Research on mortality and admissions for physical health problems across eating disorder diagnoses in representative settings is scarce. Inequalities in these outcomes across a range of sociodemographic characteristics have rarely been investigated.

We investigated whether people with eating disorders had greater all-cause mortality and physical health-related in-patient admissions compared with those without eating disorders, and whether associations varied by sex, ethnicity, deprivation, age and calendar year at diagnosis.

Using primary care Clinical Research Practice Datalink linked to Hospital Episode Statistics, we matched people with an incident eating disorder diagnosis (any, anorexia nervosa, bulimia nervosa, eating disorders not otherwise specified, generic eating disorder or a referral code) from primary care Read codes to four people without eating disorders (1:4 matching) on year of birth, sex, primary care practice, year of registration and index date. We used univariable and multivariable Cox (mortality) and Poisson (admissions) models, and fitted interactions to investigate whether associations varied by sociodemographic characteristics.

We included 58 735 people (90.1% female, 91.6% White). People with any eating disorders had higher all-cause mortality (hazard ratio: 2.15, 95% CI: 1.73–2.67). Anorexia nervosa had the highest mortality (hazard ratio: 3.49, 95% CI: 2.43–5.01). People with any eating disorders had higher rates of planned (incidence rate ratio (IRR): 1.80, 95% CI: 1.4–1.87) and emergency admissions for physical health problems (IRR: 2.35. 95% CI: 2.35–2.46) and emergency admissions for injuries, accidents and substance misuse (IRR: 5.26, 95% CI: 5.24–5.29). Mortality and admission rate ratios were greater in males.

People with eating disorders have high rates of mortality and physical health-related admissions. Observed inequalities call for an understanding of why such inequalities exist. These findings highlight the need for prompt and effective treatment for eating disorders, and for improved guidance on primary care management of people with eating disorders.

Major depressive disorder (MDD) and insulin resistance-related conditions are major contributors to global disability. Their co-occurrence complicates clinical outcomes, increasing mortality and symptom severity.

In this study, we investigated the association of insulin resistance-related conditions and related polygenic scores (PGSs) with MDD clinical profile and treatment outcomes, using primary care records from UK Biobank.

We identified MDD cases and insulin resistance-related conditions, as well as measures of depression treatment outcomes (e.g. resistance) from the records. Clinical-demographic variables were derived from self-reports, and insulin resistance-related PGSs were calculated using PRS-CS. Univariable analyses were conducted to compare sociodemographic and clinical variables of MDD cases with (IR+) and without (IR−) lifetime insulin resistance-related conditions. Multiple regressions were performed to identify factors, including insulin resistance-related PGSs, potentially associated with treatment outcomes, adjusting for confounders.

Among 30 919 MDD cases, 51.95% were IR+. These had more antidepressant prescriptions and classes utilisation and longer treatment duration than patients without insulin resistance-related conditions (P < 0.001). IR+ participants showed distinctive depressive profiles, characterised by concentration issues, loneliness and inadequacy feelings, which varied according to the timing of MDD diagnosis relative to insulin resistance-related conditions. After adjusting for confounders, insulin resistance-related conditions (i.e. cardiovascular diseases, hypertension, non-alcoholic fatty liver disease, obesity/overweight, prediabetes and type 2 diabetes mellitus) were associated with antidepressant non-response/resistance and longer treatment duration, particularly when MDD preceded insulin resistance-related conditions. No significant PGS associations were found with antidepressant treatment outcomes.

Our findings support an integrated treatment approach, prioritising both psychiatric and metabolic health, and public health strategies aimed at early intervention and prevention of insulin resistance in MDD.

Accumulating evidence shows that an increasing number of children and young people (CYP) are reporting mental health problems.

To investigate emotional disorders (anxiety or depression) among CYP in England between 2004 and 2017, and to identify which disorders and demographic groups have experienced the greatest increase.

Repeated cross-sectional, face-to-face study using data from the Mental Health of Children and Young People surveys conducted in 2004 and 2017, allowing use of nationally representative probability samples of CYP aged 5–16 years in England. A total of 13 561 CYP were included across both survey waves (6898 in 2004 and 6663 in 2017). We assessed the prevalence of any emotional, anxiety and depressive disorder assessed using the Development and Well-Being Assessment and classified according to ICD-10 criteria.

