Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence.

To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder.

This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions.

A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21–74%), 24% (95% CI: −15 to 63%) and 61% (95% CI: 35–86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder.

Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

A significant proportion of people with clozapine-treated schizophrenia develop ‘checking’ compulsions, a phenomenon yet to be understood.

To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive–compulsive symptoms (OCS).

Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample.

A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04–0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = −0.28, 95% CI −0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction.

We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians’ therapeutic decisions.

Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups.

To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire.

Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas.

A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased.

Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Introducing new disease-modifying therapies (DMTs) for Alzheimer's disease demands a fundamental shift in diagnosis and care for most health systems around the world. Understanding the views of health professionals, potential patients, care partners and taxpayers is crucial for service planning and expectation management about these new therapies.

To investigate the public's and professionals’ perspectives regarding (1) acceptability of new DMTs for Alzheimer's disease; (2) perceptions of risk/benefits; (3) the public's willingness to pay (WTP).

Informed by the ‘theoretical framework of acceptability’, we conducted two online surveys with 1000 members of the general public and 77 health professionals in Ireland. Descriptive and multivariate regression analyses examined factors associated with DMT acceptance and WTP.

Healthcare professionals had a higher acceptance (65%) than the general public (48%). Professionals were more concerned about potential brain bleeds (70%) and efficacy (68%), while the public focused on accessibility and costs. Younger participants (18–24 years) displayed a higher WTP. Education and insurance affected WTP decisions.

This study exposes complex attitudes toward emerging DMTs for Alzheimer's disease, challenging conventional wisdom in multiple dimensions. A surprising 25% of the public expressed aversion to these new treatments, despite society's deep-rooted fear of dementia in older age. Healthcare professionals displayed nuanced concerns, prioritising clinical effectiveness and potential brain complications. Intriguingly, younger, better-educated and privately insured individuals exhibited a greater WTP, foregrounding critical questions about healthcare equity. These multifaceted findings serve as a guidepost for healthcare strategists, policymakers and ethicists as we edge closer to integrating DMTs into Alzheimer's disease care.

Major depressive disorder (MDD) has been increasingly understood as a disruption of brain connectome. Investigating grey matter structural networks with a large sample size can provide valuable insights into the structural basis of network-level neuropathological underpinnings of MDD.

Using a multisite MRI data-set including nearly 2000 individuals, this study aimed to identify robust topology and connectivity abnormalities of grey matter structural network linked to MDD and relevant clinical phenotypes.

A total of 955 MDD patients and 1009 healthy controls were included from 23 sites. Individualised structural covariance networks (SCN) were established based on grey matter volume maps. Following data harmonisation, network topological metrics and focal connectivity were examined for group-level comparisons, individual-level classification performance and association with clinical ratings. Various validation strategies were applied to confirm the reliability of findings.

Compared with healthy controls, MDD individuals exhibited increased global efficiency, abnormal regional centralities (i.e. thalamus, precentral gyrus, middle cingulate cortex and default mode network) and altered circuit connectivity (i.e. ventral attention network and frontoparietal network). First-episode drug-naive and recurrent patients exhibited different patterns of deficits in network topology and connectivity. In addition, the individual-level classification of topological metrics outperforms that of structural connectivity. The thalamus-insula connectivity was positively associated with the severity of depressive symptoms.

Based on this high-powered data-set, we identified reliable patterns of impaired topology and connectivity of individualised SCN in MDD and relevant subtypes, which adds to the current understanding of neuropathology of MDD and might guide future development of diagnostic and therapeutic markers.

Higher intensity of psychotherapy might improve treatment outcome in depression, especially in those with comorbid personality disorder.

To compare the effects of 25 individual sessions (weekly) of two forms of psychotherapy – short-term psychoanalytic supportive psychotherapy (SPSP) and schema therapy – with the same treatments given for 50 sessions (twice weekly) in people with depression and personality disorder. Trial registration: NTR5941.

We conducted a pragmatic, double-randomised clinical trial and, over 37 months, recruited 246 adult out-patients with comorbid depression/dysthymia and personality disorder. A 2 × 2 factorial design randomised participants to 25 or 50 sessions of SPSP or schema therapy. The primary outcome was change in depression severity over 1 year on the Beck Depression Inventory II (BDI-II). Secondary outcomes were remission both of depression and personality disorder.

Compared with 25 sessions, participants who received 50 sessions showed a significantly greater decrease in depressive symptoms over time (time × session dosage, P < 0.001), with a mean difference of 5.6 BDI points after 1 year (d = −0.53, 95% CI −0.18 to 0.882, P = 0.003). Remission from depression was also greater in the 50-session group (74% v. 58%, P = 0.025), as was remission of personality disorder (74% v. 56%, P = 0.010).

