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      BMJ Mental Health
        • Psychiatric admission in female survivors of childhood and young adult cancer: a whole population retrospective study
          Background The last 40 years have seen a substantial improvement in overall survival from cancer in children and young people. There is limited information on psychiatric wellbeing in female survivors of cancer at a young age. Objective In this 40-year population-based linkage study, we set out to determine the incidence of first psychiatric admission compared with a non-exposed age-matched control. Methods Scottish cancer registry records from 1981 to 2012 were linked to psychiatric admissions, maternity and death records from January 1981 to September 2018 using the unique personal Community Health Index number allocated to each person in Scotland. For each exposed subject, three age and deprivation matched controls from the population were selected. The primary exposed group was all females with a cancer diagnosis at age <25 years and no previous pregnancy and no psychiatric admission before cancer diagnosis. The main outcome measure is admission to a psychiatric hospital with a mental health diagnosis. Findings Female cancer survivors had a significantly lower cumulative incidence of first psychiatric admissions than matched controls over the 38 years of follow-up for the cohort (p<0.05). The relative risk of a first psychiatric admission at 25 years from cancer diagnosis was 0.72 (0.56–0.89). Conclusion Overall, we have shown that young cancer survivors are less likely than age-matched controls to have a psychiatric admission after cancer diagnosis. In particular, psychiatric admissions for mood disorders, neuroses, personality disorders and substance use are significantly less likely in the cancer survivors. Clinical implications The experience of cancer treatment and survival in young females may reduce the risk of psychiatric admission in later life.
          Wallace, W. H. B., Kelsey, T. W., Morrison, D. S., Marwick, K. F., Anderson, R.
        • How epistemic trust, mistrust and credulity relate to mental health, personality pathology, treatment engagement and relationship in psychotherapeutic and psychiatric settings
          Background Epistemic trust describes the capacity to appropriately identify others as reliable and relevant sources of information, an ability closely linked to attachment and social learning. Epistemic disruption can manifest as heightened suspicion (mistrust) or excessive reliance (credulity) vis-à-vis others, affecting mentalizing abilities and increasing vulnerability to psychopathology and maladaptive traits. These interdependent and multidirectional dynamics are pivotal to therapeutic learning, and thus to therapeutic change. Objective This study examined associations between epistemic trust and disruption, markers of psychopathology, therapeutic relationship quality and treatment-seeking behaviour. Method A naturalistic sample of 912 participants, recruited via a mental health app, completed the Epistemic Trust, Mistrust and Credulity Questionnaire, along with self-reports capturing internalising symptoms, personality functioning, maladaptive traits and the perceived therapeutic relationship within the previous 6 months. Treatment-seeking behaviour and the number of sessions utilized in the past year were further explored—both in psychotherapeutic and psychiatric contexts. Findings Epistemic mistrust and credulity showed consistent relationships with markers of psychopathology. Higher epistemic (mis)trust correlated with more positive (negative) ratings of various aspects of the therapeutic relationship, including genuineness, realism, expectations, congruence and responsivity—over the past 6 months. Epistemic trust positively predicted the amount of psychotherapy sessions, while epistemic mistrust negatively predicted treatment-seeking, both controlled for personality dysfunction. Epistemic credulity predicted mental health app use—all assessed retrospectively (past year). Conclusion The results encourage further in-depth exploration of trust-related aspects of the therapeutic alliance and investigation of mechanisms of change in therapeutic processes that may facilitate the transition from mistrust and credulity to trust. Clinical implications Even though the magnitude and direction of effects remain to be clarified, patients with epistemic mistrust may enter a self-reinforcing cycle of reduced openness and ineffective mentalizing, potentially impacting therapeutic effectiveness. Interventions targeting epistemic disruption and impaired personality functioning seem to be crucial for improving therapeutic outcomes, including psychopharmacological treatment effectiveness.
          Bröcker, A.-L., Nolte, T., Böttche, M., Knaevelsrud, C., Kerber, A.
        • Health economics analysis of restrictive school smartphone policies in secondary schools in England (SMART Schools)
          Background Many countries have introduced restrictive smartphone policies in schools, aiming to improve adolescent health and educational outcomes. However, whether these policies represent value for money to schools remains unclear. Objective The aim of this study was to estimate the costs and quality of life and mental well-being outcomes associated with restrictive and permissive phone policies in secondary schools in England, and conduct an economic evaluation to determine whether restrictive phone policies are cost effective for schools. Methods A cost–utility analysis was conducted as part of a cross-sectional study on school smartphone policies in England (SMART Schools), comparing schools with restrictive (recreational phone use not permitted) and permissive (recreational phone use permitted) policies. Outcomes were valued using quality-adjusted life years (QALYs) and mental well-being adjusted life years (MWALYs). Costs were estimated from the school’s perspective and comprised staff time spent on policy implementation. Mixed effects and linear regression models were used to estimate incremental differences in outcomes and per pupil costs. Findings 815 pupils (aged 12–15) from 20 schools (13 restrictive, 7 permissive) were included in a complete case analysis. Differences between restrictive and permissive schools in incremental QALYs (0.009, 95% CI –0.014 to 0.032) and MWALYs (–0.004, 95% CI –0.044 to 0.036) were minimal. Time implementing and enforcing policies was equivalent to 3.1 FTE staff in restrictive and 3.3 FTE staff in permissive schools. The incremental difference in per pupil school year cost was –£94 (95% CI –£229 to £41). The cost-effectiveness acceptability curve indicated a 90% probability of restrictive policies being cost effective at a threshold of £20 000 and £30 000 per QALY. Conclusions Restrictive school policies were associated with minimal differences in quality of life or mental well-being of pupils. However, they may offer some cost savings to schools by reducing staff time spent managing phone-related activities. Clinical implications School policies and practices require development to address the significant amount of time teachers spend managing phone use.
          Perry, S. J., Goodyear, V. A., Pallan, M., Adab, P., Fenton, S., Michail, M., Patterson, P., Randhawa, A., Sitch, A. J., Wade, M., Al-Janabi, H.
        • Development and external validation of machine learning approaches for risk prediction of cardiovascular disease in individuals with schizophrenia: a nationwide Swedish and Danish study
          Background Currently available cardiovascular disease (CVD) risk prediction tools may underestimate the risk in individuals with schizophrenia. Objective To develop and externally validate 5-year CVD risk prediction models for people with schizophrenia using large-scale register data in Sweden and Denmark with a machine learning (ML) approach. Methods Individuals with a diagnosis of schizophrenia, aged 30 and older and without prior CVD, were followed for up to 5 years. We investigated whether adding additional health-related and socio-demographic predictors to the established CVD risk factors improved predictions and compared ML models with logistic regression. External validation was performed across countries. Findings A lasso penalised logistic regression including additional predictors achieved the highest predictive performance, both on Swedish and Danish data, while complex ML models with interaction terms did not provide additional improvements. The area under the receiver operating characteristic curve (AUC) on the internal validation data was 0.745 (95% CI (0.742 to 0.749)) in the Swedish model, and 0.722, 95% CI (0.719 to 0.726) in the Danish model. External validation showed similar performance, yielding an AUC of 0.746, 95% CI (0.741 to 0.751) using the Danish model on the Swedish data, and an AUC of 0.720, 95% CI (0.712 to 0.726) using the Swedish model on the Danish validation data. Conclusions Incorporating additional health-related information, such as psychiatric comorbidities and medication use, improved 5-year CVD risk prediction for people with schizophrenia in both countries. Clinical implications The models can be deployed between Denmark and Sweden without loss of performance compared with training a model on each country.
          Nielsen, S. D., Dobrosavljevic, M., Andell, P., Chang, Z., Clemmensen, L. K. H., Larsson, H., Benros, M. E.
        • Genetic and neuroanatomical correlates of bipolar disorder in high-risk youth
          Objectives Bipolar disorder (BD) often begins in adolescence, a period marked by dynamic neurodevelopment. However, the neurobiological basis from genetic risk and subthreshold symptoms to diagnosed BD remains unclear. Methods We conducted a cross-sectional analysis using data from the Recognition and Early Intervention of Prodromal Bipolar Disorders cohort (NCT01863628), including 392 participants aged 12–25 years with a balanced sexual distribution, stratified into five groups: offspring of patients with BD with (OBDs, n=48) or without (OBDns, n=62) subthreshold symptoms, individuals without BD family history but with subthreshold symptoms (nOBDs, n=63), patients diagnosed with BD (n=133) and healthy controls (HCs, n=86). Cortical thickness relative to HC was assessed using high-resolution T1-weighted images and FreeSurfer V.7.3.2. Gene expression patterns were derived from the Allen Human Brain Atlas, and partial least squares regression, along with gene enrichment analyses, were applied to link cortical alterations with underlying transcriptomic profiles. Findings Cross-sectional analyses revealed graded cortical thickness differences across the BD risk spectrum, with patients with BD showing the most pronounced deviations and high-risk individuals with subthreshold symptoms displaying intermediate features relative to HCs. Cortical changes were significantly associated with spatial gene expression patterns, particularly in genes involved in mitochondrial ATP production, oxidative phosphorylation and synaptic signalling. Gene set enrichment revealed that BD-specific cortical thinning correlated with downregulation of excitatory synaptic pathways and excitatory neuron-related gene expression. Conversely, high-risk individuals exhibited upregulation of both excitatory and inhibitory neuronal markers. Developmental transcriptomic enrichment further linked significant genes to mid-childhood and adolescence. Discussion By identifying distinct transcriptomic signatures associated with cortical thinning at different stages, our findings underscore the potential of transcriptomic markers for early detection and intervention in BD. Clinical implications The findings highlight the potential for using transcriptomic markers for early detection and intervention, suggesting that identifying these markers could lead to improved outcomes for at-risk adolescents. This research has the potential to inform clinical practices and policies aimed at early screening and preventive strategies for BD.
          Wang, J., Liu, X., Lam, B. Y.-H., Lu, W., Shao, R., Li, X., Wang, R., Xu, F., Chen, J., Cai, A., Goldstein, B., Du, F., McIntyre, R. S., Wu, J., Lin, K.
        • Parents coping with their adolescents negative emotions following internet-delivered emotion regulation therapy for adolescents with non-suicidal self-injury disorder: a secondary analysis of a randomised clinical trial
          Background Non-suicidal self-injury (NSSI) among adolescents is linked to adverse outcomes for youth and their families. While parental involvement is considered essential in treating adolescent NSSI, the effects on parents remain unclear. Objective To evaluate if Internet-delivered Emotion Regulation Individual Therapy for Adolescents (IERITA) adjunctive to treatment as usual (TAU) is superior to TAU alone in improving parental coping with adolescents’ negative emotions, the durability of potential effects and whether reductions in parents’ minimising of their adolescent’s emotions mediate adolescent outcomes. Methods 166 adolescents with NSSI disorder (93% female; mean (SD) age=15.0 (1.2) years) and their parents (83% female; mean (SD) age=46.5 (5.1) years) were randomised to IERITA plus TAU (n=84) or TAU-only (n=82). IERITA is a 12-week, therapist-guided emotion regulation behavioural therapy, including both adolescents and parents. In parallel to the adolescent, parents participate in a separate internet-delivered course designed to provide skills for understanding and supporting their adolescent. The outcomes were parental coping measured by the Coping with Children’s Negative Emotions Scale-Adolescent version, including minimisation (primary outcome), distress, punitive and expressive encouragement responses at baseline, post-treatment (primary endpoint) and 3 months post-treatment. Parental minimisation was tested as a mediator of adolescent NSSI absence and emotion regulation difficulties. Findings There were statistically significant treatment effects on parental minimisation and distress responses at post-treatment and 3 months post-treatment, and punitive responses at 3 months post-treatment, favouring IERITA. Parental minimisation did not mediate adolescent NSSI absence or emotion regulation difficulties. Conclusion IERITA shows promise for supporting parents of youth with NSSI. Further studies are needed to understand how parental improvement may impact youth with NSSI. Clinical implications Online family treatment for NSSI can improve how parents handle their adolescents’ emotions. Trial registration number NCT03353961.
          Ojala, O., Sjöblom, K., Hesser, H., Hedman-Lagerlöf, E., Hellner, C., Bjureberg, J.
        • Medication use in severe anorexia nervosa: a Danish register-based study
          Background Severe anorexia nervosa (AN) represents a subgroup of individuals with AN with prolonged illness duration and poor prognosis. Previous research has reported increased medication use in AN, but prescription patterns in severe AN remain unexplored. Objectives This study aimed to: (1) compare medication prescriptions between individuals with severe and less-severe AN; (2) explore the heterogeneity of prescription patterns among individuals with severe AN across different comorbidity profiles. Methods Using Danish registers, this cohort study included 7654 individuals diagnosed with AN. We assigned cases to severe or less-severe groups based on their AN Register-based Severity Index scores. First, we examined trajectories of medication prescriptions and compared patterns between groups using logistic regression models. Second, common comorbidity profiles among individuals with severe AN were identified by latent class analysis for further between-group comparisons. Sensitivity analyses were conducted to test alternative definitions of severe AN. Findings Compared with individuals with less-severe AN, those with severe AN were more likely to be prescribed various medications, including drugs targeting alimentary tract (OR 1.4, 95% CI 1.3 to 1.6), cardiovascular drugs (OR 1.1, 95% CI 1.0 to 1.3), analgesics (OR 1.2, 95% CI 1.1 to 1.3) and psychotropic drugs (OR 2.4, 95% CI 2.1 to 2.7). Notably, this pattern persisted even among individuals without diagnosed comorbidities. Within the severe group, five clusters with distinct comorbidity profiles emerged, and we consistently observed greater prescription rates than in the comorbidity-free cluster. Sensitivity analyses confirmed that our severity classification reliably distinguished severe from less-severe AN across multiple definitions. Conclusion These findings indicate that severe AN is associated with substantially higher prevalence of prescribed medications, while specific comorbidity patterns further influence prescribing patterns. This diverse and prolonged pharmacological treatment in severe AN reflects the complexity of clinical management in this population. Clinical implications Considering the widespread medication prescription in severe AN despite the lack of specific approved pharmacotherapy for the disorder, evidence-based treatment guidelines are urgently needed. Clinicians should recognise the substantial heterogeneity in severity and comorbidity burden within this population and develop comprehensive and specialised treatment strategies that evaluate risks and treatment needs across all individuals with AN, irrespective of comorbid conditions.
          Zhang, Z.-P., Chatwin, H., Larsen, J. T., Clausen, L., Agerbo, E., Munk-Olsen, T., Bang Madsen, K., Vilhjalmsson, B. J., Petersen, L. V., Yilmaz, Z.
