With the development of evidence-based interventions for treatment of priority mental health conditions in humanitarian settings, it is important to establish the cost-effectiveness of such interventions to enable their scale-up.

To evaluate the cost-effectiveness of the Problem Management Plus (PM+) intervention compared with enhanced usual care (EUC) for common mental disorders in primary healthcare in Peshawar, Pakistan. Trial registration ACTRN12614001235695 (anzctr.org.au).

We randomly allocated 346 participants to either PM+ (n = 172) or EUC (n = 174). Effectiveness was measured using the Hospital Anxiety and Depression Scale (HADS) at 3 months post-intervention. Cost-effectiveness analysis was performed as incremental costs (measured in Pakistani rupees, PKR) per unit change in anxiety, depression and functioning scores.

The total cost of delivering PM+ per participant was estimated at PKR 16 967 (US$163.14) using an international trainer and supervisor, and PKR 3645 (US$35.04) employing a local trainer. The mean cost per unit score improvement in anxiety and depression symptoms on the HADS was PKR 2957 (95% CI 2262–4029) (US$28) with an international trainer/supervisor and PKR 588 (95% CI 434–820) (US$6) with a local trainer/supervisor. The mean incremental cost-effectiveness ratio (ICER) to successfully treat a case of depression (PHQ-9 ≥ 10) using an international supervisor was PKR 53 770 (95% CI 39 394–77 399) (US$517), compared with PKR 10 705 (95% CI 7731–15 627) (US$102.93) using a local supervisor.

The PM+ intervention was more effective but also more costly than EUC in reducing symptoms of anxiety, depression and improving functioning in adults impaired by psychological distress in a post-conflict setting of Pakistan.

Ethnic inequalities in health outcomes are often explained by socioeconomic status and concentrated poverty. However, ethnic disparities in psychotic experiences are not completely attenuated by these factors.

We investigated whether disparities are better explained by interactions between individual risk factors and place-based clustering of disadvantage, termed a syndemic.

We performed a cross-sectional survey of 3750 UK men, aged 18–34 years, oversampling Black and minority ethnic (BME) men nationally, together with men residing in London Borough of Hackney. Participants completed questionnaires covering psychiatric symptoms, substance misuse, crime and violence, and risky sexual health behaviours. We included five psychotic experiences and a categorical measure of psychosis based on the Psychosis Screening Questionnaire.

At national level, more Black men reported psychotic experiences but disparities disappeared following statistical adjustment for social position. However, large disparities for psychotic experiences in Hackney were not attenuated by adjustment for social factors in Black men (adjusted odds ratio, 3.24; 95% CI 2.14–4.91; P < 0.002), but were for South Asian men. A syndemic model of joint effects, adducing a four-component latent variable (psychotic experiences and anxiety, substance dependence, high-risk sexual behaviour and violence and criminality) showed synergy between components and explained persistent disparities in psychotic experiences. A further interaction confirmed area-level effects (Black ethnicity × Hackney residence, 0.834; P < 0.001).

Syndemic effects result in higher rates of non-affective psychosis among BME persons in certain inner-urban settings. Further research should investigate how syndemics raise levels of psychotic experiences and related health conditions in Black men in specific places with multiple deprivations.

Adolescent subthreshold emotional symptoms arise from impaired self-referential information-processing and approach–avoidance behaviour network integration, which compromises goal evaluation and pursuit strategies.

We investigated whether impairment of negative emotion (goal) reappraisal strategies (self-focussing and self-distancing) generates emotional symptoms (emotional disorders precursors).

Using functional magnetic resonance imaging and a triple-network model (default mode, executive control and salience), functional connectivity differences within and between networks, and their modulation by task and relationships with emotional symptoms were determined in healthy adolescent girls (N = 202) grouped by presence or absence of emotional symptoms.

The groups differed in spectral power distribution and in dorsal default mode network and right executive control network modulation when self-focussing and self-distancing, respectively. Girls without emotional symptoms had greater spectral power and less network modulation. Greater spectral power was associated with reduced emotional symptoms and less dorsal default mode network modulation when self-focussing.

The early phases of anxiety and depressive disorders in adolescence are marked by emotional symptoms that usually emerge in the context of negative life events. To contend with the negative effect of such events, a typical reappraisal strategy is to distance oneself and switch the focus of one's thinking. This brain-imaging study in adolescent girls prone to the development of emotional disorders has found functional changes in key neural networks that are involved in reappraisal and shown that this process is impaired. This is important because it provides an early indication of these common disorders and a potential target for psychological interventions.