Greater intensity of psychotherapy leads to better outcomes of both depression and personality status in people with comorbid depression and personality disorder.

Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis).

To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy.

We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models.

Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes.

Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity

International guidelines present overall symptom severity as the key dimension for clinical characterisation of major depressive disorder (MDD). However, differences may reside within severity levels related to how symptoms interact in an individual patient, called symptom dynamics.

To investigate these individual differences by estimating the proportion of patients that display differences in their symptom dynamics while sharing the same overall symptom severity.

Participants with MDD (n = 73; mean age 34.6 years, s.d. = 13.1; 56.2% female) rated their baseline symptom severity using the Inventory for Depressive Symptomatology Self-Report (IDS-SR). Momentary indicators for depressive symptoms were then collected through ecological momentary assessments five times per day for 28 days; 8395 observations were conducted (average per person: 115; s.d. = 16.8). Each participant's symptom dynamics were estimated using person-specific dynamic network models. Individual differences in these symptom relationship patterns in groups of participants sharing the same symptom severity levels were estimated using individual network invariance tests. Subsequently, the overall proportion of participants that displayed differential symptom dynamics while sharing the same symptom severity was calculated. A supplementary simulation study was conducted to investigate the accuracy of our methodology against false-positive results.

Differential symptom dynamics were identified across 63.0% (95% bootstrapped CI 41.0–82.1) of participants within the same severity group. The average false detection of individual differences was 2.2%.

The majority of participants within the same depressive symptom severity group displayed differential symptom dynamics. Examining symptom dynamics provides information about person-specific psychopathological expression beyond severity levels by revealing how symptoms aggravate each other over time. These results suggest that symptom dynamics may be a promising new dimension for clinical characterisation, warranting replication in independent samples. To inform personalised treatment planning, a next step concerns linking different symptom relationship patterns to treatment response and clinical course, including patterns related to spontaneous recovery and forms of disorder progression.

There are increasing calls for neurodivergent peoples’ involvement in research into neurodevelopmental conditions. So far, however, this has tended to be achieved only through membership of external patient and public involvement (PPI) panels. The Regulating Emotions – Strengthening Adolescent Resilience (RE-STAR) programme is building a new participatory model of translational research that places young people with diagnoses of attention-deficit hyperactivity disorder (ADHD) and autism at the heart of the research team so that they can contribute to shaping and delivering its research plan.

To outline the principles on which the RE-STAR participatory model is based and describe its practical implementation and benefits, especially concerning the central role of members of the Youth Researcher Panel (Y-RPers).

The model presented is a culmination of a 24-month process during which Y-RPers moved from advisors to co-researchers integrated within RE-STAR. It is shaped by the principles of co-intentionality. The account here was agreed following multiple iterative cycles of collaborative discussion between academic researchers, Y-RPers and other stakeholders.

Based on our collective reflections we offer general guidance on how to effectively integrate young people with diagnoses of ADHD and/or autism into the core of the translational research process. We also describe the specific theoretical, methodological and analytical benefits of Y-RPer involvement in RE-STAR.

Although in its infancy, RE-STAR has demonstrated the model's potential to enrich translational science in a way that can change our understanding of the relationship between autism, ADHD and mental health. When appropriately adapted we believe the model can be applied to other types of neurodivergence and/or mental health conditions.

The rising number of dementia diagnoses and imminent adoption of disease-modifying treatments necessitate innovative approaches to identify individuals at risk, monitor disease course and intervene non-pharmacologically earlier in the disease course. Digital assessments of dementia risk and cognitive function have the potential to outperform traditional in-person assessments in terms of their affordability, accuracy and longitudinal tracking abilities. However, their accessibility and reliability in older adults is unclear.

To evaluate the usability and reliability of a smartphone assessment of lifestyle and cognitive factors relevant to dementia risk in a group of UK-based older adults.

Cognitively healthy adults (n = 756) recruited through the Dementias Platform UK Great Minds volunteer register completed three assessments of cognitive function and dementia risk over a 3-month period and provided usability feedback on the Five Lives smartphone application (app). We evaluated cognitive test scores for age, gender and higher education effects, normality distributions, test–retest reliability and their relationship with participants’ lifestyle dementia risk factors.

Participants found the app ‘easy to use’, ‘quick to complete’ and ‘enjoyable’. The cognitive tests showed normal or near-to-normal distributions, variable test–retest reliabilities and age-related effects. Only tests of verbal ability showed gender and education effects. The cognitive tests did not correlate with lifestyle dementia risk scores.

The Five Lives assessment demonstrates high usability and reliability among older adults. These findings highlight the potential of digital assessments in dementia research and clinical practice, enabling improved accessibility and better monitoring of cognitive health on a larger scale than traditional in-person assessments.

Enduring ethnic inequalities exist in mental healthcare. The COVID-19 pandemic has widened these.