        • Identifying postpartum depression subtypes using natural language processing and clinical notes
          Background Postpartum depression (PPD) remains vastly underdiagnosed, and its clinical heterogeneity is not well understood. Diagnosis codes in electronic health records (EHRs) alone may not identify all PPD cases, highlighting a need for novel detection approaches. Objective To develop a transformer-based natural language processing (NLP) method to identify patients with PPD from clinical notes in EHRs and to examine demographic and clinical heterogeneity among identified cases. Methods Clinical notes from 64 426 patients who gave birth between 2010 and 2023 at a major US academic medical centre were used to develop and evaluate the NLP method. By augmenting the NLP output with International Classification of Diseases (ICD-9/10) diagnosis codes, three subgroups of individuals with PPD were identified: patients identified by ICD only (PPD-ICD), NLP only (PPD-NLP) and both ICD and NLP (PPD-BOTH). Demographics, mental health and substance use disorders (SUDs), antidepressant treatment, behavioural therapy and healthcare utilisation were compared across PPD subgroups and a non-PPD control group. Longitudinal associations of depression and anxiety were also examined. Findings The NLP method identified an additional 29.6% of patients whose clinical notes indicated symptoms suggestive of PPD but who lacked an ICD diagnosis. Significant variation was observed among PPD subgroups in comorbid psychiatric disorders, SUDs, treatment patterns and healthcare utilisation. During the 24 months post-delivery, the PPD-BOTH subgroup exhibited the highest rates of anxiety disorder diagnoses (vs PPD-ICD: OR 1.69, 95% CI 1.49 to 1.93; vs PPD-NLP: OR 4.46, 95% CI 3.82 to 5.22), antidepressant prescriptions (vs PPD-ICD: OR 1.95, 95% CI 1.71 to 2.22; vs PPD-NLP: OR 5.98, 95% CI 5.11 to 7.01) and mental health outpatient visits (vs PPD-ICD: OR 1.45, 95% CI 1.24 to 1.7; vs PPD-NLP: OR 4.94, 95% CI 3.9 to 6.31), suggesting higher symptom severity (all p<0.001). Comorbid depression and anxiety diagnoses were most prevalent during the postpartum period and declined over time. Conclusions Augmenting NLP-based identification with ICD codes yielded more individuals with distinct demographic and clinical profiles, demonstrating the method’s ability to improve case detection and characterise heterogeneity. Clinical implications Given that PPD is underdiagnosed and undertreated, this novel approach demonstrates further potential for NLP in healthcare settings to capture more cases, enabling earlier and more personalised interventions that reach patients who may otherwise be overlooked.
          Adekkanattu, P., Vekaria, V., Zhang, Y., Patra, B. G., Liang, P., Sharko, M., Benda, N., Reading Turchioe, M., Temkin-Yu, A., Hermann, A., Pathak, J.
        • Sex differences in familial risk and genetic components of suicide attempts: a register-based cohort study in Sweden
          Background Suicidal behaviour shows notable sex differences, and understanding whether genetic factors contribute to these differences is critical for identifying at-risk individuals and prevention. Objective We aim to investigate the genetic contribution to suicide attempts and examine whether genetics account for sex differences in incidence. Methods This population-based cohort study includes 3.1 million individuals born 1963–1998 and followed through Swedish National Registers, including hospitals and specialist outpatient diagnoses and cause of death data. Suicide attempts were identified using ICD codes, indicating intentional self-harm, self-harm using lethal methods or leading to hospitalisation, or resulting in death. Familial aggregation, coaggregation, pedigree heritability and genetic correlations were estimated using genealogical data. For sex-specific analyses, we examined mother–daughter, female sibling, father–son and male sibling pairs, separately. Findings Suicide attempts were more common among females than males (3.3% vs 2.6%). In both sexes, risk aggregated within families (ORs ranged 1.6–3.4 across relative types) and was higher in first-degree than second-degree relatives. Familial aggregation was stronger in females than in males, and in same-sex first degree relatives compared with cross-sex pairs. Pedigree heritability was 41.9% (95% CI 36.0 to 48.4%) and did not differ significantly by sex (female 51.4% (95% CI 40.1% to 58.6%), male 45.1% (95% CI 32.3% to 52.5%), Bootstrap p value 0.40). Suicide attempt showed moderate to high pedigree genetic correlations with psychiatric disorders, strongest with substance use disorders (SUD, rg=0.85 (95% CI 0.83 to 0.96)), with no significant sex differences. The genetic correlation between female and male suicide attempts was high (0.85 (95% CI 0.80 to 0.99)), suggesting a substantial genetic overlap. Conclusions Suicide attempt has a moderate heritable component that largely overlaps between females and males and with other psychiatric disorders, particularly SUD. Stronger familial aggregation in females and in same-sex pairs highlights the potential role of sex-specific environmental or social factors. Future research should focus on non-genetic contributors and their potential interaction with genetic factors to better understand and address sex disparities in suicidal behaviour Clinical implications Genetic risk for suicide attempt is substantial but does not fully explain sex differences in incidence. Clinicians should, therefore, consider non-genetic, including sex-specific environmental and social factors, alongside family history and psychiatric comorbidity when assessing suicidal risk.
          Nguyen, T.-D., Gong, T., Hu, K., Kuja-Halkola, R., Borges, K., Butwicka, A., Brikell, I., Crowley, J. J., Chang, Z., DOnofrio, B. M., Larsson, H., Lichtenstein, P., Rück, C., Bulik, C., Fang, F., Sullivan, P., Lu, Y.
        • Research priorities for mental health and circadian science: a priority setting partnership of individuals with lived experience, carers, clinicians and researchers
          Background Undisturbed circadian rhythms of rest/activity are crucial to health and well-being. There is growing evidence to suggest that circadian rhythm disruptions are also associated with adverse mental health outcomes (and vice versa), but important questions about the relationship between circadian rhythms and mental health remain unanswered. Objective To determine future priorities for research in the area of mental health and circadian rhythms, a James Lind Alliance Priority Setting Partnership exercise in collaboration with a steering group comprising individuals with lived experience, carers and clinicians was undertaken. Methods An initial survey among UK residents provided a set of 964 questions supplied by 247 respondents (227 lived experience, 44 carers (including 40 carers with lived experience), 41 clinicians (including 37 clinicians with lived experience)). Responses were processed into 171 summary questions by the steering group. Reviews of published research and existing clinical guidelines reduced this to 63 unanswered summary questions. A ranking survey of these 63 questions asked respondents to select their 10 most important research questions, from which the most highly ranked would be taken to the final stage. This was completed by 222 respondents (200 lived experience, 33 carers (including 29 carers with lived experience), 38 clinicians (including 30 clinicians with lived experience)). Findings In a final face-to-face workshop, 19 individuals, including individuals with lived experience, carers and clinicians, discussed and ranked a list of questions to produce a ranking of the top 25 research questions/priorities, with a particular focus on the Top 10. Discussion The final research questions are presented to inform researchers and funding bodies when setting future research priorities across the fields of mental health and circadian rhythms. Clinical implications Addressing the priorities identified here should lead to greater understanding of the relationships between mental health and circadian rhythms and will have longer-term impacts on research, healthcare innovation and public health policy.
          Ferguson, A. C., Kamenska, I., Ahmad, N., Needham, N., Farquhar, M., Stephens, C., Abid, U., Perry, D., Gardani, M., Meyer, N., Deeb, H., Marwick, K. F. M., Smith, D. J., von Schantz, M., Gregory, A. M.
        • Risk of neutropenia-related hospitalisation among clozapine initiators
          Background Clozapine is highly effective for treatment-resistant schizophrenia but has been associated with an increased risk of agranulocytosis. As a result, until 2025, the Food and Drug Administration required patients receiving clozapine to undergo regular blood testing to monitor for neutropenia as part of a Risk Evaluation and Mitigation Strategy (REMS) programme. Objective This study sought to compare the risk of neutropenia-related hospitalisations between clozapine and olanzapine initiators. Methods The study cohort was nested in claims data from Medicaid and two commercial health insurance databases and consisted of adults initiating clozapine or olanzapine who had a recorded diagnosis of schizophrenia or schizoaffective disorder and ≥1 dispensing of a different antipsychotic in the 6 months before initiation. Propensity score matching (1:1) was used to mitigate confounding. The primary outcome was hospitalisation with a neutropenia diagnosis in the primary position. Both as-treated and intention-to-treat analyses were implemented. Findings After propensity score matching, there were 16 873 initiators in each group. At 6 months postinitiation, there were 12 neutropenia-related hospitalisations among the clozapine cohort (incidence rate: 2.21 per 1000 person-years; 95% CI 1.25 to 3.89) and <11 among the olanzapine cohort (0.18; 95% CI 0.03 to 1.29), corresponding to an incidence rate ratio (IRR) of 12.18 (95% CI 1.58 to 93.71). The IRRs were 5.77 (95% CI 1.29 to 25.76) at 1 year, 5.50 (95% CI 1.23 to 24.55) at 2 years and 5.40 (95% CI 1.21 to 24.13) at 3 years postinitiation. Associations remained but were attenuated in intention-to-treat analyses. Conclusions Clozapine initiators had an elevated risk of neutropenia-related hospitalisation, especially during the first 6 months of treatment, although the absolute risk was low. Clinical implications Despite removal of the REMS programme, it is important for prescribers to monitor patients for neutropenia after initiating clozapine.
          Sarpatwari, A., Mahesri, M., Lii, J., Lee, S. B., Zakoul, H., Toyserkani, G. A., Zhou, E. H., Lacivita, C., Dal Pan, G. J., Bykov, K., Moran, L., Avorn, J., Kesselheim, A. S., Huybrechts, K. F.
        • Discontinuation and reinitiation of pharmacological treatment for ADHD among individuals with ADHD and substance use disorder
          Background Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) often coexist. ADHD complicates the course of disease in SUD. While recommended in guidelines, ADHD medication for those with comorbid SUD remains controversial. Objective This study aims to explore how comorbid SUD affects ADHD medication discontinuation and reinitiation in individuals with ADHD. Methods Using a matched cohort design, we identified 9283 individuals with ADHD and SUD in Sweden between 2006 and 2020, who had ongoing ADHD medication at the time of their first SUD-related event. Controls with ADHD medication but no SUD (n=46 401) were matched 5:1 on sex and birth year. HRs for treatment discontinuation within 1 year from first SUD, and for treatment reinitiation within 1 year from the first discontinuation, were estimated using stratified Cox models. Findings Individuals with ADHD and SUD were nearly two times as likely to discontinue ADHD treatment within 1 year (HR: 1.99, 95% CI 1.92 to 2.07) and less likely to re-initiate ADHD treatment (HR: 0.82, 95% CI 0.76 to 0.89) compared with controls. Several factors, including male sex, adolescent to young adult age and lower stimulant medication dose, were associated with increased risk for treatment discontinuation, but only adolescent to young adult age was significantly associated with treatment reinitiation in those with ADHD and SUD. Conclusions The results suggest less treatment continuity and access for those with ADHD and comorbid SUD. Clinical implications Treatment providers need to consider the specific needs of individuals with ADHD and comorbid SUD, especially in young males, to improve treatment outcomes for vulnerable groups.
          Capusan, A. J., Zhang, L., Larsson, H., Brikell, I., Martinez, D., DOnofrio, B. M., Lichtenstein, P., Kuja-Halkola, R., Chang, Z.
        • Reduced risk of cause-specific hospitalisations and all-cause hospitalisation/mortality during treatment with attention-deficit/hyperactivity disorder medications in the course of bipolar disorder: a Swedish registry-based within-subject cohort study
          Background Comorbid attention-deficit/hyperactivity disorder (ADHD) increases the burden in bipolar disorder (BD). Concerns about the risk/benefit balance of ADHD treatment have been raised. Objective This study aimed to investigate the association between hospital admissions and add-on ADHD medications to antipsychotics and/or mood-stabilisers (APs/MSs) compared with AP/MS alone in BD. Methods Individuals with BD prescribed ADHD medications in Sweden during 2006–2021 were identified from national registers of inpatient care, specialised outpatient care, sickness absence and disability pension. ADHD treatment was defined as stimulants (mostly methylphenidate and lisdexamfetamine, rarely amphetamine, dexamphetamine) and non-stimulants (atomoxetine, modafinil). Add-on ADHD treatment to concomitant AP/MS was compared with treatment periods with AP/MS without ADHD treatment, using within-individual models where individuals acted as their own control. Adjusted HRs (aHRs) and CIs (95% CIs) were calculated for the primary outcome of psychiatric hospitalisation, and for the secondary outcomes: substance-use-related, somatic or mania-related hospitalisations, and all-cause hospitalisation/mortality. Results Altogether, 17 971 individuals (mean age=32.0±11.6 years, males=37.6%, ADHD=88.9%, follow-up=8.9±4.4 years) with BD who used any ADHD treatment were included. compared with the use of AP/MS alone, add-on stimulant use was related to a lower risk of psychiatric hospitalisations (aHR=0.89, 95% CI 0.85 to 0.93), substance-related hospitalisations (aHR=0.75, 95% CI 0.70 to 0.81) and all-cause hospitalisations/mortality (aHR=0.90, 95% CI 0.87 to 0.93), but was not associated with increased risk for somatic (aHR=1.00, 95% CI 0.90 to 1.12) or mania-related hospitalisations (aHR=0.93, 95% CI 0.72 to 1.20). Of commonly used specific ADHD medications, add-on lisdexamfetamine (aHR=0.81, 95% CI 0.75 to 0.87) and methylphenidate (aHR=0.92, 95% CI 0.88 to 0.97) were associated with decreased risk of psychiatric hospitalisations while add-on atomoxetine was not. Findings on substance-use-related hospitalisations were significant only for stimulants, specifically lisdexamfetamine (aHR=0.70, 95% CI 0.61 to 0.79) and methylphenidate (aHR=0.80, 95% CI 0.74 to 0.86). Conclusions Among individuals with BD who received ADHD medications, add-on lisdexamfetamine and methylphenidate were associated with lower risks of psychiatric and substance-use-related hospital admissions, compared with AP/MS use alone. No significant association was found between ADHD medication use and mania-related hospitalisations or somatic admissions when these medications were used together with AP/MS. Larger samples are needed to reach adequate statistical power and conclusive findings on atomoxetine, dexamfetamine and modafinil. Clinical implications The findings of this study suggested that the treatment of comorbid ADHD could be considered after adequate mood-stabilisation in patients with BD.
          Ermis, C., Tanskanen, A., Corbeil, O., Lieslehto, J., Vieta, E., Correll, C. U., Mittendorfer-Rutz, E., Tiihonen, J., Taipale, H.
        • Metabolomic ageing across mental and behavioural disorders
          Background Individuals with mental disorders face excess morbidity and premature mortality. Accelerated ageing has been proposed as a contributing mechanism but population-scale evidence across diverse diagnoses is limited. Objective To examine whether metabolomic ageing differs across mental disorders and whether associations vary by sex, age group and genetic liability. Methods Using plasma metabolomic profiles from UK Biobank participants, we applied a metabolomic ageing clock (MileAge) to estimate disorder-specific differences between metabolite-predicted and chronological age. Mental disorders were ascertained from health records and self-reported physician diagnoses. We analysed nine diagnostic groups and 45 individual disorders and assessed sex and age group differences and associations with polygenic scores. Findings Among 225 212 participants (54% female; mean age 56.97), 38 524 had a diagnosis preceding baseline. Substance use, psychotic, affective and neurotic disorders were associated with a metabolite-predicted age older than chronological age, largest for psychosis (β=0.556, 95% CI 0.250 to 0.861, p<0.001). Obsessive-compulsive and eating disorders were associated with a metabolite-predicted age younger than chronological age. Several associations were stronger in males and in individuals aged <65 years. Higher genetic liability to depression, autism and attention-deficit/hyperactivity disorder predicted an older metabolomic age (β range=0.020 to 0.047), whereas polygenic scores for psychosis and tobacco use disorder predicted a younger metabolomic age (β range=–0.023 to –0.040). For obsessive-compulsive disorder and anorexia nervosa, clinical and genetic associations indicated younger metabolomic ageing. Conclusions Metabolomic ageing in mental disorders is heterogeneous. While many disorders are associated with an older biological age, some are linked to a younger biological age. Divergence between genetic liability and clinical phenotypes suggests that non-genetic factors shape biological ageing differences. Clinical implications Biological age should not be assumed to uniformly exceed chronological age across mental disorders. Sex and age-specific approaches could improve understanding of biological ageing processes in psychiatry.
