% CI 0.62-0.82, FDR adjusted P value<0.001), dementia (0.71, 0.56-0.89, FDR adjusted P value=0.010), substance misuse (0.75, 0.59-0.95,FDR adjusted P value=0.040), and mood disorders (0.73, 0.56-0.95, FDR adjusted P value=0.044), but not neurotic disorders. Associations persisted after excluding early incident cases and adjusting for baseline depressive symptoms and cognition, and showed robustness to unmeasured confounders. To further probe causality, eye disease, ear disease, and traumatic brain injury, which share similar socio-demographic profiles to mental disorders, were prespecified as negative control outcomes. Cultural engagement was not associated with any negative control outcomes. These findings provide triangulated statistical data to suggest that cultural engagement is associated with reduced risk of several clinically recorded mental disorders and support further testing of cultural engagement as a population mental health strategy.

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Mental healthcare utilisation and costs before and after dementia diagnosis: evidence from electronic health records

Eaglestone, G. L.; stoner, c.; pacella, r.; McCrone, P.

2026-06-03 epidemiology 10.64898/2026.06.02.26354695 medRxiv
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Objectives: To describe secondary mental healthcare utilisation and associated costs among patients diagnosed with dementia or mild cognitive impairment (MCI). Design: Retrospective cohort study using routinely collected electronic health record data. Setting: Secondary mental healthcare services within a large NHS mental health provider in South London, UK. Participants: Adults aged 18 years or older with a recorded diagnosis of dementia or MCI between 1 January 2010 and 31 December 2020. Patients surviving less than one year after diagnosis were excluded. The final cohort comprised 16,081 individuals. Primary and secondary outcome measures: Service utilisation and NHS mental health service costs during the 12 months before and after diagnosis, including inpatient, outpatient and memory clinic contacts. Results: The proportion of patients with at least one recorded mental health service contact declined from 91% in the 12 months before diagnosis to 69% after diagnosis. Among service users, mean NHS mental health costs increased from GBP 1,497 to GBP 2,177 per person following diagnosis (mean increase GBP 680; p<0.001), driven primarily by inpatient care. Dementia diagnosis, younger age, male gender, living alone, greater cognitive impairment and higher clinical symptom burden were independently associated with higher costs. Ethnic differences in service use and costs were also observed. Conclusions: Although overall service engagement declined following diagnosis, costs increased among those continuing to access care, indicating greater intensity of service use. Understanding patterns of secondary mental healthcare utilisation and associated costs may help inform planning and resource allocation within dementia services.

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Structured psychiatric care and psychosocial support during placebo participation: association with violent and domestic-violence offending in the ReINVEST trial

Akpanekpo, E. I.; Knight, L.; Gullotta, M.; Schofield, P. W.; Butler, T.

2026-05-18 psychiatry and clinical psychology 10.64898/2026.05.09.26352691 medRxiv
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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.

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Developing a Unified Criminal Justice Pathway into Drug and Alcohol Treatment from Police Custody: A Public Health Service Evaluation and Pathway-Design Project in Blackpool, United Kingdom

Badmos, A. O.; AbdulKareem, A. O.; Mills, J.; Gawne, A.; Idris, T.

2026-06-10 health systems and quality improvement 10.64898/2026.06.07.26355095 medRxiv
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Introduction: Blackpool, England's most deprived local authority, has the highest drug-related death rate in the country. People in police custody with problem substance use are a key Core20PLUS5 inclusion-health group, yet referral from the police into structured drug and alcohol treatment is fragmented and relies heavily on self-report. We evaluated the current police-to-treatment route in Blackpool and designed an evidence-informed unified pathway. Materials and Methods: A mixed-methods service evaluation and pathway-design project was conducted during a six-month General Practice / Public Health rotation. Routinely collected referral data from Horizon (the local specialist drug and alcohol service) covering the 47-month period from December 2019 to October 2023 were analysed. Findings were triangulated with national policy, the Project ADDER and Liaison and Diversion evaluations, and the international evidence on police-led pre-arrest diversion. Results: Of 5,900 total referrals into Horizon over 47 months, only 269 (4.56%) originated from the police. Police referrals accounted for fewer than 5% of monthly referrals in 30 of 47 months, for 5 to 9.9% in 16 months, and for >/= 10% in only one month (10.8%, December 2022). Blackpool recorded 76 drug-misuse deaths in 2019-21 (19.4 per 100,000, approximately four times the England rate). A six-step unified pathway is proposed: Initiate Referral (opt-out, from ADDER Police and Liaison and Diversion); Initial Assessment; Tailored Treatment Plan; Continuous Support; Collaboration and Monitoring; and Evaluation and Adjustment. Conclusions: Police contact is markedly under-used as a gateway to treatment despite Blackpool having the highest drug-related mortality in England. An opt-out, multi-agency pathway anchored in Core20PLUS5 has the potential to narrow the treatment gap, reduce re-offending, and address the structural health inequalities that drive premature mortality.