According to the stress inoculation hypothesis, successfully navigating life stressors may improve one's ability to cope with subsequent stressors, thereby increasing psychiatric resilience.

Among individuals with no baseline history of post-traumatic stress disorder (PTSD) and/or major depressive disorder (MDD), to determine whether a history of a stressful life event protected participants against the development of PTSD and/or MDD after a natural disaster.

Analyses utilised data from a multiwave, prospective cohort study of adult Chilean primary care attendees (years 2003–2011; n = 1160). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument, and the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events. During the study (2010), the sixth most powerful earthquake on record struck Chile. One year later (2011), the CIDI was re-administered to assess post-disaster PTSD and/or MDD.

Marginal structural logistic regressions indicated that for every one-unit increase in the number of pre-disaster stressors, the odds of developing post-disaster PTSD or MDD increased (OR = 1.21, 95% CI 1.08–1.37, and OR = 1.16, 95% CI 1.06–1.27 respectively). When categorising pre-disaster stressors, individuals with four or more stressors (compared with no stressors) had higher odds of developing post-disaster PTSD (OR = 2.77, 95% CI 1.52–5.04), and a dose–response relationship between pre-disaster stressors and post-disaster MDD was found.

In contrast to the stress inoculation hypothesis, results indicated that experiencing multiple stressors increased the vulnerability to developing PTSD and/or MDD after a natural disaster. Increased knowledge regarding the individual variations of these disorders is essential to inform targeted mental health interventions after a natural disaster, especially in under-studied populations.

It has been hypothesised that refugees have an increased risk of suicide.

To investigate whether risk of suicide is higher among refugees compared with non-refugee migrants from the same areas of origin and with the Swedish-born population, and to examine whether suicide rates among migrants converge to the Swedish-born population over time.

A population-based cohort design using linked national registers to follow 1 457 898 people born between 1 January 1970 and 31 December 1984, classified by migrant status as refugees, non-refugee migrants or Swedish-born. Participants were followed from their 16th birthday or date of arrival in Sweden until death, emigration or 31 December 2015, whichever came first. Cox regression models estimated adjusted hazard ratios for suicide by migrant status, controlling for age, gender, region of origin and income.

There were no significant differences in suicide risk between refugee and non-refugee migrants (hazard ratio 1.28, 95% CI 0.93–1.76) and both groups had a lower risk of suicide than Swedish born. During their first 5 years in Sweden no migrants died by suicide; however, after 21–31 years their suicide risk was equivalent to the Swedish-born population (hazard ratio 0.94, 95% CI 0.79–1.22). After adjustment for income this risk was significantly lower for migrants than the Swedish-born population.

Being a refugee was not an additional risk factor for suicide. Our findings regarding temporal changes in suicide risk suggest that acculturation and socioeconomic deprivation may account for a convergence of suicide risk between migrants and the host population over time.

None.

Little is known about long-term employment outcomes for patients with first-episode schizophrenia-spectrum (FES) disorders who received early intervention services.

We compared the 10-year employment trajectory of patients with FES who received early intervention services with those who received standard care. Factors differentiating the employment trajectories were explored.

Patients with FES (N = 145) who received early intervention services in Hong Kong between 1 July 2001 and 30 June 2002 were matched with those who entered standard care 1 year previously. We used hierarchical clustering analysis to explore the 10-year employment clusters for both groups. We used the mixed model test to compare cluster memberships and piecewise regression analysis to compare the employment trajectories of the two groups.

There were significantly more patients who received the early intervention service in the good employment cluster (early intervention: N = 98 [67.6%]; standard care: N = 76 [52.4%]; P = 0.009). In the poor employment cluster, there was a significant difference in the longitudinal pattern between early intervention and standard care for years 1–5 (P < 0.0001). The number of relapses during the first 3 years, months of full-time employment during the first year and years of education were significant in differentiating the clusters of the early intervention group.

Results suggest there was an overall long-term benefit of early intervention services on employment. However, the benefit was not sustained for all patients. Personalisation of the duration of the early intervention service with a focus on relapse prevention and early vocational reintegration should be considered for service enhancement.

