Background Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. Methods We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ⁹-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. Findings Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3•2, 95% CI 2•2-4•1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4•8, 2•5-6•3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12•2% (95% CI 3•0-16•1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30•3% (15•2-40•0) in London and 50•3% (27•4-66•0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0•7; p=0•0286) and daily use (r = 0•8; p=0•0109). Interpretation Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.

This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.

Summary Background The last comprehensive systematic review of the incidence of psychotic disorders was published in 2004. New epidemiological data from different settings now permit a broader understanding of global variation. We examined the variation in psychosis by demographic characteristics and study method. Methods For this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, PsycINFO, and bibliographies, and directly contacted first authors. We sought to obtain citations of original research published between Jan 1, 2002, and Dec 31, 2017, on incidence of non-organic adult-onset psychotic disorder. We included papers that were published or in grey literature and had no language restrictions. Data were extracted from published reports, where possible, by sex, age, and ethnic group. Quality of yield was assessed. Data were assessed using univariable random-effects meta-analysis and meta-regression. We registered our systematic review on PROSPERO, number CRD42018086800. Findings From 56 721 records identified, 177 met inclusion criteria. The pooled incidence of all psychotic disorders was 26·6 per 100 000 person-years (95% CI 22·0–31·7). Heterogeneity was high ( I 2 ≥98·5%). Men were at higher risk of all psychotic disorders (incidence rate ratio 1·44 [1·27–1·62]) and non-affective disorders (1·60 [1·44–1·77]) than women, but not affective psychotic disorders (0·87 [0·75–1·00]). Ethnic minorities were also at excess risk of all psychotic disorders (1·75 [1·53–2·00]), including non-affective disorders (1·71 [1·40–2·09]). Meta-regression revealed that population registers reported higher rates of non-affective disorders (9·64 [2·72–31·82]), schizophrenia (2·51 [1·24–5·21]), and bipolar disorder (4·53 [2·41–8·51]) than first contact study designs. Interpretation We found marked variation in incidence of psychotic disorders by personal characteristics and place. Some geographical variation could be partially explained by differences in case ascertainment methods. Funding None.

BackgroundThe value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.MethodThis study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.ResultsA bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.ConclusionsOur results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

BackgroundConcerns about adverse effects on patient satisfaction may be an important obstacle to attempts to curtail antibiotic prescribing. AimTo determine the relationship between antibiotic prescribing in general practice and reported patient satisfaction. Design and settingRetrospective cross-sectional study of general practices in England. Method ResultsThe final dataset consisted of 7800 (95.5%) practices. A total of 33.7 million antibiotic prescriptions were issued to a registered population of 53.8 million patients. Antibiotic prescribing volume was a significant positive predictor of all 'doctor satisfaction' and 'practice satisfaction' scores in the GPPS, and was the strongest predictor of overall satisfaction out of 13 prescribing variables. A theoretical 25% reduction in antibiotic prescribing volume would be associated with 0.5-1.0% lower patient satisfaction scores, a drop of 3-6 centile points in national satisfaction ranking. ConclusionPatients were less satisfied in practices with frugal antibiotic prescribing. A cautious approach to antibiotic prescribing may require a trade-off in terms of patient satisfaction.

Background Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns. Methods We used case–control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20–F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data. Results Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69–2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31–1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22–1.89) and linguistic distance (OR 1.22, 95% CI 0.95–1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively. Conclusion Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.

Purpose The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case-control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions This resource constitutes the largest and most extensive incidence and case-control study of psychosis ever conducted. Keywords Case-control • Environment-environment interactions • EU-GEI • First-episode psychosis • Gene-environment interactions • Incidence The members of the EU-GEI WP2 Group are listed in Acknowledgements.

Background Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. Method We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. Results In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. Conclusions Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.