Parents influence and shape children's career choices through practical factors, including access to resources and emotional factors such as role modelling and support. Preliminary evidence suggests that this may be even more relevant in psychiatry. To explore perspectives about parental professional influence toward or away from a career choice in psychiatry at two levels: (a) past influence on practising psychiatrists of their parents and (b) current influence on their own children. Medical doctors working in child and adolescent psychiatry (n = 44) and their family members (n = 24) participated in a reflective online questionnaire. Data were analysed with qualitative thematic analysis. We found three main themes for influence of parental profession on career choice of doctors working in psychiatry: balancing autonomy and guidance (i.e. explicit, implicit and role modelling), influence of the sociocultural background of the family (i.e. family values, shared interest and bringing work home) and lived experience of mental disorders. We found similar themes for the influence of doctors working in psychiatry on career choice of their children, but subthemes differed (i.e. recognition of absence of neutrality and effects of parent's profession on the mental well-being of their children). Themes covered socialisation (participating in culture of the profession) and subjectification (development of person behind the professional), and not as much on qualification (competencies professionals need to qualify). Clinicians can apply the results as a framework to strengthen their professional identity, their own role modelling within their families and during teaching. Clinician educators and students may apply them to well-informed decision-making about career choice.
Real-world evidence on pharmacotherapy for bipolar disorder remains limited; in particular, the effectiveness of combination therapies that are widely used in clinical practice has not been systematically assessed. To assess the effectiveness of mono- and combination therapy with mood stabilisers and antipsychotics in preventing psychiatric hospitalisation. This population-based cohort study used a within-individual design and data from the National Database of Health Insurance Claims and Specific Health Check-ups of Japan. Patients aged ≥20 years, with a primary diagnosis of bipolar disorder treated in psychiatric settings between 1 April 2013 and 31 March 2022, were included. Follow-up continued until 31 May 2023. Exposures included monotherapy with mood stabilisers or antipsychotics, and combination therapy involving (a) lithium plus another mood stabiliser or (b) lithium, valproate or lamotrigine plus a commonly prescribed antipsychotic. The primary outcome was time to psychiatric hospitalisation. Adjusted hazard ratios (aHRs) with 95% confidence intervals were estimated using stratified Cox regression. Among 315 046 patients (median follow-up 7.1 years), 83 621 (26.5%) experienced psychiatric hospitalisation. Monotherapy with lithium (aHR 0.67 [0.66-0.68]), valproate (aHR 0.71, 95% CI 0.70-0.73), lamotrigine (aHR 0.72, 95% CI 0.69-0.75) and carbamazepine (aHR 0.74, 95% CI 0.70-0.78) was associated with reduced hospitalisation compared with non-use of any mood stabilisers. Antipsychotic monotherapy with 15 agents, including aripiprazole (aHR 0.73, 95% CI 0.70-0.75) and zotepine (aHR 0.74, 95% CI 0.69-0.79), was also associated with reduced risk compared with non-use of any antipsychotics. Combination therapy with lithium plus carbamazepine (aHR 0.73, 95% CI 0.64-0.83), zotepine (aHR 0.82, 95% CI 0.72-0.93), aripiprazole (aHR 0.87, 95% CI0.82-0.92) or valproate (aHR 0.92, 95% CI 0.87-0.97) was associated with further reductions in hospitalisation risk compared with lithium monotherapy. This large, population-based study showed that monotherapy and combination therapy with mood stabilisers and antipsychotics varied in their effectiveness in preventing psychiatric hospitalisation. These findings may inform treatment decisions in the clinical management of bipolar disorder.
