Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.

To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).

In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.

Younger age at onset (odds ratio 0.94, P = 7.79 × 10−13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10−4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10−3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.

People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.

Crisis resolution teams (CRTs) offer brief, intensive home treatment for people experiencing mental health crisis. CRT implementation is highly variable; positive trial outcomes have not been reproduced in scaled-up CRT care.

To evaluate a 1-year programme to improve CRTs’ model fidelity in a non-masked, cluster-randomised trial (part of the Crisis team Optimisation and RElapse prevention (CORE) research programme, trial registration number: ISRCTN47185233).

Fifteen CRTs in England received an intervention, informed by the US Implementing Evidence-Based Practice project, involving support from a CRT facilitator, online implementation resources and regular team fidelity reviews. Ten control CRTs received no additional support. The primary outcome was patient satisfaction, measured by the Client Satisfaction Questionnaire (CSQ-8), completed by 15 patients per team at CRT discharge (n = 375). Secondary outcomes: CRT model fidelity, continuity of care, staff well-being, in-patient admissions and bed use and CRT readmissions were also evaluated.

All CRTs were retained in the trial. Median follow-up CSQ-8 score was 28 in each group: the adjusted average in the intervention group was higher than in the control group by 0.97 (95% CI −1.02 to 2.97) but this was not significant (P = 0.34). There were fewer in-patient admissions, lower in-patient bed use and better staff psychological health in intervention teams. Model fidelity rose in most intervention teams and was significantly higher than in control teams at follow-up. There were no significant effects for other outcomes.

The CRT service improvement programme did not achieve its primary aim of improving patient satisfaction. It showed some promise in improving CRT model fidelity and reducing acute in-patient admissions.

Little is known about the long-term outcome of anorexia nervosa.

To study the 30-year outcome of adolescent-onset anorexia nervosa.

All 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971–1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed.

At the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism.

This long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.

Home treatment has been proposed as an alternative to acute in-patient care for mentally ill patients. However, there is only moderate evidence in support of home treatment.

To test whether and to what degree home treatment services would enable a reduction (substitution) of hospital use.

A total of 707 consecutively admitted adult patients with a broad spectrum of mental disorders (ICD-10: F2–F6, F8–F9, Z) experiencing crises that necessitated immediate admission to hospital, were randomly allocated to either a service model including a home treatment alternative to hospital care (experimental group) or a conventional service model that lacked a home treatment alternative to in-patient care (control group) (trial registration at ClinicalTrials.gov: NCT02322437).

The mean number of hospital days per patient within 24 months after the index crisis necessitating hospital admission (primary outcome) was reduced by 30.4% (mean 41.3 v. 59.3, P<0.001) when a home treatment team was available (intention-to-treat analysis). Regarding secondary outcomes, average overall treatment duration (hospital days + home treatment days) per patient (mean 50.4 v. 59.3, P = 0.969) and mean number of hospital admissions per patient (mean 1.86 v. 1.93, P = 0.885) did not differ statistically significantly between the experimental and control groups within 24 months after the index crisis. There were no significant between-group differences regarding clinical and social outcomes (Health of the Nation Outcome Scales: mean 9.9 v. 9.7, P = 0.652) or patient satisfaction with care (Perception of Care questionnaire: mean 0.78 v. 0.80, P = 0.242).

Home treatment services can reduce hospital use among severely ill patients in acute crises and seem to result in comparable clinical/social outcomes and patient satisfaction as standard in-patient care.

Natural disasters are increasing in frequency and impact; they cause widespread disruption and adversity throughout the world. The Canterbury earthquakes of 2010–2011 were devastating for the people of Christchurch, New Zealand. It is important to understand the impact of this disaster on the mental health of children and adolescents.

To report psychiatric medication use for children and adolescents following the Canterbury earthquakes.

Dispensing data from community pharmacies for the medication classes antidepressants, antipsychotics, anxiolytics, sedatives/hypnotics and methylphenidate are routinely recorded in a national database. Longitudinal data are available for residents of the Canterbury District Health Board (DHB) and nationally. We compared dispensing data for children and adolescents residing in Canterbury DHB with national dispensing data to assess the impact of the Canterbury earthquakes on psychotropic prescribing for children and adolescents.

After longer-term trends and population adjustments are considered, a subtle adverse effect of the Canterbury earthquakes on dispensing of antidepressants was detected. However, the Canterbury earthquakes were not associated with higher dispensing rates for antipsychotics, anxiolytics, sedatives/hypnotics or methylphenidate.

Mental disorders or psychological distress of a sufficient severity to result in treatment of children and adolescents with psychiatric medication were not substantially affected by the Canterbury earthquakes.

Understanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals.

