BMJ Mental Health

Background Psychiatric diagnoses and psychotropic medication use among children, adolescents, and young adults have increased in high-income countries, with concerns about geographic variation. We described national trends and geographic variation in Denmark from 2010 to 2025 and developed an interactive online tool to explore these patterns. Methods We conducted a nationwide, descriptive, repeated cross-sectional register-based study of all Danish residents aged 0-24 years in 2010-2025 (n=2,930,744), using the Danish National Patient Registry and the Danish National Prescription Registry. We estimated annual incidence, prevalence, and, for selected diagnoses, lifetime prevalence, by age and sex, and age- and sex-standardised rates across regions, health councils, and municipalities. We assessed geographic variation using deviations from national means, coefficients of variation, Gini coefficients, and funnel plots. Findings Psychiatric diagnoses and psychotropic medication use increased from 2010 to 2025. The annual prevalence of attention-deficit hyperactivity disorder (ADHD) increased from 0.41 to 2.3 per 100 individuals, autism spectrum disorders from 0.20 to 1.2, and melatonin use from 0.14 to 3.0. ADHD and autism spectrum disorders were more prevalent among boys and anxiety disorders among girls. Sertraline use was also more prevalent among girls. Geographic variation was observed across diagnoses and psychotropic medications at regional, health council, and municipal levels. For example, lifetime prevalence of autism ranged from 1.3 to 5.9 per 100 across municipalities, and in 2025 regional coefficients of variation ranged from 0.11 (sertraline) to 0.41 (atomoxetine). Results can be explored in the interactive online tool (https://bupstat.sdu.dk/?lang=en). Interpretation Psychiatric diagnoses and psychotropic medication use increased among Danish children, adolescents, and young adults, with marked geographic variation. Descriptive data cannot establish the causes of this variation, but the findings identify areas for further review and support continued monitoring. Funding Best for Us project (www.bedstforos.dk), funded by the Novo Nordisk Foundation (NNF24SA0093635) and the Obel Family Foundation (69348).

Background: A comprehensive overview of how premature mortality in severe mental illness varies by socioeconomic position and healthcare utilization is lacking. Methods: We followed all Norwegian residents aged 30-79 years on January 1, 2008, through December 31, 2023. Nationwide registry linkage provided data on mental illness in primary and specialist care, educational attainment, and cause of death. We estimated the mortality gap as excess life-years lost from age 30 for depression, bipolar disorder, and schizophrenia compared with the general population, stratified by sex, healthcare utilization, and educational attainment. All-cause, external-cause, and natural cause mortality were assessed using competing risks. Results: The cohort comprised 2,486,836 individuals, including 483,933 with depression, 40,125 with bipolar disorder, and 21,963 with schizophrenia. Among men, the mortality gap ranged from 1.50 year (95% CI 0.36-3.34) among those with depression, non-inpatient care utilization, and university education to 19.86 years (18.34-21.36) among those with schizophrenia, inpatient care utilization, and less than high school education. Among women, the corresponding range was no gap to 18.16 years (17.03-19.53). Mortality gaps were generally larger with lower educational attainment and inpatient care utilization and increased from depression to bipolar disorder to schizophrenia. This pattern was consistent across sexes, diagnoses, healthcare utilization levels, and educational attainment levels and was most pronounced for natural-cause mortality. Conclusions: Premature mortality among people with severe mental illness forms a continuum across socioeconomic disadvantage, healthcare utilization, and diagnosis. Combining these measures can identify subgroups with the greatest mortality burden and may help target preventive interventions.