People with psychosis have a life expectancy that is reduced by 15 years, mainly owing to preventable physical illnesses of which obesity is a precursor. Obesity is three times more common in individuals with psychosis, and antipsychotics are an important cause. Prediction could individualise obesity treatment, but current models are not fully actionable for individuals. To test whether antipsychotic-induced weight increase at 1 year is causally mediated by weight change in the first 12 weeks of treatment, and then develop and internally validate a causal actionable prediction pathway to prevent antipsychotic-induced obesity. This was a post hoc analysis of a clinical trial of olanzapine versus haloperidol which recruited 263 participants with first-episode psychosis. We conducted two distinct analyses: causal mediation and prediction modelling, within which there were two sequential models (a baseline model to predict 12-week outcome and a 12-week model to predict 1-year outcome), followed by counterfactual prediction. In the first analysis, we used parallel causal mediation analysis to determine the natural direct and indirect and total effects of antipsychotic choice on weight in 97 participants, considering two mediators: weight change from 0 to 12 weeks, and weight change from 12 to 52 weeks. In the second analysis, we first developed a baseline causal actionable prediction model to predict weight gain at 12 weeks in 172 participants and then a 12-week model to predict obesity at 1 year in 97 of the participants. Finally, we demonstrated counterfactual prediction. Antipsychotic-induced weight gain at 1 year appeared to be causally mediated by weight change during the first 12 weeks of treatment (indirect effect 5.70; 95% CI 2.83 to 8.66). At internal validation, the discrimination c-statistic for the baseline causal actionable prediction model was 0.728 (95% CI 0.661 to 0.801), and the calibration slope was 0.768 (95% CI 0.436 to 1.21). For the 12-week model, the c-statistic was 0.904 (95% CI 0.820 to 0.961), and the calibration slope was 0.601 (95% CI -0.0633 to 1.21). We used the models to predict the counterfactual outcomes of antipsychotic choice and 12-week weight change. Our results show that it may be early rather than later weight change that causally mediates antipsychotic-induced weight gain at 1 year. They also demonstrate the potential for causal actionable prediction of counterfactuals for true precision medicine, although this is tempered by the feasibility scope of this study and small sample size. Our results are hypothesis-generating and not yet clinically deployable.
Although lithium has been used effectively as a medication to treat bipolar and major depressive disorders, there are limited data defining lithium use patterns during pregnancy. To investigate trends and patterns of lithium prescribing in the perinatal period (before, during and after pregnancy) among pregnancies in the UK. We conducted a population-based study using primary healthcare records from the Clinical Practice Research Datalink GOLD, analysing 752 112 pregnancies during the period 1995-2018. We assessed the prevalence and patterns of lithium prescriptions, including discontinuation, continuation and dosage. Maternal characteristics were defined for lithium non-users and users, and between those who continued and discontinued use. From 1995 to 2018, the prevalence of lithium prescribing per 10 000 pregnancies was 3.02 (95% CI: 2.64, 3.44) before pregnancy, 1.89 (95% CI: 1.59, 2.23) during pregnancy and 2.81 (95% CI: 2.44, 3.21) postpartum. Prescribing during pregnancy was low across the study period, with the most recent prevalence in 2018 of 1.03 (95% CI: 0.26, 4.11) per 10 000 pregnancies. Among 337 pregnancies with perinatal lithium prescribing, 48.4% involved a diagnosis of bipolar disorder. Of 227 pregnancies where lithium was prescribed preconception, 15.4% continued treatment throughout pregnancy; discontinuation occurred before pregnancy in 20.7%, and during second or third trimester in 30.8%; 33.0% followed other prescribing patterns. Women who discontinued lithium were more likely to be younger, have a body mass index ≥30 kg/m2, a diagnosis of bipolar disorder, a history of smoking and >10 primary care consultations in the 12 months preconception, compared with those who continued treatment. Lithium prescribing during pregnancy in the UK is uncommon and discontinuation is frequent, particularly in the later stages of pregnancy. These findings highlight the need for proactive perinatal mental healthcare strategies and close clinical monitoring, to reduce unintentional first-trimester exposure while ensuring continuity of care for maternal mental health.