          Mutz, J., Gilchrist, L., Allegrini, A. G., Sanchez Roige, S., Lewis, C. M.
        • Levels of evidence supporting American, European and international guidelines in psychiatry, 2014-2024: a systematic review with quantitative synthesis
          Question To what extent are psychiatry guidelines supported by high-level evidence? Study selection and analysis Guidelines from the American Psychiatric Association, European Psychiatric Association, WHO and World Federation of Societies for Biological Psychiatry (2014–2024) were selected. Recommendations were graded by guideline authors’ levels of evidence (LOE) appraisal (standardised to the Grading of Recommendations, Assessment, Development and Evaluations framework (high, moderate, low, very low)) and by the highest-level study referenced (meta-analysis, randomised controlled trial (RCT), observational study, expert opinion, etc.). Findings 24 guidelines, containing 545 recommendations, were included. Of 82 guidelines screened, 29 (35%) had not been updated in a decade. 63 (11.6%) recommendations were rated by guideline authors as based on high LOE. The proportion was the highest for pharmacotherapies (41/281 (14.6%)) and the lowest for somatic assessment (0/13 (0%)). The proportion of high LOE recommendations varied between publishers (European Psychiatric Association: 20 %, WHO: 1.6 %). For high LOE recommendations, only those concerning pharmacotherapies cited meta-analyses based on double-blind studies using adequate controls. A large proportion (n=241 (44.2%)) of recommendations cited either a meta-analysis of RCTs (n=155 (28.4%)) or ≥two RCTs (n=86 (15.8 %)). There were few recommendations primarily addressing self-harm (n=2), autism (n=3), attention-deficit/hyperactivity disorder (n=3), prevention (n=3), patient involvement (n=3) or discontinuation (n=6). Conclusions Clinical guidelines in psychiatry frequently cite RCTs, but the evidence is often downgraded by guideline authors, highlighting the need for better quality trials. LOE varies across areas, with pharmacotherapies supported by the highest quality evidence. Organisations should commit to a timely update of guidelines covering all areas of psychiatry.
          Romer, T. B., Andersson, S. N., Benros, M. E.
        • Effects of a mindfulness-based intervention versus a social contact control in alleviating loneliness among older adults: a randomised controlled trial
          Background Loneliness is highly prevalent among Chinese older adults. Mindfulness-based interventions for older adults (MBOA) have demonstrated potential in alleviating loneliness. However, few studies have employed active controls with long-term follow-up. Objective This study aimed to assess the efficacy of MBOA in reducing loneliness compared with social contact control (SCC). Methods This parallel, randomised controlled trial (RCT) assigned community-dwelling lonely Chinese older adults (≥60 years) in Hong Kong to MBOA or SCC. Both interventions comprised 8 weekly 1.5-hour group-based face-to-face sessions. Assessments were conducted at baseline, postintervention and at 6-month and 12-month postrandomisation. The primary outcome was loneliness score at 12 months, analysed using analysis of covariance under the intention-to-treat approach. Secondary outcomes included depression, anxiety, health-related quality of life and healthcare utilisation. Changes in psychological measures were analysed using linear mixed models. Findings A total of 245 eligible participants were randomised to MBOA (n=123) or SCC (n=122). No significant between-group difference in primary outcome was found (mean difference=–0.14, p=0.52, effect size=–0.21), although both groups showed improvement in loneliness (within-group effect size: MBOA=–0.58, SCC=–0.31). MBOA participants reported reduced depressive symptoms and a decreasing trend in anxiety at 6 months compared with SCC. Conclusion This is the first RCT examining efficacy of MBOA in alleviating loneliness among Chinese older adults using an active control with long-term assessments. MBOA is not superior to SCC in reducing loneliness, although it may reduce psychological symptoms. Clinical implication Clinicians could consider prioritising mindfulness-based interventions for lonely older adults when depressive or anxiety symptoms are prominent.
          Wong, E. T.-F., Lee, E. K.-P., Mo, P. K.-H., Xu, Z., Zhang, D., Woo, J., Kwok, T. C.-Y., Lee, T. M.-C., Lo, H. H.-M., Liu, D. Y.-W., Ngai, C. H., Chan, D. C.-C., Mercer, S. W., Yip, B. H.-K., Wong, S. Y.-S.
        • Are all risks equal? Understanding the differential mechanism linking early environmental risk and obesity via the interplay of mental health and lifestyle factors
          Background The mechanisms linking early environmental risk (EER) and obesity via the interplay of mental health and lifestyle factors in the early life stage remain unclear. Objective To examine whether EER was associated with later mental health, lifestyle factors and obesity and to identify the mediating roles of mental health and lifestyle in these relationships. Method Using data from the Millennium Cohort Study (valid n=5401), we longitudinally assessed the relationship between EER (prenatal risks, neonatal risks, low socioeconomic status, maternal psychological problems and harsh parenting; 9 months to age 3 years), mental health problems in childhood (internalising and externalising problems; age 7 years), lifestyle factors in early adolescence (diet, exercise, smoking and drinking; age 11 years) and obesity in late adolescence (age 14–17 years). Structural equation modelling was used to test proposed pathways. Findings The proposed model showed an acceptable fit (Comparative Fit Index=0.926, Tucker-Lewis Index=0.875, root mean square error of approximation=0.034, standardised root mean square residual=0.046). EER was significantly associated with later mental health problems, lifestyle factors (ie, diet, exercise, smoking) and obesity. Higher EER was modestly associated with higher obesity risk via the interplay of externalising problems and drinking (β=0.01, p=0.036). The sex-stratified model results indicated differences between males and females. Conclusion By highlighting the importance of EER and the mediating role of lifestyle factors in mental health and later obesity risk, our findings provide evidence of shared risk mechanisms linking mental and physical health. Clinical implications These findings suggest that integrating mental health assessment (especially externalising symptoms) with routine screening for adolescent alcohol use and other risk factors could inform more targeted obesity prevention in clinical and public health settings.
          Sun, H., Kiri, J., Brandt, V., Golm, D.
        • Automating thematic review of prevention of future deaths reports: concordance study of a child-suicide analysis using large language models
          Background Prevention of future deaths (PFD) reports issued by coroners in England and Wales identify systemic safety hazards but are difficult to analyse at scale. Reports are not machine-readable, lack consistent metadata and cannot be reliably searched or exported, meaning prior national reviews have relied on labour-intensive manual screening and coding. Objective To evaluate whether a fully automated, vision-enabled large language model (LLM) pipeline (PFD Toolkit) can replicate and extend the Office for National Statistics (ONS) thematic review of child-suicide PFD reports, and to assess concordance with blinded clinical adjudication. Methods All PFD reports published between July 2013 and November 2023 (n=4730) were scraped from judiciary.uk and processed using PFD Toolkit, which combines optical character recognition with LLM-powered screening and thematic coding. Reports were classified for child suicide (≤18 years), addressee categories and 23 coroner-concern subthemes mirroring the ONS coding frame. Agreement was evaluated against a blinded clinical reference standard: three psychiatrists independently adjudicated a stratified sample of 146 reports (73 Toolkit-positive cases and 73 decoys), with disagreements resolved by consensus. Inter-rater reliability and index-reference agreement were quantified using kappa statistics. Findings The Toolkit identified 73 child-suicide PFD reports between July 2013 and November 2023, compared with 37 identified in the ONS review. 62 cases fell within the ONS analytical window, and 11 pre-dated the introduction of suicide-related tags on the PFD archive. Pre-consensus inter-rater reliability among clinicians was substantial to almost perfect (Fleiss’ =0.75, 95% CI 0.65 to 0.84). Post-consensus agreement between the Toolkit and the clinical reference standard was substantial to almost perfect (Cohen’s =0.93, 95% CI 0.77 to 1.00; raw agreement 97%). End-to-end screening, coding and tabulation of all reports completed in 5 min 29 s on a consumer-grade laptop. Conclusions A national thematic review of child-suicide PFD reports can be fully automated with high concordance to expert judgement, dramatically reducing time and labour while recovering previously missed cases. Clinical implications Automated analysis of PFD reports enables rapid, reproducible surveillance of recurring system failures, supporting more timely public health intelligence, policy responses and learning from coronial data.
          Osian, S., Dutta, A., Bhandari, S., Buchan, I. E., Joyce, D. W.
        • Factors associated with the mental health of parents during and after their childs hospitalisation: an international longitudinal prospective cohort study
          Background A child’s hospitalisation may have long-term influences on parental mental health, which can affect child health. Objective To describe the prevalence of and examine factors associated with parents’ depression and anxiety symptoms over time. Methods This prospective cohort study in 14 countries measured parent mental health during their child’s hospitalisation, at discharge and 3 months postdischarge (2023–2024). We included parents ≥18 years staying at a Ronald McDonald House® during their child’s hospitalisation. Exposures were parent, family and child psychosocial and health factors and hospital experiences. Outcomes were parental depression and anxiety symptoms. We used mixed-effects logistic regression. Findings 3350 parents, including 2594 (78.6%) mothers, 616 (18.1%) fathers and 131 (3.3%) other caregivers, participated during hospitalisation; 1751 (52%) at discharge, and 2395 (71%) postdischarge. Prevalence of depression and anxiety symptoms was high during hospitalisation (49.7% and 69.0%, respectively) and decreased modestly at discharge (44.6% and 59.5%, respectively), and postdischarge (42.8% and 59.2%, respectively). Over time, probabilities of depression symptoms decreased among those with high, moderate and low levels of social support (50%, 27%, 5%, respectively), and self-care (29%, 27% and 22%, respectively). Probabilities of depression symptoms decreased among those with high or moderate perceived levels of family-centred care (high: 20% decrease; moderate: 11% decrease, compared with low). In contrast, probabilities of depression symptoms increased among those with high or moderate levels of unmet basic needs (high: 18% increase; moderate: 8% increase, compared with low) and poorer ratings of their child’s health (high: 68% increase; moderate: 32% increase, compared with low (healthier)). These trends were similar for anxiety symptoms. Conclusions Prevalence of depression and anxiety symptoms is high among parents and only decreases modestly postdischarge. Clinical implications Routine screening and ongoing services may lower the risk of prolonged parental mental health symptoms, but more research is needed.
          Mehra, R., Hoffmann, T. J., Graham-Squire, D., Lisanti, A. J., Gay, C., Hodgson, C., Rienks, J., Pavlik, M., Manju, S., Turaga, N., Clay, M., Franck, L. S.
        • Is it time for mental health services to invest in neurostimulation? An economic evaluation of transcranial magnetic stimulation therapies for the treatment of moderate to severe treatment-resistant depression in the UK
          Background Although transcranial magnetic stimulation (TMS) protocols are safe and efficacious therapies for treatment-resistant depression (TRD), they remain inaccessible for many people in the UK and internationally. One of the main reasons for this is a lack of evidence demonstrating their value-for-money to commissioners. Objective To assess the cost-effectiveness of repetitive transcranial magnetic stimulation therapy (rTMS) and intermittent theta-burst stimulation (iTBS) versus treatment-as-usual (TAU) for treating TRD in UK mental health care services, and to evaluate operational circumstances underpinning cost-effectiveness. Methods This economic evaluation used data from the BRIGHTMIND trial (n=255), the SMD trial (n=187) and a study-specific structured expert elicitation exercise (n=7) to model the cost and consequences for each alternative. All findings were produced on a probabilistic basis from a Markov model using Monte Carlo simulation methods. Cost-effectiveness was assessed via incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained over an 18-month time horizon from the perspectives of the UK’s NHS and personal social services and from a broader societal perspective recognisant of informal care hours and productivity costs. Scenario analyses and an operational sensitivity analysis explored the impacts alternative methodologies, service delivery cases and perspectives had on base case findings. Findings From a health service perspective, rTMS and iTBS had pairwise ICERs of £12 093 and £12 959 per QALY compared to TAU, respectively. When incrementally compared, iTBS had an ICER of £16 621 versus rTMS. From a broader societal perspective, both rTMS and iTBS reduced informal care hours and were cost-saving compared with TAU. Study findings were particularly sensitive to service delivery, with the probability of being cost-effective ranging from 98% with high throughput and prompt delivery to approximately 4% with low throughput and prolonged delivery. Conclusions TMS therapies improve health, reduce informal care requirements, reduce health service utilisation and offset their costs when considered in terms of productivity losses to society. rTMS and iTBS are cost-effective and should be considered for wider clinical implementation provided they are delivered at sufficient scale and in a time-efficient manner. Clinical implications TMS can serve as a cost-effective alternative for treating moderate to severe depression after second-line treatment failure with non-psychological therapies.
          Cox, E., Ma, J., Roadevin, C., Morriss, R., James, M.
        • Effectiveness of the Common Elements Treatment Approach for mental and behavioural health outcomes among women struggling to remain adherent to HIV treatment and who have experienced intimate partner violence in South Africa: secondary outcomes from a randomised controlled trial
          Background Rates of intimate partner violence (IPV) and HIV in South Africa are among the highest globally. IPV is associated with a range of adverse mental health and HIV outcomes. The Common Elements Treatment Approach (CETA) is a transdiagnostic, evidence-based intervention delivered by lay providers. Objective To compare the effectiveness of CETA to active attention control in reducing IPV, depression, post-traumatic stress disorder (PTSD) and substance use among women at risk of poor HIV outcomes who have experienced IPV. Methods Women living with HIV with an unsuppressed viral load or at risk for poor adherence and experienced past 12-month IPV were recruited from Johannesburg-area clinics and randomised 1:1 to CETA or control (SMS HIV appointment reminders plus safety checks and planning). The primary trial outcome was HIV retention and viral suppression, under review elsewhere. This paper reports secondary outcomes, evaluated at 3 and 12 months: IPV, depression, PTSD and substance use. Findings Participants were enrolled between 11 November 2021 and 19 July 2023 and randomised to CETA (N=202) or control (N=197). In the intent to treat analysis, the Cohen’s d treatment effect for depression at 3 months was 0.24 (difference in mean change –3.1; 95% CI –6.1 to 0.1) and 0.48 at 12 months (–6.2; 95% CI –9.5 to –2.8). The PTSD treatment effect was 0.39 at 3 (–0.3; 95% CI –0.5 to –0.1) and 0.47 at 12 months (–0.3; 95% CI –0.5 to –0.2). Effect sizes were larger in a subgroup of participants with the top 50% of baseline symptom scores (depression: d=0.50, d=0.74; PTSD: d=0.58, d=0.94, at 3 and 12 months, respectively). There were no statistically significant differences in change for substance use or IPV. At baseline, only 12% of participants had past 3-month substance use and 32% had past 3-month or ongoing experiences of IPV, which made these outcomes challenging to evaluate. Conclusions CETA was effective for reducing depression and PTSD, including among high severity participants and at an extended follow-up. Future studies with increased power for substance use and IPV outcomes are warranted. Clinical implications CETA is a recommended treatment for depression and PTSD among this population. Trial registration number NCT04242992.