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Inflammation and late life depressive symptoms

Forbes, M.; Lotfaliany, M.; Miteku, B. M.; Yu, C.; Lacaze, P.; Isvoranu, A.-M.; Kang, M.; Nguyen, T.; Woods, R.; McNeil, J.; Neumann, J.; Mohebbi, M.; Berk, M.

2026-06-10 psychiatry and clinical psychology 10.64898/2026.06.05.26354416 medRxiv
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Background Low-level systemic inflammation has been associated with late-life depressive symptoms. Whether individuals with higher inflammation derive preventive benefit from low-dose aspirin therapy is unknown. Methods We performed a post-hoc analysis of the ASPiring in Reducing Events in the Elderly (ASPREE) randomised, double-blind, placebo-controlled trial. Baseline C-reactive protein (hsCRP) was measured in plasma and depressive symptoms were assessed annually using the Center for Epidemiologic Studies Depression 10 Scale with elevated symptoms defined as CES-D-10 >= 8. Participants with elevated depressive symptoms at baseline were excluded. We fitted population-averaged logistic generalised estimating equation models adjusted for baseline sociodemographic and lifestyle covariates, including an hsCRP x treatment interaction to test effect modification by aspirin. Results Higher baseline hsCRP was associated with increased odds of elevated depressive symptoms during follow-up (OR 1.07 per SD increase in hsCRP, 95% CI 1.03-1.11). Low-dose aspirin allocation did not modify the hsCRP-depressive symptoms association (interaction OR 1.02, 95% CI 0.94-1.10). Findings were similar after additional adjustment for comorbidity and other covariates. Conclusions In community-dwelling older adults during the ASPREE randomised trial period, higher baseline hsCRP was modestly associated with elevated depressive symptoms. There was no evidence that low-dose aspirin was associated with reduced risk of depressive symptoms among participants with higher baseline inflammation.

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Patient and caregiver lived experiences and mental health service engagement during first-episode psychosis in Uganda: a longitudinal mixed-methods study protocol

Oroma, P.; SSEMATA, A. S.; Ssembajjwe, W.; Auma, R.; Balinga, S.; Aujo, B. T.; Kaddu, A. K.; Ampiire, M.; Muhwezi, W.; Mwesiga, E. K.; Nakimuli-Mpungu, E.

2026-05-24 psychiatry and clinical psychology 10.64898/2026.05.21.26353795 medRxiv
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Introduction: Engagement with mental health services (MHCS) during the first episode of psychosis (FEP) is critical for symptom control, quality of life, and relapse prevention. However, disengagement rates remain high in Uganda with severe consequences for patients and caregivers. This study protocol describes a mixed-methods investigation which aims to examine the relationship between patients and caregivers lived experiences and mental health service engagement during first-episode psychosis. Methods and Analysis. The mixed-methods study will recruit 82 patients with first-episode psychosis and their primary caregivers from Butabika National Referral Mental Hospital in Kampala, Uganda. Inclusion criteria are ages 18-60, less than 12 weeks on antipsychotic medications, living in the greater Kampala Metropolitan Area, with a consenting caregiver. Caregivers must be an adult (> 18years) providing full-time care for at least 6 months prior. Patients with substance use disorders will be excluded. Qualitative data on the lived experiences of patients and caregivers will be collected using the draw-write-and-tell method, while quantitative data on service engagement and associated factors will be collected using semi-structured questionnaires. The data will be analysed using Stata version 18, and participants will be reimbursed for their time. Ethics and Dissemination. Ethical clearance has been obtained from the School of Medicine Research and Ethics Committee (SOMREC) Ref: Mak-SOMREC-2024-1002 and institutional approval from Butabiika National Referral Mental Hospital. All participants will provide informed consent prior to participation. Data will be de-identified and securely stored, with results disseminated through peer-reviewed academic publications, conferences and community stakeholder workshops.