Background: Autistic people experience substantially higher rates of mental health conditions and are overrepresented in mental health services. However, most interventions and service models have been developed for non-autistic people, and evidence is needed as to whether there are disparities in outcomes. This systematic review aimed to compare outcomes between autistic and non-autistic people receiving the same mental health interventions or services. Methods: We conducted a systematic review following PRISMA guidelines (PROSPERO: CRD420251021068). We searched academic databases (MEDLINE, Embase, PsycINFO, PubMed, CINAHL), a grey literature database (HMIC), a trial registry (ISRCTN), preprint servers (medRxiv and PsyArXiv), Google, and Google Scholar, to identify relevant papers published 01/01/1992-30/04/2026. We conducted backwards and forwards citation searching and contacted experts. Study quality was assessed using a modified Critical Appraisal Skills Programme Cohort Study Checklist and the Autism-Inclusive Research Assessment (AIRA). Data were synthesised narratively, with random effects meta-analyses where appropriate. Results: Thirty-nine studies were included, comprising 4787730 participants, assessing outcomes of psychological therapies (n = 17) and multi-component or service-level approaches (n = 22). Nearly half (46.2%) were UK-based, and under a quarter (23.1%) included people with intellectual disabilities. Ten studies (25.6%) were rated low quality, twenty-two (56.4%) medium quality, and seven (17.9%) high quality. AIRA ratings highlighted concerns about research inclusiveness for autistic people, including limited involvement of autistic people and lack of validated or adapted outcome measures. Findings varied by intervention: for some, multiple large, higher-quality studies showed less favourable outcomes for autistic people (e.g., less improvement in symptoms or functioning, or higher rates of restrictive practices or acute service use). For other interventions, comparable or mixed outcomes were found across studies, with interpretation often limited by small samples. Conclusions: Mental health treatment outcomes for autistic versus non-autistic people varied across interventions and outcome types. Where significant differences were observed, these usually showed poorer outcomes for autistic people, although they generally reflected smaller improvements rather than a lack of benefit. Action is needed to improve the accessibility and appropriateness of mental health care for autistic people, supported by more high-quality, co-produced research across a broader range of countries and service contexts.

Early detection of individuals at clinical high risk for psychosis (CHR-P) improves access to preventive care. We developed and internally validated the E-DetectioN Tool for Emerging mental disoRders (ENTER), a multimodal digital screener designed to improve community identification of CHR-P compared with an established approach (PQ-16 cut-off). Participants aged 12-35 years from the UK and Italy completed the online ENTER screener, assessing attenuated psychotic symptoms, processing speed and environmental risk factors. Participants above the PQ-16 cut-off and a random subset below were assessed with the Comprehensive Assessment of At Risk Mental States (CAARMS). PQ-16 cut-off and ENTER models were developed using (penalised) logistic regression, random forest and extreme gradient boosting (XGBoost) within a repeated nested cross-validation framework with semi-supervised learning incorporating unlabelled data. Models were evaluated by discrimination, calibration and clinical utility. 2,522 participants completed the ENTER screener. 495 underwent CAARMS assessments. 124 (25.1%) met CHR-P criteria; 2,027 participants were not assessed with the CAARMS (unlabelled). ENTER showed improved discrimination (C=0.744, 95%CI: 0.697-0.790) compared to the PQ-16 cut-off (C=0.625, 95%CI: 0.570-0.682, p=0.003) and similar calibration (ENTER: slope=1.02, 95%CI: 0.78-1.32; PQ-16 cut-off: slope=0.39, 95%CI: 0.19-0.52, p=0.074). At a clinically relevant threshold, ENTER identified approximately 2 additional CHR-P individuals per 100 assessments compared with the PQ-16 cut-off. Compared with established PQ-16 cut-off pre-screening, ENTER showed higher performance for community identification of CHR-P individuals. Multimodal digital screening might support more informative community triage before specialist assessment. External validation and implementation studies are required to establish real-world clinical utility.

Background People diagnosed with severe mental illnesses (SMI) including bipolar disorder, schizophrenia and psychosis are disproportionately exposed to adverse social determinants of health, contributing to premature morbidity and mortality. Social prescribing aims to address social risk factors for poor health by linking patients in primary care to community activities. However, whether people with SMI access social prescribing through primary care remains unexplored. Aims To describe prevalence of, and sociodemographic characteristics associated with, social prescribing consultations in patients with SMI in primary care. Methods Using the UK Clinical Practice Research Datalink, we identified patients aged 18+ with a diagnosis of SMI between 2004-2019. We calculated the percentage of patients with SMI who received a social prescribing consultation between 2019-2023 and used logistic regression to examine associations between sociodemographic, health-related factors and social prescribing consultations and refusals. We used fixed effects analysis to determine whether a new diagnosis of SMI made between 2019-2023 was associated with an increased odds of receiving a social prescribing consultation. Results Among 112,334 patients with SMI, 0.8% received a social prescribing consultation in 2019 increasing to 9.5% in 2023. Between 2020-2023, older age (OR=1.18-2.34), being female (OR=1.16-1.31) and living in more deprived areas (OR=1.14-1.49) were associated with higher odds of receiving a social prescribing consultation amongst patients with SMI. Across all years, patients with SMI and depression (OR=1.32-1.92), diabetes (OR=1.19-1.35) or obesity (OR=1.17-1.54) also had increased odds. In 140,514 patients with time-varying SMI status, a new diagnosis of SMI was associated with higher odds of receiving a social prescribing consultation (OR=1.39, 95% CI 1.26-1.53). Conclusion Since 2019, social prescribing consultations among patients with SMI in primary care have increased and are reaching those in areas of higher deprivation and with greater health needs. Strategies to remove barriers to consultations among younger adults and males are still needed