Primary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia).

We found that 80% had stable NPI total ≥1, 50% had stable modest NPI total ≥12 and 25% had stable NPI total ≥24 scores. Very severe NPS (≥48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms.

We observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.

Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.

To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.

Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.

The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.

These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.

Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.

To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).

RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.

After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.

The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.

Diagnosing eating disorders can be difficult and few people with the disorder receive specialist services despite the associated high morbidity and mortality.

To examine the burden of eating disorders in the population in terms of incidence, comorbidities and survival.

We used linked electronic health records from general practitioner and hospital admissions in Wales, UK within the Secure Anonymised Information Linkage (SAIL) databank to investigate the incidence of new eating disorder diagnoses. We examined the frequency of comorbid diagnoses and prescribed medications in cases and controls in the 2 years before and 3 years after diagnosis, and performed a survival analysis.

A total of 15 558 people were diagnosed with eating disorders between 1990 and 2017. The incidence peaked at 24 per 100 000 people in 2003/04. People with eating disorders showed higher levels of other mental disorders (odds ratio 4.32, 95% CI 4.01–4.66) and external causes of morbidity and mortality (odds ratio 2.92, 95% CI 2.44–3.50). They had greater prescription of central nervous system drugs (odds ratio 3.15, 95% CI 2.97–3.33), gastrointestinal drugs (odds ratio 2.61, 95% CI 2.45–2.79) and dietetic drugs (odds ratio 2.42, 95% CI 2.24–2.62) before diagnosis. These excess diagnoses and prescriptions remained 3 years after diagnosis. Mortality was raised compared with controls for some eating disorders, particularly in females with anorexia nervosa.

Incidence of diagnosed eating disorders is relatively low in the population but there is a major longer term burden in morbidity and mortality to the individual.

Around 60 000 people in England live in mental health supported accommodation. There are three main types: residential care, supported housing and floating outreach. Supported housing and floating outreach aim to support service users in moving on to more independent accommodation within 2 years, but there has been little research investigating their effectiveness.

A 30-month prospective cohort study investigating outcomes for users of mental health supported accommodation.

We used random sampling, accounting for relevant geographical variation factors, to recruit 87 services (22 residential care, 35 supported housing and 30 floating outreach) and 619 service users (residential care 159, supported housing 251, floating outreach 209) across England. We contacted services every 3 months to investigate the proportion of service users who successfully moved on to more independent accommodation. Multilevel modelling was used to estimate how much of the outcome and cost variations were due to service type and quality, after accounting for service-user characteristics.

Overall 243/586 participants successfully moved on (residential care 15/146, supported housing 96/244, floating outreach 132/196). This was most likely for floating outreach service users (versus residential care: odds ratio 7.96, 95% CI 2.92–21.69, P < 0.001; versus supported housing: odds ratio 2.74, 95% CI 1.01–7.41, P < 0.001) and was associated with reduced costs of care and two aspects of service quality: promotion of human rights and recovery-based practice.

Most people do not move on from supported accommodation within the expected time frame. Greater focus on human rights and recovery-based practice may increase service effectiveness.

Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia.

To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort.

Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479).

In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort.

These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders.

Depression is a leading cause of disability, with older people particularly susceptible to poor outcomes.

To investigate whether the prevalence of depression and antidepressant use have changed across two decades in older people.

The Cognitive Function and Ageing Studies (CFAS I and CFAS II) are two English population-based cohort studies of older people aged ≥65 years, with baseline measurements for each cohort conducted two decades apart (between 1990 and 1993 and between 2008 and 2011). Depression was assessed by the Geriatric Mental State examination and diagnosed with the Automated Geriatric Examination for Computer-Assisted Taxonomy algorithm.

In CFAS I, 7635 people aged ≥65 years were interviewed, of whom 1457 were diagnostically assessed. In CFAS II, 7762 people were interviewed and diagnostically assessed. Age-standardised depression prevalence in CFAS II was 6.8% (95% CI 6.3–7.5%), representing a non-significant decline from CFAS I (risk ratio 0.82, 95% CI 0.64–1.07, P = 0.14). At the time of CFAS II, 10.7% of the population (95% CI 10.0–11.5%) were taking antidepressant medication, more than twice that of CFAS I (risk ratio 2.79, 95% CI 1.96–3.97, P < 0.0001). Among care home residents, depression prevalence was unchanged, but the use of antidepressants increased from 7.4% (95% CI 3.8–13.8%) to 29.2% (95% CI 22.6–36.7%).

A substantial increase in the proportion of the population reporting taking antidepressant medication is seen across two decades for people aged ≥65 years. However there was no evidence for a change in age-specific prevalence of depression.