To explore stakeholder perspectives on how the COVID-19 pandemic has increased ethnic inequalities in mental healthcare.

A qualitative interview study of four areas in England with 34 patients, 15 carers and 39 mental health professionals from National Health Service (NHS) and community organisations (July 2021 to July 2022). Framework analysis was used to develop a logic model of inter-relationships between pre-pandemic barriers and COVID-19 impacts.

Impacts were largely similar across sites, with some small variations (e.g. positive service impacts of higher ethnic diversity in area 2). Pre-pandemic barriers at individual level included mistrust and thus avoidance of services and at a service level included the dominance of a monocultural model, leading to poor communication, disengagement and alienation. During the pandemic remote service delivery, closure of community organisations and media scapegoating exacerbated existing barriers by worsening alienation and communication barriers, fuelling prejudice and division, and increasing mistrust in services. Some minority ethnic patients reported positive developments, experiencing empowerment through self-determination and creative activities.

During the COVID-19 pandemic some patients showed resilience and developed adaptations that could be nurtured by services. However, there has been a reduction in the availability of group-specific NHS and third-sector services in the community, exacerbating pre-existing barriers. As these developments are likely to have long-term consequences for minority ethnic groups’ engagement with mental healthcare, they need to be addressed as a priority by the NHS and its partners.

Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown.

To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD.

National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored.

People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08–8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15–7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92–0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04–2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96–0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51–0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10–3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09–1.16, P < 0.001) were associated with worse therapy outcomes in PLWD.

Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.

It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions.

We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia.

Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression.

In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61–0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35–1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17–0.31).

High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention.

Despite its significance, ensuring continuity of care demands substantial resources, which might not be readily accessible in many public healthcare systems. Studies indicate that continuity of care remains uncertain in numerous healthcare systems.

This study aimed to assess the effectiveness of a continuity-of-care model for patients with severe mental illness (SMI), providing seamless treatment from discharge from a closed ward to subsequent psychiatric, psychological and rehabilitation services.

Data from patients discharged before (1 January to 31 December 2018) and after (1 June 2021 to 31 May 2022) full implementation of the model were analysed and compared in terms of average duration of hospital stay, emergency department visits within 90 days of discharge, readmission rate within a year post-discharge and initiation of rehabilitation process.

In the post-implementation period (n = 482), the average admission time significantly decreased from 30.51 ± 29.72 to 26.77 ± 27.89 days, compared with the pre-implementation period (n = 403) (P = 0.029). Emergency department visits within 90 days following discharge decreased from 38.70 to 26.35% of discharged patients (P < 0.001). The rate of readmission decreased from 50.9 to 44.0% (P = 0.041) for one readmission and from 28.3 to 22.0% (P = 0.032) for two readmissions in the year following discharge. Additionally, the proportion of patients entering formal rehabilitation increased from 7.94 to 12.03% (P = 0.044).

This study highlights the effectiveness of a continuity-of-care model spearheaded by senior psychiatrists and involving paramedical personnel. These findings underscore the significant potential of the model to substantially enhance mental health services and outcomes. Moreover, they emphasise its relevance for patients, clinicians and policy makers.

Anxiety in pregnancy and after giving birth (the perinatal period) is highly prevalent but under-recognised. Robust methods of assessing perinatal anxiety are essential for services to identify and treat women appropriately.

To determine which assessment measures are most psychometrically robust and effective at identifying women with perinatal anxiety (primary objective) and depression (secondary objective).

We conducted a prospective longitudinal cohort study of 2243 women who completed five measures of anxiety and depression (Generalized Anxiety Disorder scale (GAD) two- and seven-item versions; Whooley questions; Clinical Outcomes in Routine Evaluation (CORE-10); and Stirling Antenatal Anxiety Scale (SAAS)) during pregnancy (15 weeks, 22 weeks and 31 weeks) and after birth (6 weeks). To assess diagnostic accuracy a sample of 403 participants completed modules of the Mini-International Neuropsychiatric Interview (MINI).

The best diagnostic accuracy for anxiety was shown by the CORE-10 and SAAS. The best diagnostic accuracy for depression was shown by the CORE-10, SAAS and Whooley questions, although the SAAS had lower specificity. The same cut-off scores for each measure were optimal for identifying anxiety or depression (SAAS ≥9; CORE-10 ≥9; Whooley ≥1). All measures were psychometrically robust, with good internal consistency, convergent validity and unidimensional factor structure.

This study identified robust and effective methods of assessing perinatal anxiety and depression. We recommend using the CORE-10 or SAAS to assess perinatal anxiety and the CORE-10 or Whooley questions to assess depression. The GAD-2 and GAD-7 did not perform as well as other measures and optimal cut-offs were lower than currently recommended.

Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring.

To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK.

We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment.

We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally.

Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.