Background Diabetes is common in people with bipolar disorder, particularly men. Both type 2 diabetes and bipolar disorder are associated with evening chronotype, and men of working-age have later chronotypes than women. However, it is not known whether elevated rates of diabetes in bipolar are explained by evening chronotype, nor whether sex differences in chronotype contribute to higher rates of diabetes observed in men with bipolar disorder. Aim To determine whether evening chronotype increases the likelihood of comorbid type 2 diabetes in bipolar disorder, relative to those with no mental health problems. Additionally, to determine whether any effect differs between men and women. Methods Using data from the Our Future Health cohort, we estimated odds ratios for type 2 diabetes by bipolar disorder diagnosis, chronotype, and their interaction, adjusting for relevant covariates. Results A total of 1,136,694 participants (N = 6,846 with bipolar disorder) were included in the adjusted models. Type 2 diabetes was independently associated with bipolar disorder and evening chronotype. There were no significant differences in the interaction effects of chronotype on the odds of type 2 diabetes in bipolar across the whole sample or when stratified by sex. Conclusions The high prevalence of type 2 diabetes in people (and in men, specifically) with bipolar disorder may be independent of evening chronotype.

BackgroundPsychotic-like experiences (PLEs) have been shown to increase the risk for mental health problems in later life, especially psychosis. Following previously raised methodological concerns about the assessment of PLEs in adolescents, this study sought to differentiate subtypes of PLEs and to explore their trajectories. MethodsLongitudinally matched data of 671 German adolescents from three surveys over the time span of one year were analysed. Four trajectories were identified, including persisting, subsiding, and emerging highly indicative PLEs (HIPs), and non-highly indicative PLEs (non-HIPs), and longitudinally compared in terms of associated distress, psychopathology, and substance use. A differentiated never PLEs group was considered as a control. ResultsThe persisting HIPs group reported greater distress than the non-HIP group over time and was consistently associated with higher rates of internalising symptoms. The subsiding HIP group showed significant reductions in distress and internalising symptoms over time, but no significant changes regarding externalising symptoms and substance use. There was no difference in the extent of substance use between the groups. ConclusionsScreenings of PLEs should be mindful of different subtypes of PLEs that indicate a greater associated risk of poor mental health. PLE screening should not stop at whether PLEs are present but ask which ones.

Introduction: Adolescents experience high rates of depression and anxiety, yet globally 80% of adolescents and almost all in low-and middle-income countries (LMICs) lack access to adolescent-friendly treatments. The African Youth in Mind (Y-MIND) set out to adapt the youth version of the Friendship Bench and assess its feasibility for delivery in Ghana. Methods: In this feasibility cluster randomised controlled trial, we recruited participants aged 15 to18 years with probable diagnosis of moderate to severe depression ascertained with the Patient Health Questionnaire (PHQ-9) total score > 9 from six Senior High Schools in Navrongo, Ghana. Schools were randomly allocated (1 to 2) to enhanced usual care (EUC) alone or EUC combined with Y-MIND, prior to recruitment of participants. Primary outcomes were feasibility (intervention delivery; conducting a fully powered trial). Secondary outcomes were intervention appropriateness, acceptability, and probable depression symptom severity and remission on the PHQ-9. Results: Between July and August 2024, we enrolled and allocated 67 participants (43 [64%] to the EUC plus Y-MIND group and 24 [36%] to the EUC alone group), of whom 64 (95.5%) completed the 5-month primary outcome assessment (41 [95.3%] in the EUC plus Y-MIND group and 23 [95.8%] in the EUC alone group). The feasibility of delivering the Y-MIND intervention from the perspective of adolescents had a mean score of 4.3 (0.5). Therapy quality score was 94.8% (95% CI: 93.0, 96.6), while therapy competence was 86.6% (95% CI: 81.2, 92.2). We observed initial clinical benefits, including lower severity of depressive symptoms among adolescents in the Y-MIND group as compared to those in the EUC group, with most participants achieving symptomatic remission at the month 5 follow-up. Conclusion: The Y-MIND school-based psychological treatment model demonstrated good acceptability and feasibility, with high recruitment, retention, treatment adherence, and provider competence. While preliminary findings indicate potential improvements in depressive symptoms, the study was not designed to establish effectiveness. These findings justify progression to a fully powered trial to determine clinical effectiveness, cost-effectiveness, and the scalability of the intervention within routine school settings in LMICs. Trial registration: Clinicaltrials.gov (NCT06740084).