Children and adolescents with attention-deficit hyperactivity disorder (ADHD) have a higher likelihood of contact with child welfare services (CWS). Evidence on whether pharmacological treatment of ADHD reduces such contact is limited. To estimate the causal effect of pharmacological treatment of ADHD on CWS contact. In this quasi-experimental study, we used nationwide registry data covering all individuals aged 5-14 years and diagnosed with ADHD during 2009-2011 in Norway. We used linear probability models and instrument variable analyses to estimate the associations and causal effects of pharmacological treatment on CWS contact up to 4 years after diagnosis. As instrument variable analysis uses natural variation in treatment decisions between clinics as pseudo-randomisation, estimates inform effects for children and adolescents at the margin of treatment, i.e. patients whose treatment is more influenced by variation in treatment practice, e.g. due to less severe or atypical symptom presentation. A total of 5930 children and adolescents aged 5-14 years were diagnosed with ADHD between 2009 and 2011 (mean (s.d.) age 10.1 (2.4) years; 4380 males (73.9%)). Instrument variable analyses showed a reducing effect of pharmacological treatment on the use of supportive interventions by 11.9 percentage points (95% CI: -20.12, -3.80) and out-of-home-placement by 3.30 percentage points (95% CI: -6.44, -0.15) at 2-year follow-up. This corresponds to the numbers needed to treat estimates of 8 and 30, respectively. Pharmacological treatment of ADHD reduces CWS contact among children and adolescents at the margin of treatment, lowering the probability of receiving supportive interventions and out-of-home placements. Findings suggest that medication reduces behavioural symptoms, which may improve the family coping mechanism and reduces the need for CWS involvement. ISRCTN11891971.
Restrictive interventions are used in the treatment of some people with severe mental disorders such as psychosis - including psychiatric intensive care unit (PICU) admission, seclusion and restraint. Early Intervention in Psychosis (EIP) service input may improve outcomes in psychosis, but it is unclear whether specific components of EIP care reduce the need for restrictive practice. To examine associations between EIP care components, demographic characteristics and restrictive interventions. We conducted a retrospective cohort study of 14 874 people who used EIP services in England, using linked data from the National Clinical Audit of Psychosis and the Mental Health Services Data Set. We examined associations between EIP components and time to PICU admission (primary outcome) alongside seclusion/physical restraint/injected chemical restraint/requests for police assistance (secondary outcomes), using multilevel Cox regression, adjusting for demographic factors and clustering by service. Higher hazards of restrictive interventions were observed among men, younger people and several minority ethnic groups. Individuals eligible for clozapine who were not offered it (hazard ratio 1.51, 95% CI 1.20-1.91) or refused it (hazard ratio 1.46, 95% CI 1.02-2.10) had higher hazards of PICU admission than those not eligible, whereas those who were eligible for clozapine and received it did not. There was weaker evidence of similar effects on hazards of physical restraint and seclusion. Receipt of CBT for psychosis was associated with reduced hazards of PICU admission (hazard ratio 0.80, 95% CI 0.67-0.95) and physical restraint (hazard ratio 0.68, 95% CI 0.47-0.98). Substance use was associated with increased hazards of PICU admission and requests for police assistance, although substance use interventions appeared to partially mitigate this. Marked demographic disparities exist in the use of restrictive practice. Specific EIP care components may be associated with reductions. Strengthening evidence-based EIP provision and addressing structural inequalities may support progress towards less coercive and more equitable care.
Antidepressants are pivotal in treating major depressive disorder and other psychiatric conditions. However, despite their widespread use, evidence regarding the serious adverse effects of prolonged antidepressant use and withdrawal in complex older-adult populations remains limited. We aimed to investigate the association between phases of antidepressant treatment with emergency hospital admission and hospital admissions related to adverse drug reactions in older adults with polypharmacy in English primary care. We conducted a case-control study using linked primary and secondary care electronic health record data from the Clinical Practice Research Databank GOLD and Aurum. We included individuals aged 65-100 years with polypharmacy (i.e. those who were prescribed five or more medicines). We used conditional logistic regression to investigate the associations between the phases of antidepressant treatment and hospital admission risks. We found 626 199 emergency hospital admission cases and matched with 3 639 740 controls. The initiation phase of antidepressants was associated with the greatest increase in the risk of emergency hospital admission (adjusted odds ratio 2.30, 95% CI 2.23-2.38), followed by short treatment gap or early discontinuation after short-term use (adjusted odds ratio 1.41, 95% CI 1.37-1.45). We found that patients had a higher risk of serotonin-related symptoms, falls and trauma, and cardiovascular events during antidepressant use phases, and the risks tend to decrease in past exposure phases for most conditions. Individuals who are on the initiation and short treatment gap or early discontinuation after short-term use of antidepressant treatment are associated with a higher risk of hospital admission. This study highlights the need for vigilant monitoring of antidepressant initiation and withdrawal in older-adult polypharmacy patients.