          Zheng, A., Kane, J. C., Mngadi-Ncube, S., Fox, M. P., Manganye, P., Long, L., Metz, K., Sardana, S., Alto, M., Greener, R., Thea, D. M., Murray, L. K., Pascoe, S.
        • Congenital malformation risk following prenatal antipsychotic exposure: a systematic safety surveillance approach
          Background Medication safety studies in pregnancy typically focus on selected or composite outcomes (eg, any malformation) to test specific hypotheses or verify suspected safety signals, potentially overlooking or masking other clinically significant associations (eg, individual malformations or malformation types). Objective To conduct a comprehensive, systematic screening for potential teratogenic safety alerts associated with first-trimester exposure to individual antipsychotics, using a tree-based scan statistic (TBSS) approach for simultaneous evaluation of a broad range of specific malformations and malformation groupings. Methods Using a US-nationwide cohort of >4.2 million mother–child dyads (2000–2020), pregnancies with ≥1 first-trimester antipsychotic dispensing were compared with antipsychotic-unexposed pregnancies. Individual congenital malformations were identified via International Classification of Diseases codes, grouped into increasingly aggregated higher-level clinically related categories. Leveraging this hierarchical classification tree, TBSS was used to scan for associations with individual malformation codes and code categories while tightly controlling type 1 error. Confounding was adjusted for via propensity score fine-stratification, and relative risks (RRs) were estimated using an unconditional Poisson scan statistic. The p-values were used to prioritise alerts for further investigation, and follow-up analyses were conducted to refine the understanding of statistical alerts. Findings Exposed pregnancies ranged from 68 (fluphenazine) to 18 366 (prochlorperazine). Antipsychotic-exposed versus antipsychotic-unexposed women tended to be older and to have a higher comorbidity burden and more healthcare encounters. Alerts for an increased risk (with p<0.1) were observed for skin anomaly after haloperidol (RR=1.88) and polydactyly after ziprasidone (RR=3.06) exposure. Results were consistent in sensitivity analyses. The data in the two external data sources were too sparse to confirm a safety alert. Conclusions TBSS identified two potential alerts previously unreported for prenatal antipsychotic exposure. Importantly, no alerts for severe or life-threatening malformations were detected. Findings from this screening-based approach, therefore, align with existing evidence suggesting that antipsychotics are unlikely to be major teratogens. Clinical implications The potential risk increase observed for some less-severe malformations and some antipsychotics needs to be weighed against the high potential for relapse and mental health deterioration following treatment discontinuation. While no consistent patterns suggesting a strong teratogenic effect have emerged thus far for newer antipsychotics, continued monitoring of these medications is important.
          Straub, L., Wang, S. V., Hernandez-Diaz, S., Bateman, B. T., Vine, S. M., Russo, M., Zhu, Y., Cohen, L., Cesta, C. E., Gray, K. J., Huybrechts, K. F.
        • Digital peer support interventions for people with mental health conditions in outpatient settings: a systematic review and meta-analysis
          Background Mental health conditions are a major global challenge with rising demand for accessible, effective, scalable treatments. Digital peer support interventions are a promising way to extend support beyond clinical settings, but their effectiveness requires comprehensive evaluation. Objective To evaluate the effectiveness of digital peer support interventions in improving clinical symptoms, functioning, and treatment engagement among individuals with mental health conditions in outpatient settings. Study selection and analysis We conducted a systematic review and random-effects meta-analysis of controlled interventional studies. Five databases (MEDLINE, CENTRAL, Embase, PsycINFO) were searched up to January 2025. Studies evaluated digital peer support via online platforms, mobile apps or digital communities for people aged ≥16 years with mental health conditions. Outcomes included clinical symptoms (depression, anxiety), functioning (quality of life, social functioning) and treatment engagement. Risk of bias was assessed using Cochrane Risk of Bias 2.0 for randomised controlled trials and ROBINS-I for non-randomised studies. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Findings 29 studies including 5825 participants were included. Digital peer support was associated with small-to-moderate improvements in symptoms of depression (standardised mean difference (SMD) –0.28; 95% CI –0.42 to –0.14) and anxiety (SMD –0.47; 95% CI –0.68 to –0.27). Functional outcomes improved modestly: social functioning (SMD 0.18; 95% CI 0.07 to 0.29), quality of life (SMD 0.14; 95% CI 0.02 to 0.26), patient activation (SMD 0.39; 95% CI 0.23 to 0.55) and personal recovery (SMD 0.23; 95% CI 0.11 to 0.35). No significant effects were observed for treatment engagement or satisfaction. Preliminary evidence suggested sustained benefits for depression, anxiety and social functioning. Conclusions and clinical implications Digital peer support offers modest improvements in symptoms and functioning for individuals with mental health conditions and may be considered as an adjunct to usual care to enhance engagement and provide accessible support between clinical contacts. Key priorities include establishing optimal intervention models, clarifying longer-term benefits, and ensuring these approaches can be delivered safely and sustainably within routine outpatient services. PROSPERO registration number CRD42023445194.
          Croke, S., Tyler, N., Low, C.-N., Gkintoni, E., Angelakis, I., Eylem-Van Bergeijk, O., Hodkinson, A., Mcmillan, B., Panagioti, M.
        • Postpartum self-harm thoughts and subsequent risk of intentional self-harm
          Objective Suicide is a leading cause of maternal mortality, with many cases considered preventable. The Edinburgh Postnatal Depression Scale (EPDS) item 10 screens for self-harm thoughts in the past 7 days. This study aimed to investigate whether a positive response (‘hardly ever’, ‘sometimes’ or ‘quite often’) is associated with subsequent hospital-registered intentional self-harm, non-suicidal or suicidal, among postpartum women. Methods We conducted a population-based cohort study of 170 218 childbirths (38% of the source population) from 142 795 unique women in Denmark by linking nationwide registers with the HOPE cohort. Self-harm thoughts were defined as any non-zero response to EPDS item 10. The primary outcome was a hospital-recorded episode of intentional self-harm within 365 days after childbirth. To account for confounding, we applied inverse propensity-score weighting, and we used Firth’s penalised logistic regression to estimate ORs. Results Of the 170 218 childbirths, 2935 (1.7%) reported self-harm thoughts. During a mean (SD) follow-up of 303.0 (11.2) days, eight women (0.27%) with self-harm thoughts were hospitalised due to intentional self-harm, demonstrating a 24-fold higher crude rate compared with women without self-harm thoughts (0.01%). After applying weighting, the adjusted OR remained significantly elevated at 10.91 (95% CI 7.03 to 17.99). Conclusion This is the largest study to date on this topic. We found that postpartum women reporting self-harm thoughts had a low absolute risk of intentional self-harm, but the relative risk was 11-fold higher. These results highlight the importance of further assessment and timely support for mothers identified as being at risk.
          Liu, X., Christiansen, E., Bergink, V., Kjeldsen, M.-M. Z., Maegbaek, M. L., Munk-Olsen, T.
        • Antidepressant use among American adults in a 50-state survey
          Background Antidepressants are among the most prescribed medications in the USA, yet challenges in access to mental health treatment persist. Objective To assess current and lifetime antidepressant and psychotherapy use among American adults, and examine attitudes towards potential federal restrictions on antidepressant prescribing. Methods We conducted a cross-sectional survey study using data from a national non-probability internet-based panel weighted to approximate national demographics (age, gender, race and ethnicity, education, US census region, and urbanicity) based on 2020 US Census data. Data were collected between 10 April and 27 May 2025 from 30 810 adults residing in the USA. The primary outcomes were self-reported current and past antidepressant and psychotherapy use, and support for or opposition to potential federal restrictions on antidepressant prescribing. Logistic regression models estimated demographic and treatment-related features associated with these outcomes. Findings Among 30 115 respondents with complete antidepressant data, 16.6% reported current antidepressant use, and of 30 098 respondents with psychotherapy data, 10.4% reported current psychotherapy. Use of both treatments was significantly greater among White respondents compared with all other racial groups. When asked about potential federal restrictions on doctors prescribing antidepressants, 16.4% of respondents supported and 48.0% opposed such regulation, with lesser opposition among those of male gender (OR 0.69, 95% CI 0.65 to 0.73), and greater opposition among those with lifetime antidepressant treatment (OR 2.37, 95% CI 2.21 to 2.54). Conclusions Antidepressant and psychotherapy use remains unevenly distributed across demographic groups. A significant proportion of adults in every US state oppose efforts to restrict access to antidepressant prescribing, reflecting broad public support for maintaining access to treatment. Clinical implications Findings from this study suggest that restrictive policies on antidepressant prescribing are unlikely to align with public sentiment and may risk exacerbating existing inequities in care.
          Perlis, R. H., Ramachandiran, A. K., Verhaak, P. F., Santillana, M., Baum, M. A., Druckman, J. N., Ognyanova, K., Lazer, D.
        • Cannabis use, cognitive function and dementia risk in older adults: observational and genetic analyses
          Background The cognitive effects of cannabis use in older adults remain unclear, despite increasing use for medical and recreational purposes in this age group. Objective To investigate associations between cannabis use, cognitive performance and dementia risk in older individuals, using large population cohorts and Mendelian randomisation (MR) to explore potential causal relationships. Methods Observational analyses were conducted using the UK Biobank (UKB) and the US Million Veteran Program (MVP). In UKB, cross-sectional and longitudinal cognitive performance across five domains was compared between lifetime cannabis users (up to 18 975 participants) and non-users (up to 60 598 participants). In MVP, cannabis use disorder (CanUD; n=12 222) was examined in relation to incident all-cause dementia using Cox proportional hazards models. MR analyses assessed potential bidirectional causal relationships between cannabis use, cognitive function and dementia. Findings At baseline, cannabis users performed modestly better on tests of numeric memory (beta=0.07, 95% CI 0.06 to 0.09, p<0.001) and fluid intelligence (beta=0.12, 95% CI 0.10 to 0.13, p<0.001), but no significant differences were observed in longitudinal cognitive change. In MVP, CanUD was not significantly associated with dementia risk (HR=1.11, 95% CI 0.97 to 1.26, p=0.12). MR analyses provided no evidence of a causal relationship between cannabis use and either cognitive performance or dementia risk. Conclusions Cannabis use was not linked to longitudinal cognitive decline or dementia risk. Within the limits of these cohorts, we found no evidence that cannabis use contributes substantially to cognitive ageing or dementia risk in older adults. Further research with detailed exposure assessment and longer follow-up is warranted to confirm these findings. Clinical implications Cannabis use in older adults does not appear linked to faster cognitive decline or higher dementia risk. Occasional or prior use may not substantially affect cognitive ageing, though safety at higher doses or prolonged use remains uncertain. Clinicians should inquire about cannabis history and consider cognitive screening in routine care.
          Ishrat, S., Levey, D. F., Gelernter, J., Ebmeier, K. P., Topiwala, A.
        • Effects of smartphone cognitive behavioural therapy on social functioning in non-depressive and subthreshold depressive adults: a secondary analysis of the RESiLIENT trial
          Background Depression is a leading cause of global disability, and subthreshold cases contribute substantially to the burden. Cognitive behavioural therapy (CBT) is effective for depressive symptoms, but its impact on social functioning in subthreshold depression remains unclear. Objective This study evaluated the effects of smartphone-based CBT on social functioning and personal health records among individuals with subthreshold depression and examined whether a personalised and optimised therapy (POT) algorithm enhanced these outcomes. Methods We performed a secondary analysis of the RESiLIENT trial (n=5361). Participants were stratified by baseline Patient Health Questionnaire-9 (PHQ-9) scores (0–4 and 5–14) and randomised to nine CBT app groups or a self-check group. Outcomes included social functioning and health records. A mixed-effects model for repeated measures was used to analyse the outcomes. The POT algorithm selected CBT skills tailored to individual characteristics. Findings Depressive symptoms improved in both PHQ-9 groups compared with those of the self-check group, but gains in social functioning were modest, observed mainly in the PHQ-9 score ≤4 group. No consistent benefits were seen for health behaviours, job resignation, sick leave or healthcare costs. However, in a simulated randomised comparison using 10-fold cross-validated datasets, the POT algorithm had potentially beneficial effects for productivity (standardised mean difference (SMD)=0.16, 95% CI 0.03 to 0.29) and social adjustment (SMD=–0.13, 95% CI –0.26 to 0.00). Conclusions Smartphone CBT effectively reduced depressive symptoms but showed limited impact on social functioning and healthcare costs. Personalised optimisation may modestly improve productivity and adjustment, suggesting its promise for enhancing social outcomes. Clinical implications Personalised tailoring of CBT skills may strengthen the effects of digital interventions on social functioning. Trial registration number UMIN000047124.
          Tajika, A., Toyomoto, R., Sakata, M., Luo, Y., Akechi, T., Horikoshi, M., Inoue, K., Noma, H., Cuijpers, P., Furukawa, T. A.
        • Mental health in university students: an umbrella review grading the evidence for psychosocial interventions
          Question Psychological distress is increasingly prevalent among university students, raising concerns about their mental health. This review aimed to assess the strength and credibility of evidence on the efficacy of psychosocial interventions for improving mental health in this population. Study selection and analysis We conducted an umbrella review of systematic reviews (SRs) with meta-analyses of randomised controlled trials assessing psychosocial interventions among university students. Searches were performed in Medline, PubMed, Cochrane Central, PsycINFO, CINAHL, Epistemonikos and Campbell Collaboration from 1 January 2014 to 1 February 2026. Data on intervention type, comparator, outcome and study-level effect sizes were analysed using inverse-variance random-effects models with restricted maximum likelihood estimation of between-study heterogeneity (²). Strength of associations was evaluated according to umbrella review criteria, reporting quality using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Findings A total of 34 SRs were identified. After excluding overlapping syntheses, 28 unique meta-analyses from 12 SRs were included. Mindfulness-based interventions versus inactive controls for distress (standardised mean difference (SMD) –0.40; 95% CI –0.53 to –0.28) showed highly suggestive evidence (class II; GRADE: low; AMSTAR: high). Seven associations provided suggestive evidence (Class III): mindfulness-based interventions versus inactive controls for anxiety (SMD –0.54; 95% CI –0.81 to –0.27) and depression (SMD –0.52; 95% CI –0.65 to –0.39); cognitive-based interventions versus inactive controls for anxiety (SMD –0.48; 95% CI –0.62 to –0.34) and depression (SMD –0.60; 95% CI –0.75 to –0.45); cognitive-based interventions versus active controls for well-being (SMD –0.30; 95% CI –0.42 to –0.18); positive psychology interventions versus inactive controls for distress (SMD –0.22; 95% CI –0.35 to –0.10); and multimodal interventions versus inactive controls for distress (SMD –0.85; 95% CI –1.32 to –0.87). The remaining associations were weak or non-significant, generally supported by low or very low certainty and mostly low or very low reporting quality. Conclusions The most robust evidence emerged for mindfulness and cognitive-based interventions, with some support also for positive psychology approaches. These interventions appear to improve depression, anxiety, distress and well-being among university students, though further rigorous research is needed. PROSPERO registration number CRD42023493618.