Depression and cardiovascular diseases (CVDs) are common diseases and associated in a bidirectional manner.

To examine whether a bidirectional association between CVD and depression could be explained by shared risk factors, misclassification of disease measures or non-response.

A total of 10 population-based cohorts including 93 076 men and women (mean age 54.4 years, s.d. = 9.2) and an additional 10 510 men (mean age 51.2 years, s.d. = 0.3) were followed for subsequent depression, ischaemic heart disease (IHD) and stroke in the Danish National Patient Registry from health examinations between 1982 and 2015 and until end of follow-up in 2017–2018. Exposures were physicians’ diagnoses of IHD, stroke, depression or self-reported chest pain, depression, use of antidepressant medication and the Major Depression Inventory at the time of study entry in the Metropolit study. Associations were analysed using Cox proportional hazard regression with disease as time-dependent variables.

IHD and stroke were associated with subsequent depression (hazard ratio (HR) for IHD: 1.79, 95% CI 1.43–2.23 and HR for stroke: 2.62, 95% CI 2.09–3.29) and the associations were present in both men and women. Adjustment for the shared risk factors socioeconomic status, lifestyle, body mass index, statin use and serum lipids did not change the risk estimates. Furthermore, depression was associated with higher risk of subsequent IHD (HR = 1.63, 95% CI 1.36–1.95) and stroke (HR = 1.94, 95% CI 1.63–2.30). The associations were also present when the analyses were based on self-reported disease measures or restricted to include non-responders.

The bidirectional association between CVD and depression was not explained by shared risk factors, misclassification or non-response.

Internationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI).

To explore the relationship between IPV exposure and mental illness in a UK population.

We designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes.

At baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52–2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58–2.97). Anxiety (aIRR 1.99, 95% CI 1.80–2.20), depression (aIRR 3.05, 95% CI 2.81–3.31) and SMI (aIRR 3.08, 95% CI 2.19–4.32) were all associated with exposure to IPV.

IPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.

Most research on mortality in people with severe psychiatric disorders has focused on natural causes of death. Little is known about trauma-related mortality, although bipolar disorder and schizophrenia have been associated with increased risk of self-administered injury and road accidents.

To determine if 30-day in-patient mortality from traumatic injury was increased in people with bipolar disorder and schizophrenia compared with those without psychiatric disorders.

A French national 2016 database of 144 058 hospital admissions for trauma was explored. Patients with bipolar disorder and schizophrenia were selected and matched with mentally healthy controls in a 1:3 ratio according to age, gender, social deprivation and region of residence. We collected the following data: sociodemographic characteristics, comorbidities, trauma severity characteristics and trauma circumstances. Study outcome was 30-day in-patient mortality.

The study included 1059 people with bipolar disorder, 1575 people with schizophrenia and their respective controls (n = 3177 and n = 4725). The 30-day mortality was 5.7% in bipolar disorder, 5.1% in schizophrenia and 3.3 and 3.8% in the controls, respectively. Only bipolar disorder was associated with increased mortality in univariate analyses. This association remained significant after adjustment for sociodemographic characteristics and comorbidities but not after adjustment for trauma severity. Self-administered injuries were associated with increased mortality independent of the presence of a psychiatric diagnosis.

Patients with bipolar disorder are at higher risk of 30-day mortality, probably through increased trauma severity. A self-administered injury is predictive of a poor survival prognosis regardless of psychiatric diagnosis.

Although clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided.

To compare the real-world effectiveness of antipsychotics after clozapine cessation.

From Finnish registry data (1995–2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences.

Compared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40–0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48–0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53–0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27–0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43–0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61–0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09–0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17–0.40; P < 0.0001).

Clozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.

Psychiatric disorders are associated with increased risk of ischaemic heart disease (IHD) and stroke, but it is not known whether the associations or the role of sociodemographic factors have changed over time.

To investigate the association between psychiatric disorders and IHD and stroke, by time period and sociodemographic factors.

We used Scottish population-based records from 1991 to 2015 to create retrospective cohorts with a hospital record for psychiatric disorders of interest (schizophrenia, bipolar disorder or depression) or no record of hospital admission for mental illness. We estimated incidence and relative risks of IHD and stroke in people with versus without psychiatric disorders by calendar year, age, gender and area-based deprivation level.