Information about a treatment's benefits and harms available to a patient often relies on text. However, for many medical conditions, patients must trade off benefits and harms across multiple competing treatments. It remains unknown how to appropriately communicate information on benefits and harms to patients. We compared three communication tools using textual information (Cochrane summary of findings table) or increasing combinations of textual and graphical information (Kilim and Vitruvian plots, respectively) to convey the available evidence. Communication of Benefit-Risk Information, an online randomised controlled trial, is a three-group, parallel, open-label, automated, randomised controlled trial (no. NCT05917639). We recruited participants aged between 18 and 65 years from the general population. Participants were randomly allocated (1:1:1) to one of the three communication tools providing information on competing fictional treatments for social anxiety, and were asked to choose one based on externally provided preferences. The primary outcome was the perceived level of decisional conflict when selecting a treatment (decisional conflict scale (DCS): 0 = best, 100 = worst). Because this was an all-or-nothing, single-visit trial, only those participants providing data contributed to the primary analyses (modified intention to treat). We recruited 2178 adults between 1 June and 27 November 2023. Vitruvian and Kilim plots outperformed the Cochrane summary of findings table on the primary outcome (adjusted mean difference -10.9, 95% CI -13.5 to -8.2, P < 0.0001 and -9.7, 95% CI -12.4 to -7.1, P < 0.0001), respectively). Results varied by participants' literacy and numeracy skills, lived experience of the condition of interest, ethnic group, gender assigned at birth and age. Combining graphical and textual information, as opposed to text only, improved communication and reduced decisional conflict when choosing across multiple competing medical interventions. Organisations involved in disseminating scientific evidence should consider endorsing a combined graphical and textual approach and adopting more intuitive and accessible communication methods. We identified several prognostic factors that should inform the development of future patient decision aids and communication of scientific findings. NCT05917639.
Postpartum depressive symptoms can vary substantially and probably reflect distinct subtypes. Understanding specific symptom patterns may help identify those at risk for later psychiatric care. We aimed to identify subtypes of postpartum depressive symptoms and examine their associations with subsequent psychiatric care. We conducted a cohort study using Danish nationwide health registers linked to population-based Edinburgh Postnatal Depression Scale (EPDS) scores from 2015 to 2021. Latent class analysis of EPDS responses identified subtypes among women with clinically relevant symptoms (EPDS ≥11), using a maternal background population as a reference group (EPDS <11). The outcome was psychiatric hospital contacts or redeemed psychotropic prescriptions within 1 year postpartum. We estimated standardised cumulative incidence rates and risk ratios using spline-based, time-to-event models. Among 162 079 women, 11 847 (7.3%) had clinically relevant symptoms (EPDS ≥11). Five subtypes were identified: Mild-depressive (23%), Moderate-anxious (17%), Moderate-depressive (18%), Moderate-overwhelmed (31%) and Severe-depressive (11%). At 1 year, the standardised cumulative incidence of psychiatric care was 69.6 (95% CI, 61.4-79.0) per 1000 persons in the Mild-depressive subtype. Compared with this group, the adjusted risk ratio was 0.33 (95% CI, 0.28-0.38) in the background maternal population, between 1.11 (95% CI, 0.93-1.32) and 1.25 (95% CI, 1.06-1.48) across moderate subtypes and 2.37 (95% CI, 1.99-2.82) for the Severe-depressive subtype. Distinct subtypes of postpartum depressive symptoms were associated with varying risks of subsequent psychiatric care, depending on both symptom severity and symptom type. These findings underscore the importance of systematic screening and tailored follow-up, even for women with mild to moderate symptoms.