          Muriago, G., Chiccoli, A., Papola, D., Compri, B., Turrini, G., Nose, M., Barbui, C.
        • 'It is just a prediction; its, like, not fact: youth attitudes towards risk prediction tools and personalised preventive interventions for depression and anxiety
          Background Risk prediction tools may help identify youth who are at risk of developing depression or anxiety and allow personalised preventive interventions to be delivered. However, with concerns for implementation, it is important to directly engage with youth to understand their attitudes. Objective To qualitatively explore UK-based youth attitudes towards risk prediction tools and personalised preventive interventions for depression and anxiety. Methods Online semistructured interviews were conducted with a convenience sample of youth aged 16–25 years (n=25) and analysed using reflexive thematic analysis. Findings Analysis generated four themes: (1) Helpful or harmful: risk prediction as a ‘double-ended sword’ explores the potential benefits and consequences of risk scores; (2) ‘Taken with a grain of salt’: are risk prediction models the way forward? focuses on participants’ scepticism towards risk prediction tools, including ethics and privacy; (3) ‘It really depends on the person’: respecting the individual in prevention emphasises the importance of personal choice and individual differences and (4) ‘You still need like a person in the process’: the importance of human involvement encapsulates participants’ belief regarding human involvement in development and implementation. Conclusions While youth appear open to risk prediction tools and personalised preventive interventions, they highlighted concerns that must be addressed before implementation, including ethics, accuracy, privacy and feasibility. Clinical implications Going forward, researchers should prioritise stakeholder involvement, using active collaboration to identify ways in which these concerns can be addressed, which may increase acceptability and uptake. Human contact, alongside agency and choice, are further factors to consider.
          Higson-Sweeney, N., Peycheva, A., Breedvelt, J. J. F.
        • Cognition and future depression: associations with risk in those with and without a history of depression
          Background Cognitive impairments are common in depression and often persist beyond mood resolution. However, the relationship between cognitive performance, its neurological underpinnings, and future depression risk is unclear, limiting strategies for primary and secondary prevention. Objective Our objective was to determine whether cognition associates with subsequent depression, both relapse and first-episode occurrences. Methods 1862 UK Biobank participants with a history of International Classification of Diseases (ICD)-10-defined depression in remission (RD) (mean (SD) age: 52.7 (7.13) years) were age-matched and sex-matched to 1862 participants without depression history or current antidepressant use. Cognitive scores were compared between groups at the composite (z-score), domain and task levels. MRI-derived phenotypes assessed brain network structure and functional connectivity. Longitudinal associations with future depression were assessed using logistic regression models and a Cox proportional hazards model controlling for key confounders. Findings Participants with RD had a higher risk of future depression (33%) than controls (13%), including when we accounted for temporal differences in longitudinal assessment (HR=3.16 (95% CI 2.71 to 3.67), global proportional hazard assumption p=0.07). Composite cognitive performance in controls was inversely associated with future depression risk (risk estimated marginal means: 0.25% at –1SD, 0.20% at mean, 0.15% at +1 SD). In RD, this relationship was reversed (0.74% at –1SD, 0.90% at mean, 1.10% at +1 SD). Executive functioning, processing speed and reasoning task scores all contributed. Higher grey matter in default mode network regions was associated with better concurrent cognitive performance across all participants, but not with future depression risk. Other MRI findings were limited. Conclusions RD carried a threefold higher risk of future depression than controls. Cognitive performance was a risk marker for future depression in both groups but in opposing directions. Neuroimaging metrics provided little predictive value. Clinical implications Personalised risk factor assessment for depression is likely to be dependent on depression history. Those without previous history of diagnosed depression are at higher risk of future depression when cognitive performance is lower at baseline. RD is a high-risk group for future depression, and those with relatively higher cognitive performance may be more likely to report future depressive symptoms.
          de Cates, A. N., Lee, A., Winchester, L., Ebmeier, K. P., Lalousis, P., Upthegrove, R., Murphy, S. E., Harmer, C. J., Nichols, T., Topiwala, A.
        • How can we make interventions more 'acceptable in mental health?
          Are we properly assessing the acceptability of mental health interventions from a service user’s point of view? A treatment can be efficacious and effective but still not acceptable to a service user. For example, someone with psychosis may find a treatment that improves symptoms but causes significant weight gain and sedation unacceptable. Despite significant progress being made in developing safe and effective interventions for mental health problems, a notable proportion of people remain in need. The reasons for this are complex. Part of the problem could be an inadequate focus on how ‘acceptable’ interventions really are to service users given their views and specific circumstances. Treatment acceptability has been a rather poorly defined concept. This has led to researchers using several methods to assess their own ideas about what service user acceptability is. This can include methods such as using recruitment and withdrawal data. But such data may not be true markers of acceptability to a service user. Current approaches to assessing acceptability need improvement. Existing acceptability questionnaire measures are not widely used and are often developed for specialist settings. Crucially, very few have had any stated involvement of people with mental health conditions in their development. This approach risks not listening to service users’ voices fully. Developing better ways of understanding and assessing service users’ views of treatment acceptability in mental health could have many benefits—including empowering individual service users to identify interventions that they can and cannot accept. It is time to better understand what ‘acceptable’ really means in mental health.
          Kabir, T.
        • Predictive analytics to direct clinical attention to complex patients with elevated suicide risk: enhancement of the Veterans Health Administration REACH VET model
          Background Suicide is a major public health concern, particularly among Veterans. The U.S. Department of Veterans Affairs Veterans Health Administration (VHA) employs the Recovery Engagement and Coordination for Health–Veterans Enhanced Treatment (REACH VET) model to prioritise high-risk patients for targeted clinical attention. Objective REACH VET 1.0 (RV 1.0) was developed on 2008–2011 data. To reflect changes in clinical practice and populations, VHA updated it to REACH VET 2.0 (RV 2.0). This study describes its development and validation. Methods RV 2.0 used longitudinal data from 7,248,170 VHA patients (4,967 suicide deaths) in 2018–2019, with 650 time-varying demographic, clinical and area-level predictors derived from a 2-year lookback (2016–2019). An ensemble of Elastic-Net logistic regression models was trained on 2018 data and evaluated monthly at the population level in 2019, focusing on the top 0.1% intervention risk tier. Analyses assessed model discrimination, suicide detection, risk concentration, subgroup consistency (sex, age and race/ethnicity) and performance relative to RV 1.0 using the same percentile-based risk strata. Results RV 2.0 outperformed RV 1.0 across all risk strata, with better discrimination (C-statistic 0.76 vs 0.69) and consistent performance across demographic subgroups. Within the top 0.1% of predicted risk, RV 2.0 identified more deaths, higher suicide rates and greater mortality risk concentration both when averaged across the 12 monthly 2019 test sets (5.6 vs 3.6; 83.6 vs 53.7 per 100,000 person-years; 21.0 vs 14.1) and when annualised for 2019 (67 vs 43; 2.7% vs 1.7%; 1,003 vs 644 per 100,000 person-years; 26.7 vs 17.1). Conclusions RV 2.0 improves suicide risk stratification among Veterans, demonstrating better performance and consistent prediction across subgroups and highlighting the need for regular model updates and evaluation. Clinical implications RV 2.0 enables targeted interventions and, since its national VHA implementation in June 2025, continues to support system-wide suicide prevention.
          Peluso, A., Ramirez Osorio, J., Kazanis, W. H., Robinson, A., Martins, S. B., Cook, H., Callaway, K., Schaefferkoetter, N., McCarthy, J. F., Oliva, E. M., Kapadia, A., Trafton, J. A.
        • Unheard voices: the overlooked mental health toll of climate change in vulnerable communities
          Climate change has an increasing physical and mental health toll on young people globally. In this Perspective, we suggest that the extent of mental health impacts is likely to be underestimated in the low- and middle-income countries which are most vulnerable to the effects of climate change. We highlight a strong global inverse relationship between internet connectivity and climate vulnerability, which poses significant challenges for understanding climate change’s worldwide mental health impacts and for developing effective mitigation strategies. Inclusive methodologies that enable engagement with offline but climate-vulnerable communities are therefore needed. Such locally grounded mental health research is essential to ensure that climate policies are informed by the lived experiences of populations on the frontlines of the crisis, many of whom remain digitally disconnected and excluded from much current research.
          Zeljic, K., Rasolomalala, N., Michalek, J. E., Solomon, S., Rasamison, H., Ramaroson, S., Hadfield, K., Mareschal, I.
        • Challenges and solutions to participation in mental health clinical trials: Count Me In 2.0
          Mental health clinical trials in the UK face significant recruitment barriers, with mental health studies comprising just 3.3% of approved interventional medicinal product trials. Challenges include the limited numbers of trials and clinician gatekeeping—where clinicians decide whether or not to inform patients about research opportunities, limiting patient awareness and recruitment. The ‘Count Me In’ (CMI) approach, an opt-out recruitment model launched in Oxford in 2021 and then in Liverpool City Region in 2024, aimed to address these issues by directly contacting patients to discuss research opportunities, empower them in the shared decision process and embed participation in research into real-world clinical care. In this paper, we discuss the need for advancing beyond the original CMI model, including the requirement for enhanced data capture, mechanism for patient outreach that prioritises inclusive practices for improving participation and ensuring diverse, representative trial populations.
          Bifarin, O., Bryant, T., Harvey, M., Smith, K., Miah, J., Thai, J., Ramjaun, G., Edwards, S., Jones, H., Cipriani, A., Joyce, D. W.
        • Unmasking microaggressions: Experiences of women in clinical and academic psychiatry and the need for systemic reform
          Microaggressions constitute a pervasive and insidious form of discrimination, frequently manifesting as subtle, unconscious and unintentional actions that disproportionately affect individuals based on gender, race, ethnicity, religion, age, sexual orientation, culture or disability. Although such phenomena are observed across a wide range of contexts, the present perspective article focuses specifically on women working as providers of healthcare services in psychiatry. For these professionals, microaggressions commonly take the form of implicit biases, dismissive attitudes and unequal treatment, all of which contribute to a professional environment in which their contributions are systematically undervalued. These behaviours are reinforced by cultural norms and entrenched systemic practices, which serve to normalise discrimination, impede career progression and contribute to psychological distress. Addressing such stereotypes and discriminatory practices at both micro and macro levels is therefore essential. This article draws on both the existing literature and collective personal experiences, arguing that the complexity of microaggressions in psychiatry necessitates a multidimensional analytical approach. By incorporating the perspectives of 21 women psychiatrists and psychologists from 15 countries across six continents, this perspective identifies recurring challenges related to service delivery and career progression. Cross-regional analysis reveals persistent patterns, including commentary on physical appearance, dismissal of professional contributions, violations of personal boundaries and forms of structural marginalisation. These findings extend the academic understanding of microaggressions in psychiatry and underscore the need for systemic reform and cultural transformation.
          Ojeahere, M. I., Szczegielniak, A. R., Niu, H., Jatchavala, C., Vahdani, B., Heshmati, S., Karaliuniene, R., Kilic, O., Naskar, C., Nahidi, M., Hayatudeen, N., Nofal, M., Jaguga, F., Martinez Guardado, M. G., Adiukwu, F. N., Hidalgo, E., Abiri, G., Saeed, F., Orsolini, L., Pinto da Costa, M., Khan, N.
        • Automatically detecting trends and open questions from mental health publications: a Wellcome-funded GALENOS project
          Background More effective and better tolerated treatments are urgently needed for people with mental health disorders, such as anxiety, depression and psychosis. However, the rate of translation of positive results from early phase studies into clinically validated treatments remains painstakingly slow. The scientific literature on mental health preclinical and early interventions is burgeoning at pace, making it difficult for researchers, practitioners and policymakers to identify and track new developments. Objective As part of the Wellcome-funded Global Alliance of Living Evidence for aNxiety, depressiOn and pSychosis project, we aimed to develop and evaluate an automated approach to track the evolution of mental health research over time, detect emerging trends and suggest open questions. Methods Our approach used topic modelling, large language models and time-series forecasting in combination. We applied our approach to a corpus of 182 747 titles and abstracts extracted from the OpenAlex database for 2015–2025. Using topic modelling to identify topics and then tracking topic mentions over time, we built a time series predictive model and predicted ‘trendiness’ based on sustained increased mentions above baseline expected from model predictions. We evaluated our approach retrospectively using a blinded expert study of a randomly selected sample of trending and not trending topics. Finally, we developed a novel topic-augmented generation approach to suggest open questions in trendy topics and evaluated the approach by comparison to baseline-generated questions without topic augmentation. Findings Our approach detected 973 topics and predicted 165 (17%) of those as trending. Key topics that the model predicted as trending included ‘ketamine for treatment-resistant depression’, ‘student mental health in academia’ and ‘COVID-19 psychosis’. We found that domain experts largely agreed with the model’s predictions of trendiness. Topic-augmented generated questions were more specific than baseline generated questions. Conclusions Our approach enables identification of new developments and open questions. Future work will improve temporal pattern tracking and use full texts. Clinical implications Our approach can support all stakeholders to gain an overview of the published literature, assess temporal patterns, identify trends and rank open questions.
          Hastings, J., Wosny, M., Kennett, J., Homiar, A., Malhi, G. S., Furukawa, T. A., Potts, J., Thomas, J., Cipriani, A.
        • International Depression Questionnaire and International Anxiety Questionnaire: validation of brief ICD-11 measures for depression and generalised anxiety disorder
          Background The 11th revision of the International Classification of Diseases (ICD-11) introduced revised diagnostic criteria for a depressive episode (DE) and generalised anxiety disorder (GAD). The International Depression Questionnaire (IDQ) and the International Anxiety Questionnaire (IAQ) are the first self-report measures developed to assess and screen these disorders according to the ICD-11 diagnostic rules. Objective This study aims to validate the IDQ and the IAQ in clinical and community samples, examining internal consistency, factorial validity and construct validity. Methods The cross-sectional, observational multicentre validation study applied internal consistency testing, confirmatory factor analyses and item response theory (IRT) in a clinical sample (n=569; age 18–73; 417 females, 118 males, 34 diverse) and a sample representative of the German general population (n=1001) by age, education and gender (500 females, 499 males, 2 diverse). Factorial and IRT model fit of the IDQ and IAQ as well as concordance with the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder-7 (GAD-7) was tested. Results Both questionnaires showed excellent internal consistency (=0.96 each) and strong factor loadings. A three-factor IDQ model and a one-factor IAQ model provided the best fit. In the clinical sample, 39.7% met ICD-11 DE criteria and 51.0% GAD criteria (overlap 32.2%). In the general population, prevalence was 5.9% for DE and 9.3% for GAD. Concordance with PHQ-9 and GAD-7 was partial, suggesting differences between ICD-11-based and established screening tools. Conclusions The IDQ and IAQ are psychometrically robust self-report measures for ICD-11 DE and GAD. They are reliable, valid, brief, easy to administer, cost-free and suitable for use in primary care and research across diverse clinical and research settings. Their availability supports standardised screening of depression and GAD in both clinical and community settings.