The prevalence of emotional disorders increased from 3.9% in 2004 to 6.0% in 2017, a relative increase of 63% (relative ratio 1.63, 95% CI 1.38, 1.91). This was largely driven by anxiety disorders, which increased from 3.5 to 5.4% (relative ratio 1.63, 95% CI 1.37, 1.93). The largest relative changes were for panic disorder, separation anxiety, social phobia and post-traumatic stress disorder. Changes were similar for different genders and socioeconomic groups, but differed by ethnicity: the most pronounced increase was among White CYP (relative ratio 1.88, 95% CI 1.59, 2.24), compared with no clear change for Black and minority ethnic CYP (relative ratio 0.85, 95% CI 0.52, 1.39). Comorbid psychiatric conditions were present in over a third of CYP with emotional disorders, with the most common being conduct disorder.

Between 2004 and 2017, the increase in emotional disorders among CYP in England was largely driven by anxiety disorders. Socioeconomic inequalities did not narrow. Disaggregating by ethnicity, change was evident only in White CYP, suggesting differential trends in either risk exposure, resilience or reporting by ethnicity.

Despite evidence of associations between glucocorticoid treatment and adverse psychiatric and suicidal behaviour outcomes, large-scale observational evidence for serious outcomes is lacking.

To assess the risk of psychiatric and suicidal behaviour outcomes during glucocorticoid treatment.

Using Swedish population registers, we identified 1 105 964 individuals aged 15–54 years who collected a glucocorticoid prescription in oral form between 2006 and 2020. We investigated associations with a range of psychiatric outcomes: unplanned specialist healthcare contacts due to depressive, bipolar, anxiety or schizophrenia-spectrum disorders; and deaths by suicide or unplanned specialist healthcare contacts due to self-harm (‘suicidal behaviour’). We estimated hazard ratios from Cox proportional hazards models in a medication-only cohort by comparing outcome rates during and outside treated periods within individuals. We further identified individuals with an autoimmune or gastrointestinal autoimmune disorder diagnosis and compared hazards of the outcomes between those who did and did not initiate a glucocorticoid using a target trial emulation approach.

We found increased risks for psychiatric outcomes, with within-individual hazard ratios ranging from 1.08 (95% CI, 1.00–1.16) for depressive disorders to 1.23 (95% CI, 1.12–1.36) for bipolar disorder and 1.25 (95% CI, 1.20–1.31) for anxiety disorders. We found no clear association with suicidal behaviour (hazard ratio: 1.06; 95% CI, 0.96–1.17). These findings were similar when stratified by age and gender. Within-individual associations were attenuated in those diagnosed with an autoimmune disorder. The risk of anxiety and bipolar disorder outcomes appeared particularly elevated in the first weeks of treatment. Absolute rates were modestly elevated during treatment, and higher in those with a history of psychiatric disorders.

Glucocorticoid treatment is associated with elevated risks of serious psychiatric outcomes, including the onset and relapse of common psychiatric disorders. Individuals with psychiatric histories may require additional monitoring during glucocorticoid treatment.

Psychotic disorders are severe mental health conditions frequently associated with long-term disability, reduced quality of life and premature mortality. Early Intervention in Psychosis (EIP) services aim to provide timely, comprehensive packages of care for people with psychotic disorders. However, it is not clear which components of EIP services contribute most to the improved outcomes they achieve.

We aimed to identify associations between specific components of EIP care and clinically significant outcomes for individuals treated for early psychosis in England.

This national retrospective cohort study of 14 874 EIP individuals examined associations between 12 components of EIP care and outcomes over a 3-year follow-up period, by linking data from the National Clinical Audit of Psychosis (NCAP) to routine health outcome data held by NHS England. The primary outcome was time to relapse, defined as psychiatric inpatient admission or referral to a crisis resolution (home treatment) team. Secondary outcomes included duration of admissions, detention under the Mental Health Act, emergency department and general hospital attendances and mortality. We conducted multilevel regression analyses incorporating demographic and service-level covariates.

Smaller care coordinator case-loads and the use of clozapine for eligible people were associated with reduced relapse risk. Physical health interventions were associated with reductions in mortality risk. Other components, such as cognitive–behavioural therapy for psychosis (CBTp), showed associations with improvements in secondary outcomes.

Smaller case-loads should be prioritised and protected in EIP service design and delivery. Initiatives to improve the uptake of clozapine should be integrated into EIP care. Other components, such as CBTp and physical health interventions, may have specific benefits for those eligible. These findings highlight impactful components of care and should guide resource allocation to optimise EIP service delivery.

Some trials have evaluated peer support for people with mental ill health in high-income, mainly English-speaking countries, but the quality of the evidence is weak.

To investigate the effectiveness of UPSIDES peer support in high-, middle- and low-income countries.