Many children and young people (CYP) with significant mental health difficulties face barriers to accessing care from mental health services, impacting their clinical outcomes and recovery. Sociodemographic and socioeconomic factors may contribute to inequalities in access and outcomes. To investigate the roles of sociodemographic, socioeconomic and clinical factors in influencing access to services, receipt of clinical care or diagnoses and clinical outcomes. Using data from a large, nationally representative, randomised controlled trial in England (STADIA), 1225 children aged 5-17 years and with emotional difficulties referred to child and adolescent mental health services (CAMHS) were followed up over 18 months post-referral to investigate predictors of referral acceptance, receipt of care and their clinical outcomes. Older CYP (for each 1-year increase in age, odds ratio 1.07, 95% CI: 1.02, 1.11) and those living in the least deprived neighbourhoods (deprivation index, least versus most deprived quintile: odds ratio 1.60, 95% CI: 1.05, 2.43) were more likely to have their referral accepted by CAMHS. Clinical severity (i.e. scoring above cut-off for symptoms and/or impact) was not associated with receipt of a clinical diagnosis or treatment/intervention. At 12-month post-referral, 61% met mental health 'caseness' criteria (v. 67% at baseline). CYP living in less deprived neighbourhoods had better clinical outcomes at 12-month follow-up (least versus most deprived quintile: odds ratio 0.49, 95% CI: 0.30, 0.81, for meeting caseness criteria, i.e. the presence of clinically significant symptoms and impairment). Females were more likely than males to have clinically significant levels of depression at 12-month follow-up (odds ratio 1.77, 95% CI: 1.28, 2.45). There appear to be sociodemographic and socioeconomic inequalities in access to care and outcomes for clinically referred CYP with emotional mental health difficulties, with limited improvements in clinical outcomes 1 year following referral to CAMHS. CYP living in more deprived areas and younger children appear less likely to receive help, hampering earlier intervention efforts even in help-seeking populations.
The American Society of Clinical Psychopharmacology convened a 45-member international expert task force to identify circumstances supporting the deprescribing of core psychotropic medications for major depressive disorder (MDD) and bipolar disorders. Three Delphi survey rounds plus a selective literature review identified points of consensus (predefined as ≥75% agreement) about when antidepressant, antipsychotic, mood stabiliser and sedative-hypnotic deprescribing is warranted. Twenty out of 32 statements (63%) achieved consensus across seven thematic areas. In MDD, panellists favoured discontinuing antidepressants when mechanisms of action are duplicative, adequate trials produce ≤25% improvement or loss of prior efficacy cannot be regained through dose increases or augmentations. Indefinite antidepressant maintenance in MDD was favoured after three or more lifetime episodes. In bipolar disorder, antidepressant deprescribing was favoured in the setting of rapid cycling, mixed features or emerging mania/hypomania symptoms; and discouraged if prior antidepressant cessation led to relapse. In nonpsychotic mood disorders, panellists favoured deprescribing antipsychotics that caused significant weight gain or tardive dyskinesia over adding pharmacological antidotes. Deprescribing to achieve an eventual medication-free status was considered inappropriate, in bipolar type 1, but not necessarily bipolar type 2 disorder. Although individualised circumstances necessarily inform psychopharmacology management, clinical presentations that misalign with existing pharmacotherapies may signal the desirability of cautious deprescribing.
Electroconvulsive therapy (ECT) is an established intervention for severe or treatment-resistant psychiatric illnesses, including depression, schizophrenia, mania and catatonia. Despite its efficacy, concerns over its risks have contributed to ongoing stigma and hesitancy regarding its use. Traditional clinical trials have demonstrated the superiority of ECT in symptom reduction compared with other treatments, yet are impractical for assessing rare or long-term outcomes. Observational studies using administrative health data can assess rare or long-term outcomes, but are limited by confounding/bias. This review synthesises evidence from studies utilising administrative health data and modern statistical methods to address clinically relevant questions about ECT's association with (a) dementia, (b) major adverse cardiovascular/cerebrovascular events, (c) suicide deaths and (d) all-cause mortality. Most studies indicate that, after adjusting for confounding, ECT does not increase the risk of dementia or major adverse cardiovascular/cerebrovascular events. Furthermore, ECT is likely associated with a substantial reduction in suicide mortality and all-cause mortality. Although observational studies cannot fully eliminate unmeasured confounding, the consistency of the findings from diverse investigators and congruence with clinical trials and neuroimaging studies lends support to their validity. These modern observational studies have yielded results that reinforce ECT's safety and efficacy supporting its position as a life-saving treatment.
