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.

Profiling patients on a proposed ‘immunometabolic depression’ (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment.

To test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepressants.

Data on 2551 individuals with depression across the iSPOT-D (n = 967), CO-MED (n = 665), GENDEP (n = 773) and EMBARC (n = 146) clinical trials were used. Predictors included baseline severity of atypical energy-related symptoms (AES), body mass index (BMI) and C-reactive protein levels (CRP, three trials only) separately and aggregated into an IMD index. Mixed models on the primary outcome (change in depressive symptom severity) and logistic regressions on secondary outcomes (response and remission) were conducted for the individual trial data-sets and pooled using random-effects meta-analyses.

Although AES severity and BMI did not predict changes in depressive symptom severity, higher baseline CRP predicted smaller reductions in depressive symptoms (n = 376, βpooled = 0.06, P = 0.049, 95% CI 0.0001–0.12, I2 = 3.61%); this was also found for an IMD index combining these features (n = 372, βpooled = 0.12, s.e. = 0.12, P = 0.031, 95% CI 0.01–0.22, I2 = 23.91%), with a higher – but still small – effect size compared with CRP. Confining analyses to selective serotonin reuptake inhibitor users indicated larger effects of CRP (βpooled = 0.16) and the IMD index (βpooled = 0.20). Baseline IMD features, both separately and combined, did not predict response or remission.

Depressive symptoms of people with more IMD features improved less when treated with antidepressants. However, clinical relevance is limited owing to small effect sizes in inconsistent associations. Whether these patients would benefit more from treatments targeting immunometabolic pathways remains to be investigated.

High cognitive activity possibly reduces the risk of cognitive decline and dementia.

To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.

Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.

Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.

A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.

Hospital-treated self-harm is common and costly, and is associated with repeated self-harm and suicide.

To investigate the effectiveness of a brief contact intervention delivered via short message service (SMS) text messages in reducing hospital-treated self-harm re-presentations in three hospitals in Sydney (2017–2019), Australia. Trial registration number: ACTRN12617000607370.

A randomised controlled trial with parallel arms allocated 804 participants presenting with self-harm, stratified by previous self-harm, to a control condition of treatment as usual (TAU) (n = 431) or an intervention condition of nine automated SMS contacts (plus TAU) (n = 373), over 12 months following the index self-harm episode. The primary outcomes were (a) repeat self-harm event rate (number of self-harm events per person per year) at 6-, 12- and 24-month follow-up and (b) the time to first repeat at 24-month follow-up.

The event rate for self-harm repetition was lower for the SMS compared with TAU group at 6 months (IRR = 0.79, 95% CI 0.61–1.01), 12 months (IRR = 0.78, 95% CI 0.64–0.95) and 24 months (IRR = 0.78, 95% CI 0.66–0.91). There was no difference between the SMS and TAU groups in the time to first repeat self-harm event over 24 months (HR = 0.96, 95% CI 0.72–1.26). There were four suicides in the TAU group and none in the SMS group.

The 22% reduction in repetition of hospital-treated self-harm was clinically meaningful. SMS text messages are an inexpensive, scalable and universal intervention that can be used in hospital-treated self-harm populations but further work is needed to establish efficacy and cost-effectiveness across settings.

Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine.

To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before.

This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year.

Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24–0.54; P < 0.0001).

These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Late-life depression has been associated with volume changes of the hippocampus. However, little is known about its association with specific hippocampal subfields over time.

We investigated whether hippocampal subfield volumes were associated with prevalence, course and incidence of depressive symptoms.

We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1-weighted and fluid-attenuated inversion recovery 3T magnetic resonance images. Depressive symptoms were assessed at baseline and annually over 7 years of follow-up (9-item Patient Health Questionnaire). We used negative binominal, logistic, and Cox regression analyses, corrected for multiple comparisons, and adjusted for demographic, cardiovascular and lifestyle factors.

A total of n = 4174 participants were included (mean age 60.0 years, s.d. = 8.6, 51.8% female). Larger right hippocampal fissure volume was associated with prevalent depressive symptoms (odds ratio (OR) = 1.26, 95% CI 1.08–1.48). Larger bilateral hippocampal fissure (OR = 1.37–1.40, 95% CI 1.14–1.71), larger right molecular layer (OR = 1.51, 95% CI 1.14–2.00) and smaller right cornu ammonis (CA)3 volumes (OR = 0.61, 95% CI 0.48–0.79) were associated with prevalent depressive symptoms with a chronic course. No associations of hippocampal subfield volumes with incident depressive symptoms were found. Yet, lower left hippocampal amygdala transition area (HATA) volume was associated with incident depressive symptoms with chronic course (hazard ratio = 0.70, 95% CI 0.55–0.89).

Differences in hippocampal fissure, molecular layer and CA volumes might co-occur or follow the onset of depressive symptoms, in particular with a chronic course. Smaller HATA was associated with an increased risk of incident (chronic) depression. Our results could capture a biological foundation for the development of chronic depressive symptoms, and stresses the need to discriminate subtypes of depression to unravel its biological underpinnings.