Brief assessments reduce clinician and patient burden and increase utilization. Recently, five core depression symptoms (low mood, poor concentration, low self-worth, loss of interest, low energy) have been shown to be particularly sensitive to treatment effects in adults. How these core depressive symptom domains perform for screening or diagnostic purposes in youth is unknown. To address this question, we extracted five analogous symptom items from four widely used symptom assessment tools for children and adolescents (Child Behavior Checklist [CBCL], Youth Self Report [YSR], Parent General Behavior Inventory [P-GBI], and Adolescent General Behavior Inventory [A-GBI]) to create 5-item short forms. We evaluated their psychometric properties and diagnostic utility in a large (N=1185), racially diverse sample (48% Black youth) across community and academic outpatient mental health settings, with diagnoses established through LEAD consensus. All short forms correlated highly with full-length measures (r=.74-.92) and demonstrated comparable inter-item correlations (r =.19-.46). The short forms did not differ meaningfully from the full measures in correlations with psychiatric diagnoses, demographics, or diagnostic interviews. Area under the curve (AUC) values for identifying depression and any mood disorder diagnosis (determined by semi-structured diagnostic interviews) were fair to good (AUC=0.60-0.79), which were not worse than full measures, except for the P-GBI. The CBCL-5, YSR-5, P-GBI-5, and A-GBI-5 may be useful brief depression assessments in youth. How these five symptom domains perform as outcome measures in treatment deserves study.

Background: Self-harm is a frequent and challenging occurrence in adult inpatient psychiatric units. The use of restrictive practice to manage self-harm incidents continues to be widespread within mental health environments despite increasing national and organisational guidance to minimise its use. Aim: The aim of this project was to introduce and evaluate a continuous quality improvement programme to progressively reduce incidents of self-harm and the use of restrictive practice. The project was set in a female acute mental health inpatient unit. The project sought to embed improvements in an inpatient unit interventions, procedures, and culture and staff mindset, and move towards a sustained collaborative and positive therapeutic and communication-based approach. Methods: A retrospective service evaluation design was employed to assess differences in the number of incidents of self-harm, enhanced observation, seclusion, restraint and rapid tranquillisation in the period following the introduction of a continuous whole-systems multimodal interventional initiative in 2019. Pre- and post-initiation data were compared (2017/18 compared to 2019/2025) to evaluate improvement and whether this had been sustained. Data were analysed using descriptive statistics, including frequencies, percentages, and means. Results: Self-harm incidents reduced between 2017/18 and 2019, with a downward trend sustained between 2019 and 2025 (136 to 72 incidents respectively between 2019 and 2025; 47% reduction). A sustained reduction in the use of restrictive practice was shown in all domains pre- and post-initiation (2017/18 compared to 2025). Clinical implications: No one approach will successfully reduce self-harm and the use of restrictive practice. Approaches employed have to be multi-faceted, multi-interdisciplinary, collaborative, and blend together to deliver improvement. Sustained progress requires commitment to an iterative process of continuous collaboration, improvement and adaptation.