Psychedelics are increasingly described as a new therapeutic approach in a variety of mental disorders including depression. Oral psychedelics such as psilocybin have an acute effect evolving over 6-8 h and are generally given in combination with psychological support. There is debate on the exact role of this support and how and by whom it should be delivered. This has significant implications for real-world implementation in health services post-licensing. In this feature, we discuss these issues and outline a model for psychological support delivery in publicly funded health services such as the National Health Service. We also suggest further research to explore the exact role of support in psilocybin treatment and identify the essential elements to direct service plans for clinical implementation. These steps are important: over recent decades, there have been few new treatments for depression, moreover, psychedelic drugs are appealing to patients, and accumulating data suggest that their efficacy may be long-lasting. However, realistic plans for implementation must be based on high-quality evidence and the needs of the whole patient population. This will ensure that these treatments, if licensed, are available not only for those able to pay but to all on an equitable basis.
People with affective psychotic disorders often face diagnostic delays and presentations are under-recognised at first contact with early intervention services (EIS). Despite their clinical significance, most research and service models for first-episode psychosis (FEP) have focused on non-affective psychoses. We sought to clarify the relative prevalence of affective psychoses in EIS. A systematic review and random-effects meta-analysis of observational studies reporting proportion of affective psychotic disorders among individuals presenting to EIS with FEP was conducted. Eligible studies included treated FEP populations diagnosed using DSM/ICD criteria. Searches were conducted in Web of Science, Medline and PsycINFO (inception to July 2025). The primary outcome was pooled proportion of affective psychotic disorders. Heterogeneity was assessed using Q-statistics and I2-statistics. Meta-regressions examined potential moderators, including urbanicity, national income level and geographical region. Eighty-three studies (N = 30 946; mean age 24.95 years; 34.78% female) were included. Random-effects pooled proportion was 18.0% (95% CI 15.4-20.6; 95% prediction interval 3.6-39.4%; I2 = 95.6%). Schizoaffective disorder represented 7.4% (k = 49; 95% CI 5.8-9.2). Schizophrenia was the most frequent diagnosis, with a pooled proportion of 45.5% (k = 79; 95% CI 40.3-50.7). Meta-regression analyses identified that affective psychoses were less common in Asia and more common in North America compared with Europe. Higher urbanicity was also associated with increased prevalence. Associations with national income level (NIL) were limited by small subgroup sizes. Affective psychotic disorders constitute a meaningful subgroup within EIS. This suggests better screening, targeted treatments and adaptive service models of care.
Few studies have quantitatively characterised the shared and distinct features of the epigenetic age signature of schizophrenia, bipolar disorder and major depressive disorder. To construct a multi-platform epigenetic clock tailored to human blood and brain tissues, and to characterise variations in epigenetic age acceleration across these three common psychiatric disorders. We integrated 31 publicly available DNA methylation data-sets generated on the platforms Illumina 27K, 450K and EPIC (850K) from patients with schizophrenia, bipolar disorder or major depressive disorder, and from matched controls. Using elastic net regression combined with sure independence screening, we developed the blood–brain clock and applied it to assess disorder-specific epigenetic age acceleration in blood and brain. The blood–brain clock achieved high accuracy across tissues and outperformed established predictors, particularly in brain samples. Epigenetic age acceleration was reduced in schizophrenia, increased in bipolar disorder and major depressive disorder and strongly elevated in Alzheimer’s disease (positive control). Alterations appeared earlier in blood than in brain. Meta-analysis confirmed that both reduced acceleration (schizophrenia) and increased acceleration (bipolar disorder, major depressive disorder, Alzheimer’s disease) were significantly associated with disease prevalence. Differential methylation analyses further revealed that the blood–brain clock probes captured disease-associated signals, with schizophrenia showing the greatest overlap with causal risk loci, and opposite methylation patterns distinguishing schizophrenia from bipolar disorder or major depressive disorder. A subset of blood DNA methylation probes enabled high-precision classification between schizophrenia and bipolar disorder or major depressive disorder. This blood–brain clock reveals distinct patterns of epigenetic age acceleration across psychiatric disorders, reflecting disorder-specific and shared biological ageing signatures. The manifestation of these alterations in peripheral blood highlights its potential as a non-invasive biomarker for early detection, risk stratification and differential classification of schizophrenia, bipolar disorder and major depressive disorder.