This pragmatic multicentre parallel-group wait-list randomised controlled trial (registration: ISRCTN26008944) with three measurement points (baseline and 4 and 8 months) took place at six study sites: two in Germany, and one each in Uganda, Tanzania, Israel and India. Participants were adults with long-standing severe mental health conditions. Outcomes were improvements in social inclusion (primary) and empowerment, hope, recovery, health and social functioning (secondary). Participants allocated to the intervention group were offered UPSIDES peer support.

Of the 615 participants (305 intervention group), 337 (54.8%) identified as women. The average age was 38.3 (s.d. = 11.2) years, and the mean illness duration was 14.9 (s.d. = 38.4) years. Those allocated to the intervention group received 6.9 (s.d. = 4.2) peer support sessions on average. Intention-to-treat analysis showed effects on two of the three subscales of the Social Inclusion Scale, Empowerment Scale and HOPE Scale. Per-protocol analysis with participants who had received three or more intervention sessions also showed an effect on the Social Inclusion Scale total score (β = 0.18, P = 0.031, 95% CI: 0.02–0.34).

Peer support has beneficial impacts on social inclusion, empowerment and hope among people with severe mental health conditions across diverse settings. As social isolation is a key driver of mental ill health, and empowerment and hope are both crucial for recovery, peer support can be recommended as an effective component of mental healthcare. Peer support has the potential to move global mental health closer towards a recovery- and rights-based orientation.

Treatment guidelines recommend evidence-based psychological therapies for adults with intellectual disabilities with co-occurring anxiety or depression. No previous research has explored the effectiveness of these therapies in mainstream psychological therapy settings or outside specialist settings.

To evaluate the effectiveness of psychological therapies delivered in routine primary care settings for people with intellectual disability who are experiencing co-occurring depression or anxiety.

This study used linked electronic healthcare records of 2 048 542 adults who received a course of NHS Talking Therapies for anxiety and depression in England between 2012 and 2019 to build a retrospective, observational cohort of individuals with intellectual disability, matched 1:2 with individuals without intellectual disability. Logistic regressions were used to compare metrics of symptom improvement and deterioration used in the national programme, on the basis of depression and anxiety measures collected before and at the last attended therapy session.

The study included 6870 adults with intellectual disability and 2 041 672 adults without intellectual disability. In unadjusted analyses, symptoms improved on average for people with intellectual disability after a course of therapy, but these individuals experienced poorer outcomes compared with those without intellectual disability (reliable improvement 60.2% for people with intellectual disability v. 69.2% for people without intellectual disability, odds ratio 0.66, 95% CI 0.63–0.70; reliable deterioration 10.3% for people with intellectual disability v. 5.7% for those without intellectual disability, odds ratio 1.89, 95% CI 1.75–2.04). After propensity score matching, some differences were attenuated (reliable improvement, adjusted odds ratio 0.97, 95% CI 1.91–1.04), but some outcomes remained poorer for people with intellectual disability (reliable deterioration, adjusted odds ratio 1.28, 95% CI 1.16–1.42).

Evidence-based psychological therapies may be effective for adults with intellectual disability, but their outcomes may be similar to (for improvement and recovery) or poorer than (for deterioration) those for adults without intellectual disability. Future work should investigate the impact of adaptations of therapies for those with intellectual disability to make such interventions more effective and accessible for this population.

It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Premenstrual dysphoric disorder (PMDD) is common, with at least 3% of the female population affected by one or more of the typical mood symptoms of depression, irritability, mood swings and anxiety. The cyclicity and close relationship to the luteal phase of the menstrual cycle is characteristic for this syndrome and positive allosteric modulators (PAMs) on the GABAA receptor, especially allopregnanolone, are believed to be involved in the symptomatology.

To summarise the research on the role of PAMs and other neuroactive steroids in the pathophysiology of PMDD.

PubMed was searched for articles including the terms Premenstrual syndrome, AND neurosteroids OR allopregnanolone OR GABA OR oestradiol. Many additional publications were previously known to the authors and basic animal research was covered in a secondary step through reference lists.

There is evidence that allopregnanolone, like other PAMs of the GABAA receptor, is sedative in high concentrations and, in a minor proportion of the population, causes anxiety and irritability at lower levels, pointing to an inter-individual difference in sensitivity. In research comparing women with PMDD and healthy controls, differences in brain function and subcomposition of GABAA receptors related to levels of allopregnanolone have been found. Also, the varying levels of neuroactive steroids in general seem to worsen the symptoms. Supressed ovulation is effective but add-back hormones are necessary to prevent severe side-effects and could cause adverse mood in these individuals.

There is yet no effective treatment for PMDD available. Allopregnanolone seems to be a key provocateur of PMDD symptoms in susceptible individuals. Future research should focus on interventions that interfere with the effects of neurosteroids or the plasticity of the GABAA receptor itself.