Importance. Anorexia nervosa (AN) is a severe metabo-psychiatric disorder with heterogeneous outcomes and elevated mortality. Characterizing severity trajectories may improve early risk stratification and targeted intervention. Objective. To identify AN severity trajectories using a register-based severity index (AN-RSI) and examine their associations with polygenic scores (PGS), preceding (prior to AN diagnosis) as well as subsequent (5 years post AN diagnosis) psychiatric and somatic disorders. Design. Population-based cohort study. Setting. Nationwide study in Denmark. Participants. Individuals born between 1969 and 2013 with diagnosed AN (N = 9,534 individuals). Genetic data were available in a subsample comprising 5,126 individuals. Exposures. Forty-one PGS indexing traits relevant to AN, and psychiatric and somatic disorders prior to AN diagnosis. Main Outcomes and Measures. The main outcomes of interest were the AN-RSI trajectories and psychiatric and somatic disorders 5 years post AN diagnosis. Results. Three trajectories were identified: "low and stable" (32.6%), "medium and stable" (53.5%), and "high increasing" (14.0%). The "low and stable" group was used as the comparison group for all analyses. Each 1 standard deviation (SD) increase in AN PGS corresponded with 13% greater odds of following the "high increasing" trajectory. Increases in BMI and attention-deficit/hyperactivity disorder PGS corresponded with 15% and 14% lower odds of following the "high increasing" trajectory, respectively. No preceding psychiatric or somatic disorders were significantly associated with trajectory assignment. In contrast, psychiatric and somatic disorders were more likely to occur subsequent to an AN diagnosis in those in the "high increasing" trajectory with odds ratios (OR) ranging between 1.73 and 3.81 for psychiatric disorders and between 1.61 and 5.38 for somatic disorders with a notable exception of obesity which showed a lower OR of 0.27. Conclusions and Relevance. Our findings hold significant clinical relevance by demonstrating that individuals with AN follow distinct severity trajectories that have different genetic risk as measured by PGS and clear differences in post-diagnosis morbidity patterns but no discernable differences in pre-diagnosis psychiatric or somatic morbidity. As the eating disorders genetics field progresses, incorporating PGS into comprehensive assessments at first presentation may aid in early identification, personalized intervention, and resource allocation for individuals at higher risk of developing a severe illness trajectory.

Background. Population-representative evidence on social inequalities in youth mental health from an intersectional perspective is limited. We investigated inequalities across multiple mental health outcomes among young adults and examined whether measures operated equivalently across social and intersectional groups. Methods. Cross-sectional analyses were conducted with 9,675 participants aged 23 years from the nationally representative UK Millennium Cohort Study (born 2000-2002). Self-reported outcomes included psychological distress (Kessler-6), probable serious psychological distress/'caseness' (Kessler-6 score [≥]13), psychological wellbeing (Short Warwick-Edinburgh Mental Well-Being Scale; SWEMWBS), past-year self-harm, and lifetime suicide attempts. Measurement invariance analyses assessed comparability of the Kessler-6 and SWEMWBS across groups. Intersectional MAIHDA examined inequalities by sex assigned at birth, ethnic identity/background, sexual identity, and childhood poverty. Young people with lived experience of mental ill-health and/or social discrimination contributed to study design, interpretation, and reporting. Findings. Large inequalities were observed across all outcomes, with the largest disparities by sexual identity, followed by sex assigned at birth, childhood poverty history, and ethnic identity/background. Across intersectional strata, predicted psychological distress ranged from -0.27 to 1.32 SDs, and psychological wellbeing from -0.54 to 0.11 SDs. Predicted prevalence varied 6.99-fold (9.81% to 68.55%) for psychological distress 'caseness', 6.84-fold (8.60% to 58.79%) for self-harm, and 22.10-fold (1.96% to 43.32%) for suicide attempts. Young people at the intersection of sexual minority status, female birth sex, childhood poverty, and some ethnic minority identities/backgrounds experienced particularly poor outcomes. Most inequalities showed cumulative patterns consistent with additive expectations, although some intersectional groups experienced better or worse outcomes than expected. Accounting for measurement differences revealed inequalities that were otherwise undetected. Interpretation. Findings highlight the large extent of mental health inequalities when multiple dimensions of social (dis)advantage are considered, and the need to address both the social conditions generating these inequalities and the methodological assumptions shaping how they are measured and understood.