Schizophrenia has been proposed to be a disorder of accelerated ageing, characterised by a mismatch between biological and chronological age. Evidence accumulated over the past 15 years has examined this model using molecular, neuroimaging, cognitive and epidemiological markers. To evaluate whether schizophrenia shows evidence of an accelerated or advanced ageing phenotype across biological systems and to assess the consistency of the underlying molecular mechanisms. A systematic review (PROSPERO CRD42024574059) was conducted following PRISMA guidelines. PubMed and Google Scholar were searched for studies published after 2009 that cited the original accelerated ageing hypothesis publication or investigated ageing in the context of schizophrenia and/or psychosis. Evidence was synthesised narratively by domain, with emphases on meta-analyses and minimally treated, longitudinal cohorts. A total of 923 manuscripts were identified, and a final 170 were included in the systematic review. Schizophrenia showed a reproducible ageing phenotype, as evidenced by in increased mortality, higher dementia risk, brain-predicted age elevation and cognitive decline. BrainAGE studies revealed mean age gaps of 3-4 years, often present at first episode. At the mechanistic level, meta-analyses reported consistent telomere shortening (standardised mean difference approximately -0.4 to -0.5) and modest acceleration of selected epigenetic clocks. Dysregulation of oxidative stress, inflammation, mitochondrial function and insulin-like growth factor-1 signalling were frequent and partly preceded antipsychotic exposure. Schizophrenia is associated with a multisystem ageing phenotype underpinned by convergent biological mechanisms, most consistently involving telomere attrition and oxidative and/or inflammatory stress. The overall pattern supports a model of advanced rather than uniformly accelerated ageing, reflecting early biological deviation with parallel rather than steeper decline.
Depression is the most common mental illness globally and is a leading cause of years lived with disability. The manifestation of depressive symptoms can vary among ethnic groups. Individuals in South Asian countries experience higher levels of somatic symptoms than those in other regions, but it is not known whether this pattern extends to the South Asian diaspora. To provide a qualitative synthesis of what is known regarding depression symptoms among the South Asian diaspora in English-speaking countries. A systematic scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines, based on a pre-registered protocol (doi.org/10.17605/OSF.IO/5E6ZK). The review included qualitative, quantitative and mixed-methods primary research, reporting depression symptoms based on samples of adults of the South Asian diaspora in English-speaking countries with substantial South Asian populations. Qualitative content analysis was used to identify widely reported symptoms of depression among the South Asian diaspora. Commonly reported symptoms included physical pain, heart-related symptoms and repetitive negative thinking, none of which are included in ICD-11 diagnostic criteria for depressive disorders. Sleep-related disturbances are also widely reported in research into experiences of depression among the South Asian diaspora. Current diagnostic criteria for depression might not capture symptoms of some South Asian individuals, which may cause missed opportunities for intervention.