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Life Beyond the Forensic Unit: A Systematic Review and Meta-analysis of Patient Reoffending, Hospital Readmission, and Mortality Rates Following Discharge to the Community

McLauchlan, J.; Marr, C.; Kemp, R.; Dean, K.

2026-05-29 forensic medicine 10.64898/2026.05.27.26354062 medRxiv
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Forensic patients often have complex and costly healthcare needs, even following discharge from secure care. However, little is known about their health and justice outcomes after community reintegration. To address this gap in the literature, we conducted a systematic review and meta-analysis to estimate the incidence of key post-discharge outcomes among community-discharged forensic patients, including any reoffending, violent reoffending, reconvictions, readmissions, all-cause mortality, and suicide. We systematically searched PsycINFO, Embase, CINAHL, Medline, PubMed, and ProQuest Dissertations from database inception to May 2025 (PROSPERO CRD42024529265). Random-effect meta-analyses were used to generate pooled incidence estimates, with heterogeneity quantified using prediction intervals. A total of 49 studies met inclusion criteria (total patient n = 18,871) and contributed to the meta-analyses. The pooled incidence rate per 100,000 person-years was: any reoffending 3,889 (95% CI 2,055, 7,359; 95% PI 290, 52,136); violent reoffending 1,851 (95% CI 1,229, 2,789; 95% PI 201, 17,068); reconvictions 3,291 (95% CI 2,591, 4,179; 95% PI 950, 11,394); readmissions 7,945 (95% CI 5,507, 11,463; 95% PI 1,225, 51,548); all-cause mortality 1,789 (95% CI 1,341, 2,388; 95% PI 673, 4,756); and suicide 407 (95% CI 319, 519; 95% PI 225, 735). Overall, the reoffending rate for forensic patients discharged to the community was lower than that reported for other cohorts of people charged with general and violent offences. However, despite typically receiving long admission periods, discharged forensic patients continue to experience high rates of readmission, all-cause mortality, and suicide relative to other psychiatric patient groups in the community. Together, our findings highlight a need for enhanced post-discharge suicide support for forensic patients living in the community to better facilitate successful, long-term reintegration.

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Mortality in people with attention-deficit/hyperactivity disorder (ADHD): Examining how risk is embodied in a pooling of two prospective cohort studies

Li, H.; Ford, T.; Warrier, V.; Bell, S.; Batty, G. D.

2026-06-09 epidemiology 10.64898/2026.06.08.26355148 medRxiv
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Background. Nascent findings suggest that people with attention-deficit/hyperactivity disorder (ADHD) experience higher rates of mortality. To date, study samples have been insufficiently well-characterized to examine the mechanisms via which this neurodevelopmental condition elevates mortality risk. Methods. We used data from the 2007 and 2011 waves of the US National Health Interview Survey, a general population-based cohort study comprising 52097 adults (28675 women) aged 18 years or older at baseline. ADHD diagnosis and an array of demographic, socioeconomic, lifestyle, and co-morbidity (somatic and psychiatric) covariates were self-reported. Findings. At baseline, compared with unaffected individuals, participants with ADHD were more likely to be socioeconomically disadvantaged, smoke cigarettes, consume alcohol, and report symptoms of psychological distress. A median 7.75 years of mortality surveillance (range: 7.25-12.25) gave rise to 6597 deaths from all-causes. After adjustment for age, sex, ethnicity, and survey year, ADHD was associated with a markedly elevated risk of death (hazard ratio [95% confidence interval]: 1.58 [1.20-2.09]). Statistical adjustment for socioeconomic circumstances (11% attenuation), physical co-morbidities (15%), and lifestyle factors (17%) had only a modest impact on the ADHD-death gradient, with the greatest explanatory power apparent for symptoms of depression and anxiety (58%). The magnitude of the association of ADHD with mortality was commensurate to that for several well-established risk factors such as poverty (1.66 [1.55-1.78]), hypertension (1.41 [1.32-1.51]), and diabetes (1.71 [1.59-1.85]) but somewhat lower than cigarette smoking (2.51 [2.29-2.76]) after controlling for age, sex, ethnicity, and survey year. Associations between ADHD and cause-specific mortality from cardiovascular disease, cancer, and chronic respiratory disease were inconclusive. Interpretation. In the present study, the influence of ADHD on total mortality appears to be largely embodied via a series of malleable characteristics, particularly mental illness. If confirmed elsewhere, these results raise the possibility that risk factor modification via standard pharmacological and behavioral interventions could help reduce rates of premature mortality in this patient group. Funding. This paper received no direct funding. GDB is supported by the UK Medical Research Council (MR/P023444/1) and the US National Institute on Aging (1R56AG052519-01, 1R01AG052519-01A1).