Abstract Background The neuropsychiatric sequelae (cognitive deficits, anxiety and depression) post-COVID-19 exist as part of the spectrum of the multisystemic long COVID. People with these symptoms have been shown to have worse functional outcomes. Hence, this significantly impacts the economy, primarily due to productivity losses. Yet, the precise underlying pathogenesis remains unknown, as do any diagnostic or prognostic biomarkers. Aim This study aims to identify functionally impacted brain regions in those with post-COVID-19 neurological sequelae and to evaluate how alterations in brain function relate to acute serum inflammatory mediators and brain injury biomarkers. Methods The study will utilise data from the COVID-19 Clinical Neuroscience Study (CNS), a large UK multicentre study conducted during the pandemic. This sub-study will be a secondary analysis of the COVID-19 CNS, a prospective observational study that compared COVID-19-positive participants with negative controls. Participants had an MRI, blood tested for acute serum inflammatory mediators and brain injury biomarkers, and neuropsychiatric assessment (cognitron test, PHQ-9 and GAD-7) post-acutely and at follow-up. The DPABI (Data Processing & Analysis for Brain Imaging) toolbox will be used for pre-processing and analysis of the neuroimaging data (resting state functional MRI) to obtain regional homogeneity (ReHo). The association between ReHO and neuropsychiatric symptoms, acute inflammatory mediators and brain injury biomarkers will be explored. Regression models would be used to determine the risk and protective factors for developing these symptoms. Conclusion It is anticipated that the study will provide new insights into the functional basis of post-acute COVID-19 neuropsychiatric manifestations and identify new diagnostic biomarkers. Key words: Regional Homogeneity, COVID-19, functional MRI, neuropsychiatry, biomarkers

Objective: The Genetic Risk for Serious Mental Illness and Development ("Paisa Kids") Study is establishing a longitudinal cohort of 3,000 youth enriched transdiagnostically for risk for serious mental illnesses (SMI; i.e., schizophrenia, bipolar disorder, and severe depression) from the Paisa region of Colombia. Its objective is to clarify the early clinical, neurobehavioral, genetic, and environmental profiles associated with later SMI and distinguish transdiagnostic from disorder-specific pathways. This paper describes the study infrastructure, recruitment streams, and baseline assessment battery, and characterizes the first two-thirds of the cohort. Method: Youth aged 6-15 years are being recruited. Youth recruited for high SMI risk either have a first or second degree adult relative with a SMI diagnosis or a psychiatric diagnosis themselves identified through electronic medical records (EMRs) associated with later SMI. Lower-risk youth have a relative without a SMI diagnosis. Baseline measures include psychiatric and developmental history, neurobehavioral functioning, environmental exposures, and genome-wide genotyping. Psychiatric EMRs provide longitudinal follow-up. Results: Among 2,384 participants enrolled thus far (mean age=11.2 years, 45.0% female), 2,211 were recruited for high SMI-risk and 173 for lower SMI-risk. Overall, 73.2% met criteria for a history of one or more psychiatric disorders. Logistic regression comparing rates of diagnoses and ACEs between recruitment streams showed elevated rates of depressive and anxiety disorders, attention-deficit/hyperactivity disorder, oppositional defiant disorder, and several ACEs among high versus lower SMI-risk youth. Conclusion: Integrating multidomain phenotyping, genomic data, and longitudinal EMR follow-up, the Paisa Kids cohort provides a unique resource for investigating pathways of risk and resilience to SMI.

Objective: To identify speech features distinguishing adults with depression from healthy controls, evaluate whether these features track with depression severity during naturalistic treatment, and assess whether baseline speech features predict treatment response. Design: Cross-sectional group comparison (Objective A) followed by longitudinal evaluation in an independent sample (Objectives B and C). Candidate features surviving false discovery rate (FDR) correction in the cross-sectional analysis were carried forward to longitudinal and predictive analyses. Setting: A community mental health center in New York. Participants: Dataset I (cross-sectional): 82 adults with chart-diagnosed depressive disorders and 80 healthy controls (N=162), recruited via convenience sampling. Dataset II (longitudinal): 85 adults with depressive disorders followed for up to four timepoints over a mean of 10.4 weeks during naturalistic treatment; 63 with baseline PHQ-9 >=10 and at least one follow-up were included in prediction analyses. Recruitment occurred under protocols approved between 2020 and 2021. Interventions: None; participants received naturalistic clinical care. Outcome Measures: Cross-sectional: diagnostic group membership (depressive disorder vs. healthy control). Longitudinal: Patient Health Questionnaire-9 (PHQ-9) total score. Predictive: treatment response, defined as >=50% PHQ-9 reduction from baseline to last follow-up. Results: Across three speech tasks (journaling, picture description, phonemic fluency), 11 voice quality features, six shimmer variants and five harmonics-to-noise ratio (HNR) variants, survived FDR correction (all q<.05) in all tasks, with higher shimmer and lower HNR in the depressed group (largest adjusted effect beta=1.89, q<.001). In longitudinal analysis, one phonemic fluency voice quality feature was associated with PHQ-9 at FDR<.05 (maximum HNR beta=-1.43, SE=0.41, FDR=.006), with the remaining ten consistent in direction at FDR<.10; no speech x time interactions were significant. Sex moderated voice quality-depression associations in picture description and phonemic fluency. For treatment response prediction, phonemic fluency voice quality features achieved cross-validated AUC=0.727 [95% CI: 0.662, 0.792], comparable to clinical features alone (AUC=0.700-0.715); the combined model across all tasks and clinical features achieved AUC=0.730 [0.639, 0.820]. No pairwise AUC comparisons between predictor configurations reached significance after correction (all corrected p>.54). Conclusions: Voice quality features, particularly shimmer and HNR, were the most consistent speech correlates of depression across cross-sectional, longitudinal, and predictive analyses and across multiple speech tasks. These features are computationally simple to extract from brief recordings and showed preliminary predictive utility comparable to standard clinical variables. However, the modest sample sizes, chart-based diagnoses and heterogeneous treatment exposures preclude clinical application at this stage. Larger, prospectively designed studies with standardized recording protocols, structured diagnostic assessment, and recruitment at treatment initiation are needed before voice quality features can be recommended as clinical biomarkers.