In all cohorts, incidence of IHD (645 393 events) and stroke (276 073 events) decreased over time, but relative risks decreased for depression only. In 2015, at the mean age at event onset, relative risks were 2- to 2.5-fold higher in people with versus without a psychiatric disorder. Age at incidence of outcome differed by cohort, gender and socioeconomic status. Relative but not absolute risks were generally higher in women than men. Increasing deprivation conveys a greater absolute risk of IHD for people with bipolar disorder or depression.

Despite declines in absolute rates of IHD and stroke, relative risks remain high in those with versus without psychiatric disorders. Cardiovascular disease monitoring and prevention approaches may need to be tailored by psychiatric disorder and cardiovascular outcome, and be targeted, for example, by age and deprivation level.

Positive social relationships are known to mitigate the negative effects of stress on mental health. However, the direction of association between social resources and mental health remains unclear, and it is not known whether higher than average levels of social resources confer additional benefits, in the short and longer term.

To investigate the concurrent and longitudinal contribution of higher levels of social resources in reducing the risk of mental health symptoms after exposure to stress at age 45, and to identify life-course precursors of mid-life social resources.

The National Child Development Study (NCDS) is a prospective birth cohort of over 17 000 births in 1958. We tested concurrent and longitudinal associations between different levels of social resources at age 45 and mental health symptoms among individuals exposed to stress and verified whether prior mental health symptoms (age 42) explained these associations. We also tested a range of child, family and adult precursors of mid-life social resources.

Higher than average levels of social resources were required to confer benefits to mental health among individuals exposed to high stress levels, both concurrently at age 45 and in the longer term at age 50. In general, these associations were not attributable to prior mental health symptoms. Key predictors of mid-life social resources included evidence of early sociability.

Having a broad network of social ties and better personal support helps individuals withstand exposure to higher levels of stress. Given that sociable children had better mid-life social resources, early intervention may benefit individuals' social resources later in life.

Residential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear.

We used a population-based case–cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10–14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder.

Information on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981–1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses.

PRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00–1.16; and odds ratio 1.10, 95% CI 1.04–1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5–11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08–1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92–4.86; three or more moves and bipolar disorder).

Associations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.

Awareness materials featuring ways of coping with suicidal ideation can reduce suicidal ideation, the so-called Papageno effect. All of the previous experimental studies on this subject have been conducted with individuals not at risk of suicide.

To assess effects of suicide awareness materials in a sample of individuals with recent suicidal ideation. Trial registration: German Clinical Trial Registry ID number DRKS00013613.

Adults (n = 266) with recent self-reported suicidal ideation or attempt were randomised to read an educative article featuring a lay individual with personal experience of suicidality (n = 86), a similar article featuring a mental health expert (n = 90), or an unrelated article (n = 90) in a double-blind online randomised controlled trial. Questionnaire data were collected before (T1) and immediately after exposure (T2) as well as 1 week later (study end-point, T3) and analysed with linear mixed models. The primary outcome was suicide risk as assessed using the Survival and Coping Beliefs subscale of the Reasons for Living Inventory (RFLI); secondary outcomes were suicide-prevention knowledge and mood.

There was an immediate beneficial effect on suicide risk in the intervention group exposed to the message delivered by the individual with personal experience (group 1) as compared with the control group that was maintained until the study end-point (study end-point: RFLI score mean difference from baseline within group 1 MD = −0.36 (95% CI −0.66 to −0.06), mean difference compared with control group MD = −0.71 (95% CI −1.27 to −0.14); d = −0.18). The effect was particularly pronounced for individuals with recent suicide attempt (RFLI score at T3, compared with control group: MD = −1.55 (95% CI −2.52 to −0.57); d = −0.23). Participants in this group also showed increased prevention-related knowledge compared with the control group.

Individuals with a recent suicide attempt appear to benefit from a printed narrative of positive coping with suicidal ideation. The intervention materials do not increase short-term suicide risk.

Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.

This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.

Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.

Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.

Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity.

Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder.

CAPsy is population-based first-episode psychosis case–control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments.

We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence.

Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.

Previous literature has demonstrated a strong association between cigarette smoking, suicidal ideation and suicide attempts. This association has not previously been examined in a causal inference framework and could have important implications for suicide prevention strategies.

We aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation analyses.