          Schröder, J., Kratzer, L., Karatzias, T., Semm, A., Tschöke, S., Biedermann, S., Schäflein, E., König, J., Knefel, M., Hyland, P., Shevlin, M.
        • Functional near-infrared spectroscopy assessment of the effects of transcranial direct current stimulation combined with transcranial magnetic stimulation on dynamic functional networks in patients with chronic insomnia: randomised, double-blind, parallel-group, controlled clinical trial
          Background Evidence suggests that transcranial direct current stimulation (tDCS) combined with repetitive transcranial magnetic stimulation (rTMS) is more effective than either modality alone. However, the underlying neural mechanisms remain unclear. Objective To explore the effects of combined tDCS-rTMS on cortical functional networks and neural regulation processes in chronic insomnia. Methods In this randomised, double-blind, sham-controlled trial, 111 adults with chronic insomnia were allocated to real tDCS+real rTMS or sham tDCS+real rTMS. Participants received 20 weekday sessions over 4 weeks. Of these, 106 completed treatment and 103 provided functional near-infrared spectroscopy (fNIRS) data meeting predefined quality criteria. fNIRS measured oxygenated haemoglobin (Oxy-Hb) responses in prefrontal and temporal regions during a verbal fluency task (VFT) before and after treatment. The primary outcome was haemodynamic activation; secondary outcomes were functional connectivity and sleep quality. Findings Sleep quality improved in both groups, with significantly greater reduction in Pittsburgh Sleep Quality Index (PSQI) scores in the real tDCS+real rTMS group (p<0.05). No between-group differences were observed in VFT performance. However, the combined stimulation group showed significantly increased Oxy-Hb responses across multiple fronto-temporal channels, particularly in bilateral temporal regions, and greater enhancement in mean functional connectivity (p<0.05). Both interventions were well tolerated, with no serious adverse events. Conclusions This study provides neuroimaging evidence that combined tDCS and rTMS may improve chronic insomnia by enhancing activation of fronto-temporal cortices and strengthening inter-regional functional connectivity. These findings offer objective support for the clinical efficacy of the combined stimulation protocol, link neurophysiological changes to treatment optimisation and suggest potential advantages of this approach for neuromodulation-based therapeutic strategies. Clinical implications These findings suggest that tDCS combined with rTMS may represent a feasible and well tolerated non-pharmacological strategy for chronic insomnia, with potential advantages over rTMS alone at both clinical and neurophysiological levels. Trial registration number This study was registered as a clinical trial with the China Clinical Trial Registration Centre (ChiCTR2100052681).
          Zhou, Q., Liu, Z., Li, C., Wang, Q., Zheng, T., Zhou, D.-s., Yu, H., Yu, C.
        • Clinical guidelines on self-harm and suicide prevention: taking uncertainty into account in the evidence base
          The National Institute for Health and Care Excellence (NICE) guideline for self-harm advises against the use of risk assessment tools to predict future occurrence of repeat self-harm or suicide in individuals who have self-harmed, or to inform decisions regarding their treatment and discharge. In this perspective article, we discuss shortcomings in the process of developing this guideline, including: (1) limitations in the NICE evidence review underpinning these recommendations, which resulted in very minimal evidence being included; (2) developing definitive recommendations and drawing strong conclusions regarding the limited predictive ability and potential harms of tools, which were almost entirely based on the committee’s expertise and experience and (3) not acknowledging the uncertainty and gaps in the evidence base, particularly around model impact, acceptability and feasibility. We highlight new evidence since this 2022 guideline, including examples of international work assessing model implementation and cost-effectiveness. We propose that there is an urgent need for more rigorous primary research assessing model impact, feasibility and acceptability, as well as empirical work addressing concerns about potential harms and misuse of tools, notably the denial of care. While prediction models should not be prematurely implemented in clinical practice without adequate validation and impact assessment, well-developed and validated tools in this area have the potential to improve clinical care for individuals who self-harm. Future updates to the guideline should be informed by emerging higher quality evidence in the field.
          Seyedsalehi, A., Fazel, S.
        • Genetic investigation of non-affective psychosis and depression as causal risk factors for dementia
          Background Major psychiatric disorders are associated with increased risk of dementia but establishing whether psychiatric disorders causally increase dementia risk is challenging because dementia pathology can precede clinical diagnosis by decades. Prodromal psychiatric symptoms may arise long before cognitive decline, leaving open the possibility of reverse causation. Objective We aimed to determine whether non-affective psychosis or depression credibly causally influence dementia risk using a design robust to reverse causation. We tested whether people with psychiatric disorders who later develop dementia show reduced genetic liability to Alzheimer’s disease (AD) compared with dementia cases without such history. Methods We compared AD genetic liability, measured by polygenic risk scores (PRS) among dementia cases (N=7936) with and without prior non-affective psychosis (N=56) or depression (N=937) in the UK Biobank. We examined whether schizophrenia or major depressive disorder (MDD) PRS correlates with dementia liability to assess whether shared trait liability contributes to the association. Findings Dementia cases with prior non-affective psychosis or depression had lower AD genetic liability than those without a psychiatric history (psychosis: B=–0.29, 95% CI (–0.54 to –0.05), p=0.036; depression: B=–0.12, 95% CI (–0.18 to –0.05), p=0.0004), which is inconsistent with the hypothesis that the association between psychiatric disorders in dementia is explained by prodromal dementia effects. After excluding people with psychiatric diagnoses, neither schizophrenia nor MDD liability showed the negative correlations with AD liability in people with dementia expected if trait liability to those disorders per se contributed to dementia risk. Our findings instead are consistent with exposure to the disorders themselves as being associated with dementia. Conclusions Our findings are consistent with the hypothesis that psychiatric disorders are associated with increased vulnerability to dementia. Clinical implications Identification of potentially modifiable mechanisms for the association and optimal management of non-affective psychosis and depression may help reduce long-term dementia risk and inform prevention strategies.
          Escott-Price, V., Simmonds, E., Owen, M. J., ODonovan, M.
        • Mental health research for a world in climate crisis
          The accelerating climate crisis is reshaping not only the physical world but also the psychological landscapes in which individuals and communities attempt to live, learn and adapt.1 2 However, a paucity of psychiatric studies on mental disorders associated with climate change is evident, highlighting a need for climate–mental health research and policy that is contextually grounded, culturally inclusive and scientifically robust.3 4 The collection of articles featured in this special collection illuminates this rapidly evolving terrain from multiple vantage points—educational, cultural, clinical, methodological and epidemiological—revealing a shared urgency. Across school systems in the Global North, climate change education remains an underdeveloped domain despite young people expressing high levels of concern about the future. Mottishaw and MacQuarrie remind us that preparing youth for a destabilised climate requires more than scientific literacy: it demands recognising and constructively engaging with the complex emotional responses...
          dos Santos, M., Rao, M., Martens, P., Wainwright, L.
        • Using electronic health records to evaluate a children and young peoples social prescribing service: challenges and implications for research and practice
          Background Preliminary evidence indicates that social prescribing (SP) can improve children and young people’s (CYP) well-being but is limited by small non-representative samples and often relies on descriptive statistics. Given the wide implementation of SP in the UK, administrative records provide a unique opportunity to understand current practice and assess impacts on well-being. Objectives (1) To understand the quality of data captured in SP administrative records. (2) To explore which CYP are currently receiving SP and what SP entails in practice. (3) To assess the impact of SP on well-being. Methods We used administrative records from one CYP SP service in England. Records were extracted from Joy, an online platform for managing SP. Over 18 months, 770 age-eligible CYP were referred to SP, 203 of whom were successfully discharged and completed two pre-post measures of well-being (the short Warwick-Edinburgh Mental Wellbeing Scale; SWEMWBS) at least 7 days apart. We used descriptive statistics, a paired t-test to assess changes in well-being and linear regressions with interactions to test effect modification. Findings Missing data was the largest issue, with ethnicity missing for 94% of CYP. A lack of detail and inconsistent recording for both individual characteristics and SP practices also presented challenges. Despite this, we identified that most CYP were referred by their GP, followed by their school, with 97% referred because of their mental health. The most common pathway was to receive SP for around 90 days, with 10–15 link worker contacts and 6 contact hours. Following SP, SWEMWBS scores improved by 3.72 points (t(202)=17.50, 95% CI 3.30 to 4.14, p<0.001), a 20% relative increase. Exploratory analyses suggested that this increase was greater for those with lower baseline well-being. Conclusions Despite numerous challenges with missing data and data quality, we found that CYP well-being increases following SP (as it is currently implemented). The moderate effect size was consistent with larger studies of adults. Clinical implications Further development of online platforms is needed to monitor access to, nature of and efficacy of SP. For those working in SP, we recommend more training, implementation of standardised guidelines and designated time to update records.
          Bone, J. K., Bu, F., Fancourt, D., Hayes, D.
        • Trends in antipsychotic drug utilisation and indication in the paediatric population: a nationwide cohort study in Sweden
          Background Data on antipsychotic use for the Swedish paediatric population is limited. Objective We assessed the incidence, likely indication and extent of off-label antipsychotic use among children and adolescents in Sweden. Methods In this nationwide register-based study, individuals younger than 18 years with at least one antipsychotic dispensing between 1 January 2008 and 31 December 2021 were identified. Yearly age-standardised and sex-standardised incidence per 1000 persons was estimated and temporal trends were assessed using Poisson log-linear regression. We also assessed the likely indication and the proportion of on-label and off-label use. Findings Among 4 108 171 individuals who were children or adolescents at some point during the study period, 24 742 initiated antipsychotic treatment at least once, contributing 25 576 incident dispensings during the study period. Incidence increased from 0.48 to 1.28 per 1000 persons (risk ratio, RR per year 1.08, 95% CI 1.05 to 1.11; cumulative increase 180%), with a more pronounced rise in females (0.43 to 1.51 per 1000; RR 1.11, 95% CI 1.10 to 1.12; 284%) than males (0.53 to 1.06 per 1000; RR 1.06, 95% CI 1.05 to 1.07; 113%), driven by adolescents aged 12–17 years. The largest drug-specific increases were observed for quetiapine (0.04 to 0.33 per 1000; RR per year 1.18, 95% CI 1.17 to 1.19; cumulative increase 804%) and aripiprazole (0.03 to 0.36 per 1000; RR per year 1.16, 95% CI 1.14 to 1.18; cumulative increase 608%). A likely indication was identified in 64.3% (n=16 455) of incident dispensings, most commonly autism spectrum disorder (15.4%), attention-deficit hyperactivity disorder (10.9%) and anxiety disorders (9.6%). Among those with an identifiable indication, 81% were dispensed off label, mainly due to non-approved indications (64.8%) and most frequently among adolescent females. Conclusions In the paediatric population in Sweden, incidence of antipsychotic use increased between 2008 and 2021, especially among adolescent females and most incident dispensing with an identifiable indication were off label, underscoring the need to evaluate the long-term effectiveness and safety of antipsychotics in children and adolescents. Clinical implications These patterns highlight the need to evaluate the long-term effectiveness and safety of antipsychotics in children and adolescents.
          S Kamgang, K.-H., Pasternak, B., Reutfors, J., Pradhan, R., Wintzell, V.
        • Risk of unnatural death following self-harm in South Africa: development and validation of multivariable prognostic models
          Background Recurrent self-harm is common and is associated with an increased risk of unnatural death including suicide and fatal accidents. We developed and validated prognostic models to stratify individuals by risk of unnatural death after healthcare presentation for non-fatal self-harm to support clinical decision-making and targeted prevention when capacity to deliver evidence-based intervention is limited. Methods We used insurance claims and vital registration data from 6846 South African medical insurance beneficiaries aged ≥10 years who were discharged alive after healthcare presentation for self-harm during 2011–2021 to develop and validate models predicting unnatural death after non-fatal self-harm. We fitted competing-risk regression models to predict unnatural death within 1–3 years after presentation and discharge. Variable selection was guided by the least absolute shrinkage and selection operator. We used bootstrapping for internal validation and estimated optimism-corrected concordance indices (C-index), calibration intercepts and slopes, and for risk stratification the proportions of unnatural deaths captured across predicted-risk groups. Final models included age, sex, encounter characteristics, prior psychotropic medication use and selected prior mental disorder diagnoses. Results The final models achieved optimism-corrected C-indices of 0.74 at presentation and 0.75–0.76 at discharge and identified 86–88% of observed unnatural deaths within 2 years among the 40% of individuals with the highest predicted risk. Models showed little evidence of systematic miscalibration (optimism-corrected calibration intercepts –0.02 to –0.01), but some overfitting (optimism-corrected calibration slopes 0.84–0.92). Using the model with the highest optimism-corrected C-index, the simplified discharge model, the observed 2-year risk of unnatural death was 0.15% (95% CI 0.06% to 0.32%) among the 60% of individuals with the lowest predicted risk, comparable to the risk among 1 249 760 individuals without a self-harm history (0.14%, (95% CI 0.14% to 0.15%)). Conclusions The prediction models effectively rank individuals accessing private sector care in South Africa by their probability of unnatural death following healthcare presentation for non-fatal self-harm. Clinical implications The models are intended to support clinical decision-making and guide the prioritisation of individuals with predicted high risk for targeted interventions, supporting more efficient allocation of mental health care capacity, which is often limited in low- and middle-income settings.
          Whitesell Skrivankova, V., Pelteret, R., Rabie, S., Tlali, M., Folb, N., Rohner, E., Chinogurei, C., Ruffieux, Y., Seedat, S., Davies, M.-A., Maartens, G., Joska, J., Haas, A. D.
        • Mood instability and mental health service use in autism and attention-deficit/hyperactivity disorder: a natural language processing analysis of CRIS electronic healthcare records from 21 906 children and adolescents
          Background Children and young people (CYP) with neurodevelopmental diagnoses such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have high child and adolescent mental health service (CAMHS) needs. Mood instability is a common and impairing emotion dysregulation-related symptom linked to increased adult psychiatric service use; however, its role in CAMHS trajectories remains unclear. We aimed to examine whether baseline mood instability was significantly associated with time to discharge and annual CAMHS use in CYP with ASD and/or ADHD. Methods We applied natural language processing (NLP) to extract mentions of mood instability within 3 months of ASD or ADHD index diagnosis from electronic health records of 21 906 CYP referred to CAMHS between 2008 and 2022. We used accelerated failure time models and negative binomial regression to assess associations between baseline mood instability and time to discharge and annual CAMHS use, adjusting for clinical and sociodemographic confounders. Findings Mood instability was associated with increased annual CAMHS use across ASD (adjusted incidence rate ratio (aIRR) 1.24, 95% CI 1.08 to 1.42), ADHD (aIRR 1.47, 95% CI 1.30 to 1.67) and ASD+ADHD (aIRR 1.27, 95% CI 1.12 to 1.44) groups. While mood instability had no significant effect on discharge timelines in autistic children with or without ADHD, it was linked to reduced time to discharge in the ADHD group (aTR 0.76, 95% CI 0.69 to 0.84). Associations were most pronounced in those not receiving ADHD medication in the ADHD group (aIRR 1.67, 95% CI 1.47 to 1.89; aTR 0.70, 95% CI 0.61 to 0.79). Conclusions Mood instability was significantly associated with elevated CAMHS use in CYP with neurodevelopmental conditions, with differential effect across diagnostic groups. This may reflect both variations in clinical expression of mood instability and configuration of neurodevelopmental CAMHS provision. Clinicalimplications These findings suggest the importance of assessing emotion dysregulation in care planning and pathway allocation in neurodevelopmental CAMHS. NLP offers a time- and cost-efficient approach to surface and structure clinical data from electronic CAMHS records for scalable clinical research on complex constructs such as mood instability.
