Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias.

We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access.

We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies.

Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1–27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5–30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11–2.21, P = 0.010).

Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports.

Exposure to parental suicide has been associated with increased risk for suicide and suicide attempts, although the strength of this association is unclear as evidence remains inconsistent.

To quantify this risk using meta-analysis and identify potential effect modifiers.

A systematic search in PubMed, PsycInfo and Embase databases to 2020 netted 3614 articles. Inclusion criteria were: observation of history of parental death by suicide, comparison with non-exposed populations and definition of suicide and suicide attempt according to standardised criteria. We focused on population-based studies. The primary outcome was the pooled relative risk (RR) for incidence of suicide attempt and suicide in offspring of a parent who died by suicide compared with offspring of two living parents. Additionally, we compared the RR for attempted and completed suicide after parental suicide with the RR for attempted and completed suicide after parental death by other causes.

Twenty studies met our inclusion criteria. Offspring exposed to parental suicide were more likely to die by suicide (RR = 2.97, 95% CI 2.50–3.53) and attempt suicide (RR = 1.76, 95% CI 1.58–1.96) than offspring of two living parents. Furthermore, their risk of dying by or attempting suicide was significantly higher compared with offspring bereaved by other causes of death.

The experience of losing a parent to suicide is a strong and independent risk factor for suicidal behaviour in offspring. Our findings highlight the need for prevention strategies, outreach programmes and support interventions that target suicide-related outcomes in the exposed population.

Exposure to maternal major depressive disorder (MDD) bears long-term negative consequences for children's well-being; to date, no research has examined how exposure at different stages of development differentially affects brain functioning.

Utilising a unique cohort followed from birth to preadolescence, we examined the effects of early versus later maternal MDD on default mode network (DMN) connectivity.

Maternal depression was assessed at birth and ages 6 months, 9 months, 6 years and 10 years, to form three groups: children of mothers with consistent depression from birth to 6 years of age, which resolved by 10 years of age; children of mothers without depression; and children of mothers who were diagnosed with MDD in late childhood. In preadolescence, we used magnetoencephalography and focused on theta rhythms, which characterise the developing brain.

Maternal MDD was associated with disrupted DMN connectivity in an exposure-specific manner. Early maternal MDD decreased child connectivity, presenting a profile typical of early trauma or chronic adversity. In contrast, later maternal MDD was linked with tighter connectivity, a pattern characteristic of adult depression. Aberrant DMN connectivity was predicted by intrusive mothering in infancy and lower mother–child reciprocity and child empathy in late childhood, highlighting the role of deficient caregiving and compromised socio-emotional competencies in DMN dysfunction.

The findings pinpoint the distinct effects of early versus later maternal MDD on the DMN, a core network sustaining self-related processes. Results emphasise that research on the influence of early adversity on the developing brain should consider the developmental stage in which the adversity occured.

Depression treatments are typically less effective for young people than for adults. However, treatments rarely target loneliness, which is a key risk factor in the onset, maintenance and development of depression.

This study evaluated the efficacy of a novel loneliness intervention, Groups 4 Health (G4H), relative to the best-practice treatment of cognitive–behavioural therapy (CBT) in reducing loneliness and depression over a 12-month period (Australian New Zealand Clinical Trial Registry: ACTRN12618000440224).

The study was a phase 3 randomised non-inferiority trial comparing G4H with dose-controlled group CBT. Participants were 174 people aged 15–25 years experiencing loneliness and clinically significant symptoms of depression, who were not in receipt of adjunct treatment. Participants were recruited from mental health services in Southeast Queensland, Australia. Randomisation was conducted using computer software. Follow-up assessments and statistical analyses were masked to allocation. Both interventions consisted of five 75 min group-based psychotherapy sessions. The primary outcomes were depression and loneliness, with a non-inferiority margin of 2.20 for depression.

The trial enrolled 174 participants between 24 April 2018 and 25 May 2019, with 84 in the G4H condition and 90 in the CBT condition. All randomised participants were included in the intention-to-treat analyses (n = 174). The pre–post effect sizes for depression were dG4H = −0.71 and dCBT = −0.91. For loneliness, they were dG4H = −1.07 and dCBT = −0.89. At 12-month follow-up, the absolute difference between groups on depression was 1.176 (95% CI −1.94 to 4.29) and on loneliness it was −0.679 (95% CI −1.43 to 0.07). No adverse effects were observed.

G4H was non-inferior to CBT for depression and showed a slight advantage over CBT for loneliness that emerged after treatment completion.

Long-term ‘not in education, employment or training’ (NEET) status is an important indicator of youth marginalisation.

To carry out a comprehensive overview of the associations between different psychiatric illnesses and long-term NEET status.

We used the register-based 1987 Finnish Birth Cohort study, which includes all live births in Finland during that year. The analyses comprised 55 273 individuals after exclusions for intellectual disability, death or emigration. We predicted that psychiatric disorders, diagnosed by specialist services between 1998 and 2007 when the cohort were 10–20 years of age, would be associated with subsequent long-term NEET (defined as NEET for at least 5 years between 2008 and 2015, when they were 20–28 years of age).

In total, 1438 individuals (2.6%) were long-term NEET during follow-up and the associations between long-term NEET and the 11 diagnostic categories we studied were statistically significant (P < 0.001). In multivariate models we included sociodemographic characteristics and upper secondary education as covariates, and the highest effect sizes, measured by odds ratios (OR) with 95% confidence intervals (CI), were found for psychosis (OR = 12.0, 95% CI 9.5–15.2) and autism spectrum disorder (OR = 17.3, 95% CI 11.5–26.0). If individuals had not successfully completed this education, 70.6% of those with autism spectrum disorder and 48.4% of those with psychosis were later long-term NEET.

Adolescents who receive treatment for psychiatric disorders, particularly autism spectrum disorder or psychosis, need support to access education and employment. This could help to prevent marginalisation in early adulthood.

Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention.

We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone.

A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16–25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation.

We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was −4.44 (95% CI −10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm.

We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.