First, in the UK Biobank, we calculated observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation to explore the relationship between smoking and suicide attempts and ideation, using genetic variants as instruments to reduce bias from residual confounding and reverse causation.

Our observational analysis showed a relationship between smoking behaviour, suicidal ideation and attempts, particularly between smoking initiation and suicide attempts (odds ratio, 2.07; 95% CI 1.91–2.26; P < 0.001). The Mendelian randomisation analysis and single-nucleotide polymorphism analysis, however, did not support this (odds ratio for lifetime smoking on suicidal ideation, 0.050; 95% CI −0.027 to 0.127; odds ratio on suicide attempts, 0.053; 95% CI, −0.003 to 0.110). Despite past literature showing a positive dose-response relationship, our results showed no clear evidence for a causal effect of smoking on suicidal ideation or attempts.

This was the first Mendelian randomisation study to explore the effect of smoking on suicidal ideation and attempts. Our results suggest that, despite observed associations, there is no clear evidence for a causal effect.

The general understanding of the ‘vulnerability–stress model’ of mental disorders neglects the modifying impact of resilience-increasing factors such as coping ability.

Probing a conceptual framework integrating both adverse events and coping factors in an extended ‘vulnerability–stress–coping model’ of mental disorders, the effects of functional neuropeptide S receptor gene (NPSR1) variation (G), early adversity (E) and coping factors (C) on anxiety were addressed in a three-dimensional G × E × C model.

In two independent samples of healthy probands (discovery: n = 1403; replication: n = 630), the interaction of NPSR1 rs324981, childhood trauma (Childhood Trauma Questionnaire, CTQ) and general self-efficacy as a measure of coping ability (General Self-Efficacy Scale, GSE) on trait anxiety (State-Trait Anxiety Inventory) was investigated via hierarchical multiple regression analyses.

In both samples, trait anxiety differed as a function of NPSR1 genotype, CTQ and GSE score (discovery: β = 0.129, P = 3.938 × 10−8; replication: β = 0.102, P = 0.020). In A allele carriers, the relationship between childhood trauma and anxiety was moderated by general self-efficacy: higher self-efficacy and childhood trauma resulted in low anxiety scores, and lower self-efficacy and childhood trauma in higher anxiety levels. In turn, TT homozygotes displayed increased anxiety as a function of childhood adversity unaffected by general self-efficacy.

Functional NPSR1 variation and childhood trauma are suggested as prime moderators in the vulnerability–stress model of anxiety, further modified by the protective effect of self-efficacy. This G × E × C approach – introducing coping as an additional dimension further shaping a G × E risk constellation, thus suggesting a three-dimensional ‘vulnerability–stress–coping model’ of mental disorders – might inform targeted preventive or therapeutic interventions strengthening coping ability to promote resilient functioning.

Heart disease is the leading cause of death in schizophrenia. However, there has been little research directly examining cardiac function in schizophrenia.

To investigate cardiac structure and function in individuals with schizophrenia using cardiac magnetic resonance imaging (CMR) after excluding medical and metabolic comorbidity.

In total, 80 participants underwent CMR to determine biventricular volumes and function and measures of blood pressure, physical activity and glycated haemoglobin levels. Individuals with schizophrenia (‘patients’) and controls were matched for age, gender, ethnicity and body surface area.

Patients had significantly smaller indexed left ventricular (LV) end-diastolic volume (effect size d = −0.82, P = 0.001), LV end-systolic volume (d = −0.58, P = 0.02), LV stroke volume (d = −0.85, P = 0.001), right ventricular (RV) end-diastolic volume (d = −0.79, P = 0.002), RV end-systolic volume (d = −0.58, P = 0.02), and RV stroke volume (d = −0.87, P = 0.001) but unaltered ejection fractions relative to controls. LV concentricity (d = 0.73, P = 0.003) and septal thickness (d = 1.13, P < 0.001) were significantly larger in the patients. Mean concentricity in patients was above the reference range. The findings were largely unchanged after adjusting for smoking and/or exercise levels and were independent of medication dose and duration.

Individuals with schizophrenia show evidence of concentric cardiac remodelling compared with healthy controls of a similar age, gender, ethnicity, body surface area and blood pressure, and independent of smoking and activity levels. This could be contributing to the excess cardiovascular mortality observed in schizophrenia. Future studies should investigate the contribution of antipsychotic medication to these changes.