Background: Cognitive impairment is a major determinant of functional outcome in psychotic disorders, yet the contribution of psychotropic medication is incompletely understood. This study aimed to determine whether personalised receptor-engagement profiles derived from prescribed psychotropic medications are associated with cognitive performance in individuals with psychotic disorders. Methods: We performed a cross-sectional study using clinical, cognitive, and medication data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes studies. In 1,067 (51.5% female) individuals with psychotic disorders, we estimated personalised receptor-engagement profiles based on the prescribed dose and known pharmacological properties of 49 psychotropic medications across 32 drug targets. Correlated receptor-target modulation profiles were summarized into seven pharmacological clusters. Extreme gradient boosting models were trained using repeated nested cross-validation, with the contribution of pharmacological profiles to predicted cognition quantified using out-of-sample SHapley Additive exPlanations (SHAP) values. Overall pharmacological contribution was tested using within-diagnosis permutation testing. Results: Estimated receptor-engagement profiles were significantly associated with cognitive performance independent of diagnosis. A receptor profile involving alpha2-adrenergic, dopaminergic (DRD4, DRD5) and several serotonergic receptors was associated with poorer cognitive performance, whereas dopamine transporter (SLC6A3) engagement was associated with better cognitive performance. Muscarinic receptor modulation was additionally associated with poorer verbal memory and motor speed, while the DRD2-containing receptor profile was not associated with cognitive performance after correction for multiple testing. Conclusions: Modelling psychotropic medications according to receptor pharmacology identified receptor-engagement profiles associated with cognitive performance in psychotic disorders. This framework may help identify receptor systems for future investigation as potential targets for cognition-enhancing therapies and support the development of personalised prescribing strategies.

BackgroundAtypical antipsychotics (AAPs) are increasingly prescribed for paediatric patients with autism spectrum disorder (ASD). However, pharmacovigilance data from Saudi Arabia remain scarce. The aim of this study is to detect and characterise signals associated with AAPs and assess gender- and age-related ADR reporting patterns. MethodsA retrospective cross-sectional study with disproportionality analysis was conducted on paediatric patients (0-19 years) using the Saudi Food and Drug Authority (SFDA) database (2021-2024). Disproportionality analyses were performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). Age and gender were assessed using odds ratios (ORs), with Firth penalized logistic regression to confirm associations. ResultsOverall, 701 ADR reports were analysed. Most involved males (59.91%) and children aged 0-9 years (82.88%). Olanzapine had the highest proportion of serious reports (44.44%). At the system organ class (SOC) level, signals included nervous system disorders with risperidone (ROR 32.61 [16.62-64.00]; PRR 3.49 [2.22-5.47]; IC025 0.08); cardiac and general disorders with quetiapine; haematological, metabolic, and psychiatric disorders with olanzapine; and gastrointestinal disorders with aripiprazole. Gender-adjusted analyses indicated significant variation in selected ADR signals across age groups, while no significant differences were observed by gender. ConclusionsThis study highlights disproportionality signals associated with AAP use in paediatric patients. Age-related ADR variation supports consideration of age-specific ADR monitoring within current paediatric recommendations. While these findings do not establish causality, they generate hypotheses for further evaluation. Regional pharmacovigilance may complement international paediatric safety monitoring frameworks.