          Seker, A., Kim, S., Chandler, S., Colling, C., Patel, R., Sonuga-Barke, E., Downs, J.
        • De-implementing treatments from the healthcare system: trauma-focused versus non-trauma-focused therapy of post-traumatic stress disorder as an example
          Recently, a proposal was made to de-implement ineffective or harmful psychotherapeutic treatments from the healthcare system. Given the potential wide-ranging implications of this proposal, a critical review is warranted. As an example of an ‘implementation failure’, the authors of the proposal discussed non-trauma-focused treatments of post-traumatic stress disorder (PTSD). For this reason, we reviewed the evidence for non-trauma-focused psychotherapies compared with trauma-focused or exposure-based psychotherapies of PTSD in adults, published in the recent 7 years. We focused on efficacy and safety as the central criteria for potential (de-)implementation. The majority of meta-analytical results showed non-trauma-focused psychotherapies to be non-inferior to trauma-focused psychotherapies. In only a few analyses, non-inferiority was not found or exposure therapy achieved statistically significantly better effect sizes, which, however, were small and not clinically significant. Furthermore, non-trauma-focused psychotherapies were found to be safe and well-tolerated with low dropout. Hence, key criteria for de-implementation are not met. The results question the claim that non-trauma-focused therapies constitute an implementation failure. Thus, the example of trauma-focused versus non-trauma-focused psychotherapy of PTSD highlights fundamental problems associated with the proposal to de-implement specific treatments from the healthcare system. The reviewed results suggest that researcher allegiance may have an important impact on (de-)implementation decisions and needs to be rigidly controlled for. Several open questions remain, including consented criteria on which de-implementation decisions would be based, who decides about the actors responsible for making these decisions and, crucially, the mechanisms by which those in positions of authority are held accountable.
          Leichsenring, F., Milrod, B., Luyten, P.
        • Association of psychotropic medications with the use of coercive measures and recidivism during forensic psychiatric care: a Swedish nationwide register-based study
          Background Patients in forensic psychiatric care (FPC) are often treated with various psychotropic medications. However, evidence regarding their effectiveness in this setting is lacking. Objective The study aimed to estimate how different psychotropic medications are associated with the use of coercive measures and recidivism during FPC. Methods In this observational national register-based study, we included all patients newly registered as admitted to FPC in Sweden between January 2009 and August 2024. Exposures included major classes of psychotropic medication (typical antipsychotics, atypical antipsychotics, antidepressants, hypnotics and sedatives, antiepileptic medications, opioids, medications for addictive disorders and mood stabilisers), antipsychotic treatment strategies (no use, monotherapy, polypharmacy, long-acting injectables or clozapine) and specific antipsychotic agents. Outcomes were the use of coercive measures and recidivism into criminal behaviour. We performed a within-individual analysis using conditional generalised estimating equation models, where the risk of outcomes was compared between exposed and non-exposed time periods. Findings In total, 2690 patients were included, of which 25.1% experienced at least one occasion of coercion and 27.1% at least one event of recidivism during FPC. Atypical antipsychotics were associated with a reduced risk of subsequent use of coercive measures (OR 0.70, 95% CI 0.55 to 0.89) and recidivism (OR 0.79, 95% CI 0.63 to 0.99). Medication for addictive disorders was associated with a reduced risk of coercive measures by 34% (OR 0.66, 95% CI 0.47 to 0.93). Among antipsychotic agents, clozapine was associated with the largest risk reduction in the use of coercive measures (OR 0.48, 95% CI 0.33 to 0.69) and recidivism (OR 0.49, 95% CI 0.33 to 0.74). There was no significant difference between long-acting injectable, oral monotherapy or polypharmacy. Conclusions We observed that atypical antipsychotics, especially clozapine, were associated with a risk reduction for coercive measures and recidivism during FPC. Additionally, medications for addictive disorders were associated with a reduced risk of coercive measures. Clinical implications Our results can help inform decision-making processes in this clinical setting regarding pharmacotherapy but should be interpreted as one of many aspects influencing treatment success in FPC.
          Sitter, T. M., Savinen, S., Andine, P., Fernqvist, A., Edberg, H., Brikell, I., DOnofrio, B. M., Hirvikoski, T., Kuja-Halkola, R., Szwajda, A., Fazel, S., Nilsson, T., Chang, Z.
        • Depressive symptoms in chronic kidney disease: the hidden role of uremic toxins
          Background Depression is closely linked to neuroinflammation, and in chronic kidney disease, the accumulation of uremic toxins (UTs) may promote neuroinflammatory processes through the activation of inflammatory pathways. Objective The objective of this longitudinal study was to evaluate the association between UTs and depressive symptoms in a large, well-characterised cohort of non-dialysed adults with chronic kidney disease, a population in which this relationship had not yet been investigated. Methods The Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort comprised 3033 CKD stage 2–5 patients with 5 years of follow-up. Changes over time in depressive symptoms were assessed on the Center for Epidemiologic Studies Depression (CESD) scale. Mixed models were used to examine associations between the change in the CESD score and baseline levels of the UTs phenylacetylglutamine (PAG), indoxyl sulphate (IS), indole-3-acetic acid (IAA), p-cresyl sulphate, kynurenine, kynurenic acid and trimethylamine N-oxide. Findings 2165 patients were included (median age: 68 years; mean estimated glomerular filtration rate (eGFR): 35 mL/min/1.73 m²; median baseline CESD score: 7; mean follow-up time: 4.0 years). After adjustment for confounders, the CESD score was found to have increased by 0.11 (0.04 to 0.18) points per year. A doubling in PAG level was associated with an additional increase of 0.06 (0.01 to 0.18) points per year in the CESD. A doubling in IS and IAA levels was associated with a higher mean CESD score (0.20 (0.01 to 0.39) for IS and 0.28 (0.05 to 0.50) for IAA) but not with the score’s change over time. Conclusion PAG was significantly associated with changes in CESD score over time. Higher IS and IAA levels were linked to higher mean scores. Further studies are needed to confirm these results and to determine whether lowering serum UT levels would help to manage depressive symptoms in patients with CKD. Clinical implications Further research is needed to clarify the role of UTs; a better understanding could uncover novel metabolic pathways and inform new therapeutic strategies to complement the management of depressive symptoms.
          Levassort, H., Liabeuf, S., Boucquemont, J., Hafez, G., Laville, S. M., Lange, C., Frimat, L., Combe, C., Fouque, D., Laville, M., Jacquelinet, C., Herpe, Y.-E., Montalescot, L., Larabi, I. A., Alencar de Pinho, N., Massy, Z. A., Alvarez, J.-C., Pepin, M., on behalf of CKD-REIN, CKD-REIN, Pinho, Cannet, Combe, Fouque, Frimat, Hamroun, Herpe, Jacquelinet, Laville, Liabeuf, Massy, Morel, Pascal, Pecoits-Filho, Schanstra, Stengel, Lange, Lambert, Metzger
        • Risk of subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm episode among young people: a population-based cohort study
          Background Self-harm in young people is associated with elevated risks for subsequent self-harm, suicide attempts and suicide, particularly during the first year. Yet the trajectory across sex, age and self-harm methods remains poorly understood. Objective To estimate risk for subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm event in young people. Methods This study included 77 647 individuals (57.0% female) whose first hospital-treated (ie, within inpatient or outpatient specialised healthcare) self-harm episode occurred between ages 10–24 years during 1973–2019. We estimated cumulative incidence and incidence rate for subsequent self-harm, suicide attempts and suicide at 1 month, 3 months and 1 year following the initial episode. Findings Within 1 year, the cumulative incidence was 17.3% (95% CI 17.0 to17.5) for subsequent self-harm, 8.3% (8.1 to 8.5) for suicide attempt and 0.3% (0.2 to 0.3) for suicide. The highest risks occurred in the first month: 8.4% (8.2 to 8.6) for self-harm, 2.9% (2.8 to 3.0) for suicide attempt and 0.04% (0.03 to 0.05) for suicide. In the first month, the incidence rate of self-harm was 2.97 per 1000 person-days (2.90 to 3.05), falling to 0.55 (0.54 to 0.56) over the year. The suicide attempt rate declined from 0.98 (0.94 to 1.02) to 0.24 (0.24 to 0.25) and the suicide rate from 0.013 (0.009 to 0.019) to 0.007 (0.006 to 0.008). Males exhibited the highest suicide risk and females the highest attempts risk. First-month self-harm risk was greatest among males and children aged 10–12. Conclusions The month following a self-harm episode is marked by an elevated risk of subsequent self-harm, suicide attempts and suicide, yet risk remains elevated over the full year. Clinical implications These findings underscore the need for both acute and sustained prevention efforts. Special attention should be given to males and children aged 10–12 presenting with self-harm of ambiguous intent, as their risk of repetition may otherwise go unrecognised.
          Nguyen, T.-D., Karemyr, M., Kuja-Halkola, R., DOnofrio, B. M., Chang, Z., Brikell, I., Lichtenstein, P., Larsson, H., Sullivan, P., Lu, Y., Bjureberg, J.
        • Building evidence on digital psychotherapies for adults living with depression: a systematic scoping review of populations, interventions and design features of ongoing and planned randomised controlled trials
          Background Digital psychotherapies may offer scalable options for depression, but most randomised controlled trials (RCTs) are at moderate or high risk of bias. Mapping the methodologies, populations, interventions and outcomes of completed, ongoing and terminated/withdrawn RCTs of digital psychotherapies for depression could help anticipate future evidence gaps and redundancies. Study selection and analysis We conducted a systematic scoping review of RCTs registered in the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, European Union Clinical Trials Register and European Union Clinical Trials Information System between 2018 and 2025. Eligible RCTs evaluated digital psychotherapies for adults with depressive disorders, bipolar depression or depressive symptoms. Extracted data encompass methodological features, population characteristics, settings, description of intervention, control, funders, registration timing and reporting practices. Findings Among the 681 RCTs, 51.8% were completed, 34.1% published their results, 78.1% were prospectively registered and 8.5% were industry funded. Multicentre RCTs accounted for 23.1%, with 42.9% being planned in the USA, Germany or Canada and 25.1% recruiting in low- or middle-income countries. Inclusion relied on self-reported symptoms only for 61.5% and suicidal ideation was an exclusion criterion in 61.8%. The most frequent type of digital psychotherapy was cognitive-behavioural therapy for 64.6%. Human support was a component of the intervention in 44.2%. Chatbots were assessed by 4.6%. Waitlist control was used in 21%, with 49.3% of RCTs being open-label. The most frequent primary outcome was the Patient Health Questionnaire-9 for 35.7%. Conclusion Strengthening future evidence on digital psychotherapies requires timely dissemination of results, use of active controls, diversifying assessed psychotherapies and studying efficacy in populations with limited access to psychotherapy.
          Durante, E. K., Veal, C. J., Thibout, B., Macon-Dauxerre, V., Ravaud, P., Chevance, A.
        • Emulated trial of artificial intelligence use and subsequent depressive outcomes in a survey of US adults
          Background Generative artificial intelligence (AI) use has been suggested to have adverse mental health consequences but a causal relationship has not been examined. Objective To simulate a randomised controlled trial of AI use in a work, school or personal context by applying target trial emulation to multiple waves of data from a nationally representative survey. Methods We conducted a target trial emulation using non-probability survey data from three waves of a nationally representative survey conducted between 18 June 2024 and 8 January 2025. Participants aged ≥18 years reported generative AI use frequency at baseline. High-frequency use was defined as multiple times per week or more. The primary outcome was depressive symptom severity measured using the Patient Health Questionnaire 9-item (PHQ-9) at follow-up. Generalised causal forests assessed heterogeneity of treatment effects. Findings Among 19 099 participants assessed at baseline, 2862 (15.0%) reported AI use at least multiple times per week. A subset of 3109 (16.3%) returned for follow-up. In the primary weighted analysis, high-frequency use was not significantly associated with change in PHQ-9 score at follow-up (mean difference –0.18, 95% CI –0.94 to 0.59; p=0.65). Multiple sensitivity analyses using alternate outcome definitions also did not identify significant causal effects. Generalised causal forests yielded no significant evidence of heterogeneity of effect (p=0.81). Conclusions In an emulated randomised trial among US adults, generative AI use was not associated with subsequent depressive symptoms. This result does not support the premise that AI use causes greater depressive symptoms, although adverse outcomes among vulnerable individuals cannot be excluded. Clinical implications AI use is unlikely to cause increased depressive symptoms among most US adults. Continued monitoring should clarify potential risks among vulnerable populations.
          Perlis, R. H., Gunning, F. M., Uslu, A., Santillana, M., Baum, M. A., Druckman, J. N., Ognyanova, K., Lazer, D.
        • Leveraging simulation to provide a practical framework for estimating the novel scope of risk of large language models in healthcare
          Background Large language models (LLMs) are rapidly entering clinical and consumer use, yet their probabilistic outputs have delivered a variety of unsafe user responses. Difficulties in quantifying and mitigating risks posed by LLMs threaten to stall regulatory evaluation and clinical deployment of LLM-based software as a medical device (LLM-SaMD). Practical approaches are needed to extend existing medical-device regulations to LLM-SaMDs. Objective To demonstrate how simulation can extend existing medical-device risk management frameworks for addressing LLM-SaMD-specific risks. Methods We implement a simulation-based methodology for estimating LLM-SaMD risk. Fourteen open-source models were evaluated on three safety-classification tasks: suicidal-ideation, therapy-request and therapy-like interaction detection. Synthetic datasets were generated by Gemini 2.5 Pro and evaluated by psychiatrists. Model false-negative rates informed estimates of P1, the likelihood that a hazard progresses to a hazardous situation, and P2, the likelihood that that situation results in harm. Findings LLM success at generating synthetic datasets varied by task, with strong performance for neutral and non-therapeutic content but frequent errors in suicidal-ideation and therapy-like interactions. Performance generally improved with model size. Estimated P1 values ranged from 1.1x10–⁸ to 1.6x10–⁴ and P2 from 4.9x10–⁵ to 5.1x10–3, spanning four orders of magnitude. Conclusions By linking model failure modes to structured pathways to harm, simulation can extend existing medical-device risk frameworks to help address the probabilistic and context-dependent risks of LLM-SaMDs. Clinical implications Simulation-based risk estimation offers a practical way to characterise the risk landscape for specific LLM-SaMD, patient population and clinical context combinations.
          Kalinich, M., Luccarelli, J., Santa Maria, J., Moss, F., Torous, J.