Depression is one of the most common mental disorders in people with advanced cancer. Although cognitive–behavioural therapy (CBT) has been shown to be effective for depression in people with cancer, it is unclear whether this is the case for people with advanced cancer and depression.

We sought to determine whether CBT is more clinically effective than treatment as usual (TAU) for treating depression in people with advanced cancer (trial registration number ISRCTN07622709).

A multi-centre, parallel-group single-blind randomised controlled trial comparing TAU with CBT (plus TAU). Participants (n = 230) with advanced cancer and depression were randomly allocated to (a) up to 12 sessions of individual CBT or (b) TAU. The primary outcome measure was the Beck Depression Inventory-II (BDI-II). Secondary outcome measures included the Patient Health Questionnaire-9, the Eastern Cooperative Oncology Group Performance Status, and Satisfaction with Care.

Multilevel modelling, including complier-average intention-to-treat analysis, found no benefit of CBT. CBT delivery was proficient, but there was no treatment effect (−0.84, 95% CI −2.76 to 1.08) or effects for secondary measures. Exploratory subgroup analysis suggested an effect of CBT on the BDI-II in those widowed, divorced or separated (−7.21, 95% CI −11.15 to −3.28).

UK National Institute for Health and Care Excellence (NICE) guidelines recommend CBT for treating depression. Delivery of CBT through the Improving Access to Psychological Therapies (IAPT) programme has been advocated for long-term conditions such as cancer. Although it is feasible to deliver CBT through IAPT proficiently to people with advanced cancer, this is not clinically effective. CBT for people widowed, divorced or separated needs further exploration. Alternate models of CBT delivery may yield different results.

It is unclear what session frequency is most effective in cognitive–behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression.

Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression.

We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients to once or twice weekly sessions of CBT or IPT over 16–24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted.

Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates (n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00–2.18).

In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes.

Eating behaviours in childhood are considered as risk factors for eating disorder behaviours and diagnoses in adolescence. However, few longitudinal studies have examined this association.

We investigated associations between childhood eating behaviours during the first ten years of life and eating disorder behaviours (binge eating, purging, fasting and excessive exercise) and diagnoses (anorexia nervosa, binge eating disorder, purging disorder and bulimia nervosa) at 16 years.

Data on 4760 participants from the Avon Longitudinal Study of Parents and Children were included. Longitudinal trajectories of parent-rated childhood eating behaviours (8 time points, 1.3–9 years) were derived by latent class growth analyses. Eating disorder diagnoses were derived from self-reported, parent-reported and objectively measured anthropometric data at age 16 years. We estimated associations between childhood eating behaviours and eating disorder behaviours and diagnoses, using multivariable logistic regression models.

Childhood overeating was associated with increased risk of adolescent binge eating (risk difference, 7%; 95% CI 2 to 12) and binge eating disorder (risk difference, 1%; 95% CI 0.2 to 3). Persistent undereating was associated with higher anorexia nervosa risk in adolescent girls only (risk difference, 6%; 95% CI, 0 to 12). Persistent fussy eating was associated with greater anorexia nervosa risk (risk difference, 2%; 95% CI 0 to 4).

Our results suggest continuities of eating behaviours into eating disorders from early life to adolescence. It remains to be determined whether childhood eating behaviours are an early manifestation of a specific phenotype or whether the mechanisms underlying this continuity are more complex. Findings have the potential to inform preventative strategies for eating disorders.

Equitable access to mental healthcare is a priority for many countries. The National Health Service in England uses a weighted capitation formula to ensure that the geographical distribution of resources reflects need.

To produce a revised formula for estimating local need for secondary mental health, learning disability (intellectual disability) and psychological therapies services for adults in England.

We used demographic records for 43 751 535 adults registered with a primary care practitioner in England linked with service use, ethnicity, physical health diagnoses and type of household, from multiple data-sets. Using linear regression, we estimated the individual cost of care in 2015 as a function of individual- and area-level need and supply variables in 2013 and 2014. We sterilised the effects of the supply variables to obtain individual-need estimates. We aggregated these by general practitioner practice, age and gender to derive weights for the national capitation formula.

Higher costs were associated with: being 30–50 years old, compared with 20–24; being Irish, Black African, Black Caribbean or of mixed ethnicity, compared with White British; having been admitted for specific physical health conditions, including drug poisoning; living alone, in a care home or in a communal environment; and living in areas with a higher percentage of out-of-work benefit recipients and higher prevalence of severe mental illness. Longer distance from a provider was associated with lower cost.

The resulting needs weights were higher in more deprived areas and informed the distribution of some 12% (£9 bn in 2019/20) of the health budget allocated to local organisations for 2019/20 to 2023/24.