Identifying patients with first-episode psychosis (FEP) who are unlikely to achieve early clinical recovery (ECR) is critical for personalised intervention and resource allocation. ECR - defined as the concurrent achievement of symptomatic and functional remission - represents a clinically meaningful outcome that captures both illness control and functional reintegration. To develop and externally validate prediction models for ECR using clinical, cognitive and genetic data. We analysed two large, independent Spanish cohorts: the primeros episodios psicóticos cohort (N = 335), for model development and internal validation, and the Programa Asistencial a las Fases Iniciales de Psicosis cohort (N = 668), for external validation. Forty-seven baseline clinical and cognitive variables and 87 polygenic risk scores (PRSs) were examined. Predictors were selected using penalised logistic regression. Logistic regression and three machine learning algorithms were compared for discrimination, calibration and clinical utility. The best-performing model was a logistic regression using six routinely collected clinical and cognitive predictors (duration of untreated psychosis, days of treated psychosis, baseline functioning, insight, executive function and cognitive reserve), with an optimism-corrected area under the receiver operating characteristic curve of 0.73 in development and 0.63 in external validation. PRS models showed limited external generalisability and did not improve prediction. Machine learning algorithms offered no advantage over regression models. A simple, interpretable logistic regression model based on routine clinical and cognitive variables can predict early recovery in FEP with acceptable generalisability. These findings support the use of transparent, clinically grounded models in early psychosis care and highlight the current limitations of genetic predictors for individualised treatment.
Females are less likely than males to be diagnosed with attention-deficit hyperactivity disorder (ADHD). When diagnosed, females are older than males. In this study, we examined the childhood antecedents of later ADHD diagnosis and its impact on adolescent/emerging adult outcomes, with a focus on females. In this cohort study, we used data from a Welsh nation-wide electronic cohort of 13 593 individuals (n = 2680 (19.7%) females) diagnosed with ADHD and 578 793 individuals (n = 286 734 (49.5%) females) without ADHD. We compared females with later diagnoses (ages 12-25) to those with earlier, timely diagnoses (ages 5-11) and no diagnosis, in terms of childhood (ages 5-11) antecedents and adolescent/adult (ages 12-25) outcomes. We also tested for sex differences. Although females with earlier ADHD diagnosis showed more health and educational difficulties in childhood than those with later diagnosed ADHD (odds ratios ranged from 0.18 to 0.92), there was clear evidence of these difficulties in females with later diagnosed ADHD, compared with females without ADHD (odds ratios: 1.07-9.02). In adolescence/early adulthood, females with later diagnosed ADHD used more healthcare services and had worse mental health, educational and socioeconomic outcomes than females diagnosed earlier (odds ratios: 1.39-4.96) and those without ADHD (odds ratios: 1.54-23.98). Many of these outcomes were exacerbated in females compared with males. The results demonstrate that later ADHD diagnosis is associated with significant negative outcomes by adolescence and disproportionately disadvantages females. Despite later diagnosis, there was clear evidence of childhood mental health and educational difficulties when compared with females without ADHD. Therefore, timely childhood ADHD diagnosis may help to mitigate later risks, especially for females.
Mentalising skills may be conceptualised as composed by both personal and interpersonal competencies, in turn shaped by early adverse experiences and coping strategies. Although cross-sectional observations described a role for mentalising skills in burnout development, large-scale longitudinal studies on the topic remain limited, especially in relation to psychiatry training. The primary aim was to investigate protective and risk factors for higher burnout scores across time. Secondary aims included testing whether psychiatry exhibited different burnout scores across time in comparison to other medical residents. A cohort of 1803 medical residents (1131 psychiatry residents) was assessed for mentalising skills, conceptualised as composed of emotional regulation (Difficulties in Emotion Regulation Scale), interpersonal competencies (Interpersonal Competence Questionnaire), coping strategies (Coping Orientation to Problems Experienced) and burnout dimensions (Maslach Burnout Inventory). One-year follow-up was available for 520 psychiatry residents (73.03% response rate) and 234 other medical residents (35.94% response rate). Longitudinal mixed models and bivariate latent change models were employed. Across all residents, greater levels of burnout were associated with higher scores in insecure attachment, emotional dysregulation and maladaptive coping, as well as lower scores in interpersonal skills. Attending at least one supervision per month was associated with lower burnout scores across time. According to a bivariate latent change model, emotional regulation improvements through years were associated with lower burnout scores across time. In psychiatry residents, lower burnout scores across time were observed as compared to other medical residents. Psychiatry residents benefited from a higher protective effect of interpersonal competencies (group by moderator by time interaction) and coping strategies against burnout. Mentalising skills may mitigate burnout development. Training in psychiatry emerged as a potential mitigating factor against burnout increases. Structured supervisions may foster professional development and emotional resilience.