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Characterising the Stability of Polygenic Risk Scores: implications for risk stratification

Ferreira, A.; Lind, P. A.; Moody, H.; Hickie, I. B.; Olsen, C. M.; Whiteman, D. C.; Law, M. H.; Siskind, D. J.; Martin, N. G.; Medland, R. C.; Medland, S. E.

2026-05-20 genetic and genomic medicine 10.64898/2026.05.17.26353273 medRxiv
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Polygenic risk scores (PRS) improve progressively as genome-wide association studies (GWAS) increase in sample size and ancestral diversity, yet the effect of successive GWAS releases on individual PRS rankings remains poorly characterised. Here, we quantify how individual PRS rankings change across GWAS releases, whether those changes favour cases over controls, how consistently individuals maintain their relative position, and whether those in high-risk strata retain that classification over time. Using PRS derived from four GWAS releases for bipolar disorder, major depressive disorder, and schizophrenia in three Australian cohorts, we observed widespread bidirectional reclassification that exceeded the theoretical minimum of expected reclassification, and was directionally consistent with case-control status when discriminative performance improved. Rank variability was substantial and uniformly distributed across all levels of risk, rank persistence was limited across releases, and retention of high-risk classifications was variable across disorders and largely accounted for by the inter-release correlation. These findings demonstrate that individual PRS rankings are dynamic and shaped by progressive improvements in effect-size estimates, carrying important implications for PRS-based risk stratification strategies that rely on stable classifications in psychiatric research and clinical practice.

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Computational Linguistic Alignment in Psychosis from Naturalistic Clinical Interviews

Olarewaju, E.; Voppel, A. E.; Meister, F.; El Mouslih, C.; Dzialoszynski, P.; PALANIYAPPAN, L.

2026-05-26 psychiatry and clinical psychology 10.64898/2026.05.24.26353973 medRxiv
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Background. Something in discourse with a person experiencing psychosis often "feels off" before formal assessment is completed, yet this disturbance has not been quantified at the level of ongoing dyadic conversation. Prior work has largely treated patient speech in isolation, limiting our capacity to measure how communicative disruption emerges within clinical exchange. Methods. We applied a three-level decomposition of conversational alignment in 109 patients with psychotic disorders (26 female) and 60 healthy controls (22 female) at baseline and 12 months (n = 115). Register divergence (dAUCnorm) captured lexical distance between interviewer and patient; embedding-based synchrony (rembed) measured semantic trajectory coupling; within-speaker coherence was computed separately for each speaker. We used linear mixed-effects models adjusted for timepoint and participant clustering. Results. Patients showed significantly greater lexical-semantic divergence from the interviewer (d = 0.48, p < .001) and reduced embedding-based synchrony (d = -0.59, p < .001), both effects replicating at each time point. Critically, the interviewer's within-speaker coherence was reduced during conversations with patients (d = -0.33, p = .016), indicating that the disruption extends beyond the patient to the interaction itself. Register divergence tracked impoverished thinking and synchrony tracked disorganized thinking (both FDR-corrected q = .038). Group differences were persistent at 12 months, indicating a partially stable profile. Conclusions. Conversational alignment in psychosis reveals a dyadic failure of semantic coordination that destabilizes the interviewing clinician's coherence even when patient narrative continuity is preserved. These transcript-derived alignment metrics offer a scalable approach to quantifying interpersonal communicative function from routine clinical encounters.