        • Infections and severe mental illness: a population-based matched cohort study
          Background It is unclear whether acute infections associated with short-term systemic inflammation influence the risk of severe mental illness (SMI). Objective To investigate relationships between acute infections and incident SMI using electronic health records from the UK. Methods Using data from the Clinical Practice Research Datalink Aurum (1 January 2007 to 15 June 2024), we conducted six matched cohort studies. Adults (≥18 years) with gastroenteritis (GE), lower respiratory tract infection (LRTI), skin and soft tissue infection (SSTI), urinary tract infection (UTI), sepsis and meningitis/encephalitis (positive control exposure) recorded in primary care were matched with up to five individuals without infection on age, sex and practice in calendar date order and followed for incident SMI (schizophrenia, bipolar disorder, other psychoses). We estimated HRs for SMI comparing those with and without each infection using Cox regression, stratified by match set, adjusting for potential confounders (deprivation, Charlson Comorbidity Index, alcohol, smoking, body mass index and ethnicity). Findings Our six study cohorts ranged from 2 089 168 adults (391 773 with SSTI, 1 697 395 without) to 106 155 (17 860 with meningitis/encephalitis, 88 295 without). Median follow-up ranged from 4.1 years (IQR 1.9–6.9) in the sepsis cohort to 5.7 years (IQR 2.6–9.8) in the meningitis/encephalitis cohort. After adjustment, each infection was associated with increased SMI risk: SSTI, HR 1.16 (95% CI 1.08 to 1.24); LRTI, 1.28 (95% CI 1.20 to 1.38); UTI, 1.44 (95% CI 1.31 to 1.58); GE, 1.53 (95% CI 1.42 to 1.65); sepsis, 1.69 (95% CI 1.52 to 1.88); and meningitis/encephalitis, 3.36 (95% CI 2.61 to 4.32). Conclusion Our findings suggest SMI risk is higher among adults with a range of acute infections compared with those without, with higher risks for the more severe infections meningitis/encephalitis and sepsis. Clinical implications Providing timely infection treatment, targeted mental health support following severe infections, and where appropriate offering relevant vaccinations, may limit SMI risk.
          Cadogan, S. L., Gore-Langton, G. R., Mansfield, K. E., Tazare, J., Fazel, S., Douglas, I. J., Morton, C., Mukadam, N., Warren-Gash, C.
        • ADHD medication discontinuation and non-adherence: a Norwegian population-based register study
          Background Poor persistence and adherence to attention-deficit/hyperactivity disorder (ADHD) medication is a significant barrier to effective long-term care, particularly during adolescence, yet age-specific and sex-specific trajectories remain poorly characterised. Objective To characterise medication initiation, discontinuation and long-term adherence patterns for children and adolescents diagnosed with ADHD in a real-world setting. Methods A nationwide retrospective cohort study, including 8961 children and adolescents (aged <18 years) with a new ADHD diagnosis in child and adolescent mental health services between 1 January 2010 and 31 December 2012, with follow-up until 31 December 2021. Main outcomes were medication initiation rates; time to first medication discontinuation, analysed using Kaplan-Meier estimates and restricted mean survival time at 1 year and longitudinal adherence, measured by the proportion of days covered over 9 years. Findings Of the 8961 individuals in the cohort (mean age at diagnosis, 12 years; 69% male), 6661 (74.3%) initiated medication, with a median time from diagnosis to initiation of 106 days (IQR 17–231); 55% initiated within 90 days. Discontinuation increased significantly with age; adolescents aged 15–17 years remained on treatment for 31.9 fewer days (95% CI –40.8 to –23.1; p<0.001) in the first year compared with children aged 5–11 years. Females also discontinued significantly earlier than males (difference –13.2 days; 95% CI –19.8 to –6.5; p<0.001). Longitudinal analysis confirmed that older age at initiation and female sex were associated with a significantly steeper decline in medication coverage over time. Conclusions Discontinuation and low adherence to ADHD medication were common and increased substantially through adolescence, with females at higher risk of early cessation. Clinical implications Late adolescence warrants closer clinical monitoring and shared decision-making to support appropriate treatment continuation or well-informed discontinuation, particularly for older adolescents and females. Integrating structured transition planning and attention to sex-specific barriers may help reduce avoidable non-adherence during this high-risk period.
          Garcia-Argibay, M., Hofstad, T., Bjelland, I., Cortese, S., Mykletun, A.
        • Research priorities for oral health in people with severe mental ill-health
          Background People with mental disorders bear an excessive burden of oral diseases. This burden can exacerbate the personal, social and economic impacts of mental disorders. There is a need for transformational research to tackle this problem, which should start with co-setting research priorities with people with lived experience and key stakeholders. Objective This national Priority Setting Partnership (PSP) aimed to identify the top 10 research priorities for oral health among people with mental disorders. Methods Following the James Lind Alliance approach, this three-stage PSP engaged people with mental disorders, carers and staff of all levels and decision-makers from healthcare, social care and non-governmental organisations. In stage 1, questions for research were gathered via an online survey. Summary questions were then formed and checked against existing evidence. In stage 2, unanswered questions were compiled into an online shortlisting survey. In stage 3, a consensus workshop was held to determine the top 10 research priorities. Findings From 1214 questions received in stage 1, 60 unanswered questions were formed. Based on 2377 shortlisting survey responses, the 25 top-ranked questions were taken to the consensus workshop, where the top 10 research priorities were determined by 27 participants. The most important research question was ‘What are the best ways to integrate oral health within physical health checks and follow-up care for people with severe mental ill-health?’ Other questions focused on the capability of primary care, mental health and dental teams in supporting oral health, integrated system-level models of dental care and financial incentives for professionals. Discussion This PSP identified the top 10 research priorities for oral health among people with mental disorders, which would guide future research and funding aimed at reducing the stark inequalities in oral health between this group and the general population. Clinical implications Addressing the priorities identified in this consultation through transformational research would lead to impactful changes in healthcare and public health practice and policy. This in turn would address the burden of oral diseases among people with mental disorders and contribute towards improving their mental and physical health and recovery.
          Joury, E., Heidari, E., Tracy, D., Barngkgei, I., Shiers, D., Johnston, G., Bhui, K.
        • Effect of home visiting support on maternal psychosocial needs and postnatal depression: emulating a target trial
          Background Adolescent and young adult (AYA) mothers often experience unmet psychosocial needs, and those under 25 years of age are at increased risk of perinatal depression. Although home visiting programmes may be beneficial, no controlled trial has evaluated a programme co-designed with first-time AYA mothers and grounded in their lived experiences. Objective We evaluated the effect of the co-designed Early Partnership programme on perceived fulfilment of psychosocial needs and postnatal depressive symptoms among first-time AYA mothers. Methods We emulated a target trial using data from a pragmatic historically controlled study in four Tokyo municipalities. Participants were primiparous women aged 16–25 years. The intervention group included 151 participants and the control group included 158 participants. The intervention group received intensive tailored home visits by multi-professional family support workers from pregnancy to 12 months postnatally, and the historical control group received publicly funded health and social services. Findings Retention at 12 months was high in both groups (intervention group, 82.1%; control group, 82.9%). For the primary outcome analysis, the intervention group had greater improvement in perceived fulfilment of psychosocial needs at 6 months postnatally (difference in mean changes 4.16, 95% CI 1.35 to 6.97, Cohen’s d 0.40, 95% CI 0.13 to 0.67) and 12 months postnatally (difference in mean changes 3.93, 95% CI 0.63 to 7.23, Cohen’s d 0.39, 95% CI 0.06 to 0.72) than the control group. Postnatal depressive symptoms were lower in the intervention group at 6 months postnatally (mean difference –1.54, 95% CI –2.70 to –0.38, Cohen’s d –0.34, 95% CI –0.59 to –0.08) and 12 months postnatally (mean difference –1.55, 95% CI –2.74 to –0.36, Cohen’s d –0.34, 95% CI –0.61 to –0.07). Well-being also improved at each time point, but estimates were imprecise. Conclusions The Early Partnership programme, co-designed with young mothers and delivered by multi-professional teams, was acceptable and effective in improving perceived fulfilment of psychosocial needs and postnatal depressive symptoms. Clinical implications These findings suggest that a person-centred and relationship-based home visiting model, delivered through a non-stigmatising design, may represent a plausible model of maternal care.
          Baba, K., Narita, Z. C., Yamasaki, S., Shinozaki, T., Niimura, J., Nakajima, N., Yamaguchi, S., Knowles, G., Devylder, J., Ayaya, S., Kumagaya, S.-i., Stanyon, D., Oikawa, N., Hosozawa, M., Nakanishi, M., Ando, S., Kasai, K., Miyashita, M., Hiraiwa-Hasegawa, M., Furukawa, T. A., Patel, V., Sawyer, S. M., Nishida, A.
        • Correction: Introducing artificial intelligence in acute psychiatric inpatient care: qualitative study of its use to conduct nursing observations
          Barrera A, Gee C, Wood A, et al. Introducing artificial intelligence in acute psychiatric inpatient care: qualitative study of its use to conduct nursing observations. Evidence-Based Mental Health 2020;23:34-38. This article was corrected after publication. The competing interests declaration has been amended to note that authors Oliver Gibson and Daniel Bayley are employees at Oxehealth, Oxford, UK. An ethical approval statement has been added to the article to specify that this project was approved as a quality improvement project by the Adult Directorate Quality Group at Oxford Health NHS Foundation Trust.
      Sage Journals
        • Eye Glint as a Novel Perceptual Cue in Human Vision
          Psychological Science, Volume 37, Issue 6, Page 428-447, June 2026. A subtle yet ubiquitous feature of the human face iseye glint—specular reflections from the surface of the eye that vary with the position of light sources in the environment. This study tested whether eye glint influences face perception, particularly ...
          Gwenisha J. Liaw, Colin J. PalmerDepartment of Psychology, National University of Singapore
        • Retributive Sentiments Track Both Deterrent and Compensatory Concerns in a Small-Scale Society and a WEIRD Sample
          Psychological Science, Volume 37, Issue 6, Page 392-410, June 2026. Evolutionary theories suggest that retributive sentiments evolved to deter antisocial behavior, yet psychological evidence shows punitive sentiments imperfectly optimize deterrence. Recent theories resolve this paradox, suggesting that retributive ...
          Léo Fitouchi, Manvir Singh
        • Motive Alignment Promotes Adolescents’ Proenvironmental Behavior: A Field Experiment in Two Cultures
          Psychological Science, Volume 37, Issue 6, Page 379-391, June 2026. Realizing a sustainable future requires the active participation of today’s young generations. How can we foster adolescents’ proenvironmental engagement? In a preregistered, cross-national, longitudinal field experiment, we tested a novel approach to ...
          Jenna Spitzer, Stathis Grapsas, Astrid M. G. Poorthuis, Fan Li, Yue Song, Sander Thomaes
        • Multitarget Visual Search Flexibly Switches Between Concurrent and Sequential Search Modes
          Psychological Science, Volume 37, Issue 6, Page 411-427, June 2026. Investigations into people’s ability to use multiple working memory representations to concurrently search for targets have led to mixed findings. Although the discourse has predominantly centered around capacity limits in multitarget search, we here ...
          Alex J. Hoogerbrugge, Christoph Strauch, Noa Hoevers, Christian N. L. Olivers, Tanja C. W. Nijboer, Stefan Van der Stigchel
        • Not All Practice Is Created Equal: Longitudinal Evidence From Over 40,000 Chess Players
          Psychological Science, Ahead of Print. In recent years, several scholars have argued that the influence of deliberate practice on expertise has been overstated. Others have contended that these critiques conflate deliberate practice with less effective forms of training. We analyzed a large, ...
          Daniel A. Southwick, Kyle W. Harwell, Garrett Wright, Joseph A. Olsen, Benjamin M. Ogles
        • Fidelity Versus Validity Using Anendophasia as an Example: Commentary on Nedergaard and Lupyan (2024) and Lind (2025)
          Psychological Science, Ahead of Print. Nedergaard and Lupyan (2024) presented four studies aimed at validating anendophasia (i.e., experiencing no inner speech).1However, Lind (2025) held that no one, including Nedergaard and Lupyan, has demonstrated that anendophasia exists. In both articles,...
          Russell T. HurlburtDepartment of Psychology, University of Nevada, Las Vegas
        • Commentary: On the Equal-Opportunity Jerk “Defense”: Rudeness Complicates Sexism Attributions but Comes at a Cost
          Psychological Science, Ahead of Print. Sexism is a pervasive and persistent problem. In their 2022 article “The ‘Equal-Opportunity Jerk’ Defense: Rudeness Can Obfuscate Gender Bias” (Psychological Science, Vol. 33, pp. 397–411), Belmi et al. argued that sexism can be obfuscated and go ...
          Shiyao Bao, Anna Bajet, Rocío Martínez, Johannes Müller-Trede, Isabelle Engeler, Sebastian Hafenbrädl
    Turmoil In Iran
      Human Rights Monitor
        • LIVING ON THE EDGE OF SURVIVAL – LAST PART June 25, 2026 2:16 pm
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          Iran HRM
        • When the Despot Discovers New Methods of Suppression June 24, 2026 3:34 pm
          Human creativity is always commendable, up to the point where it is weaponized to engineer new methods of suppression within an authoritarian regime—and in this specific case, within Iran’s religious dictatorship. The containment and eradication of freedoms, especially the freedom of thought through advanced technological, educational, and biometric structures have enabled the regime to exploit […]
          Iran HRM
        • Living on the Edge of Survival – Part III June 24, 2026 2:55 pm
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          Iran HRM
        • Living on the Edge of Survival – Part II June 23, 2026 1:06 pm
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          Iran HRM
        • The 126th Week of the “No to Execution Tuesdays” Campaign in 57 Prisons Across Iran June 23, 2026 12:42 pm
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          Iran HRM
        • Secret Detention Centers and Systematic Torture of Protesters June 23, 2026 12:31 pm
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          Iran HRM
        • Living on the Edge of Survival – Part I June 22, 2026 12:05 pm
          Rising living costs, widening gaps between income and household expenses, expanding poverty, and growing pressure on vulnerable populations across Iran Between 2024 and 2026, the continued rise in living costs and the rapid increase in the prices of goods and services placed growing pressure on Iranian households. Official statistics, statements by government officials, assessments by […]
          Iran HRM
        • Iran: Minors Military Training – The “Combatant Youths” Scheme to Sustain the Ruling establishment June 22, 2026 11:35 am
          How does the Islamic Republic in Iran violate international conventions and the fundamental rights of children to preserve itself? Alarming reports of systematic violations of the rights of the child have re-emerged in a dangerous dimension. The issue of “weapon training for teenagers in Dishmok” (a town in Kohgiluyeh and Boyer-Ahmad Province) unveils a structural […]
          Iran HRM
        • Iran: Remembering the Past to Prevent Future Crimes; the Case of Alireza Shirmohammadali June 22, 2026 11:05 am
          The month of June in Iran serves as a reminder of one of the bitterest events in the history of Iranian prisons; the anniversary of the murder of Alireza Shirmohammadali, a 21-year-old political prisoner who, following his arrest due to online activities and sentence to imprisonment, lost his life after being stabbed in the Greater […]
          Iran HRM
        • Sacrificing Human Rights in Iran at the Altar of Energy Diplomacy June 17, 2026 4:55 pm
          While the world remains engrossed in the peace accord between Iran and the United States, counting down the moments for the reopening of the Strait of Hormuz to restore the global flow of oil and energy, the reality of sacrificing human rights remains glaringly obvious in this deal. There is no demand for the cessation […]
          Iran HRM
        Iran International