Objective: Cognitive models of psychosis implicate maladaptive core schemas in the development and emergence of psychotic symptoms, but no study has tested temporal dynamics between schemas and psychotic symptoms in a large sample of clinical high-risk (CHR) youth. Given their sizable role in cognitive behavioral therapies, the first-line treatment for CHR youth, core schemas may be key to both symptom development and treatment in this population. Methods: Participants were 578 CHR individuals from the second North American Prodrome Longitudinal Study (NAPLS-2) assessed across five timepoints. Time-lagged mixed-effects models tested forward and reverse paths for each Brief Core Schema Scales subscale with both psychotic symptom and functioning changes, controlling for autoregressive effects, time-varying depression, and linear time. Results: Twenty of 36 schema outcome pairs showed significant prospective associations. Negative-other schemas were prospectively associated with worsening across nearly all psychosis symptom and functioning domains. Suspiciousness exhibited bidirectional associations with all four schema subscales. Grandiose ideas were uniquely prospectively associated with positive-self and negative-other schemas. Positive schemas were prospectively associated with decreases in suspiciousness, negative symptoms, and improvements in functioning. Effects were largely independent of depressive symptoms and robust across sensitivity analyses, with partial attenuation of self-schema effects on suspiciousness. Conclusions: Core schemas were prospectively associated with psychosis symptom and functioning change in CHR youth, with symptom-domain specificity and bidirectionality. These findings extend cognitive models of psychosis into CHR syndromes and highlight schemas as potentially modifiable treatment targets to improve outcomes in this population.

Objective: Brief measures of depressive symptoms and family psychiatry history may support the identification of youth who warrant further assessment, but their interpretation requires population-based measurement evidence. This study evaluated the Very Quick Inventory of Depressive Symptomatology (VQIDS) and Family Index of Risk for Mood (FIRM) in the BENCHMARK 2025 national survey. Method: The sample consisted of 2,252 parent reports for children aged 6-18 years and 1,008 linked adolescent self-reports aged 12-18 years. Analyses examined VQIDS dimensionality, reliability, item functioning, age- and sex-based norms, and informant agreement, alongside FIRM score distributions, alternative scoring approaches, and associations with depressive symptoms. Results: VQIDS findings supported a single dimension and good internal consistency, with greatest IRT precision at elevated symptom levels and no practically meaningful differential item functioning across age or sex. Two-week stability was moderate, and parent-adolescent agreement was lower within more symptomatic subsets. FIRM totals showed stronger cross-informant agreement and retest stability. Family history scores were associated with higher VQIDS percentiles and discriminated scores at or above the 90th percentile across informants (AUROC = .670-.698). FIRMs associations were strongest with internalizing symptoms, although evidence was mixed for mood specificity. Conclusions: These findings provide a measurement and normative foundation for brief depressive symptom assessment and support family history as a complementary correlate of symptom elevation. Diagnostic and prospective prediction utility require further evaluation.

Individuals with autism spectrum disorder (ASD) and co-occurring mood or psychotic disorders face substantially elevated suicide-attempt risk, but prior research is largely limited to population-level incidence and cross-sectional risk-factor studies, leaving unclear whether individual-level, prospective prediction is possible in this population. We conducted a retrospective prediction model study using Epic Cosmos electronic health record (EHR) data from 322,879 individuals with ASD and co-occurring mood or psychotic disorders to predict suicide attempts at the next clinical encounter using only information available at or before the preceding encounter. Five machine-learning algorithms were compared, with performance evaluated across discrimination, calibration, and clinical utility. All algorithms achieved strong discrimination using the full predictor set (AUROC 0.87-0.91). A parsimonious feature set (22 predictors) matched or exceeded full-model performance, with extreme gradient boosting (XGBoost) achieving the highest discrimination and standardized net benefit post-ablation (AUROC = 0.90; AUPRC = 0.34), though net benefit was comparable for elastic net and logistic regression. A prior suicide attempt was the strongest individual predictor. Decision-curve analysis indicated that model-guided decisions provided greater net benefit than treating all or no individuals across a broad range of clinically plausible thresholds. These findings demonstrate that near-term suicide-attempt risk can be predicted with high decision utility in this high-risk population using data already captured in routine care, suggesting a feasible basis for future EHR-based clinical decision-support tools.