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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. [ABSTRACT FROM AUTHOR]

Objective: According to the gene-environment interaction model the pathogenesis of psychosis relies on an adverse neuro-socio-developmental pathway. Perinatal stress represents an important risk factor for the development of psychosis because of the increasingly evident interference with socio-neuro-development in the earlier phases of life. We aim to investigate the correlation of perinatal risk factors with the onset of psychosis with a case–control–incidence study. Results: Patients (and their mothers) were eligible if they presented with first-episode psychosis at the Bologna West Community Mental Health Centre (Bo-West CMHC) between 2002 and 2012. The Bo-West CMHC serves a catchment area of about 200,000 people. The controls were recruited in the same catchment area and study period. 42 patients, 26 controls and their mothers were included. We collected the history of peri-natal stress and calculated crude and adjusted Odds Ratios for onset of first-episode psychosis. Adjusted logistic regression showed that psychosis onset was significantly associated with stressful situations during pregnancy, lower level of maternal physical health before or during pregnancy, use of anti-inflammatory drugs during pregnancy, and low level of maternal education. The results of our study suggest that stress during perinatal period increases the risk of developing psychosis. [ABSTRACT FROM AUTHOR]

A poor use of mental health services has been described in immigrants. We compared the sociodemographic, clinical and treatment features of immigrants and natives attending a Community Mental Health Centre (CMHC). 191 immigrants and 191 randomly selected natives applying to the Borgomanero CMHC between 1 January 2003 and 31 August 2013 were compared. Our sample consisted mainly of the so-called 'economic' immigrant. Adjustment disorders and reaction to stress were the most frequent diagnoses; in most cases symptoms onset occurred after migration. Although treatment features overlapped in the two groups (duration, number of contacts), immigrants showed a higher frequency of treatment dropout. While it is necessary to improve access to mental health services for immigrants, for the 'economic' immigrant it may be more important to focus on establishing a therapeutic relationship that can be experienced as reliable and trustworthy. The finding of similar pathways to access the CMHC in natives and immigrants is encouraging. [ABSTRACT FROM AUTHOR]

Purpose: To describe antidepressant (AD) use in the Emilia-Romagna Region (Italy) and to evaluate adherence to treatment with selective serotonin receptor inhibitors or selective noradrenaline receptor inhibitors (SSRI-SNRI). Methods: Reimbursed prescriptions of AD were retrieved from the Emilia-Romagna Regional Health Authority Database. The overall AD consumption from the 2006–2011 period was expressed in terms of prevalence and amount of use. Adherence to treatment was assessed in a cohort of patients who received SSRI-SNRI, and was followed throughout a 6-month period from the start of each treatment episode. Adherence was considered according to three parameters: duration of treatment ≥ 120 days, prescription coverage ≥ 80 %, and gaps between prescriptions < 3 months. Determinants of non-adherent regimen, including sociodemographic and clinical variables, were identified by multivariate logistic regression by calculating adjusted Odds Ratio (adjOR) and the relevant 95 % confidence interval (95CI). Results: From 2006 to 2011, the prevalence of use of AD increased by 5 % (from 86 to 90 per 1,000 inhabitants) and the amount of antidepressant consumption increased by 20 % (from 43 to 51 defined daily dose per thousand inhabitants per day [DDD/TID]), with a 14 % rise in the intensity of drug use (from 182 to 208 DDD per patient). Out of 347,615 SSRI-SNRI treatment episodes, only 23.8 % were adherent. Comorbidity (adjOR:0.69; 95CI:0.67–0.72) and recurrence of AD treatment in the previous year (0.91; 0.89–0.92) were associated with better adherence. Moreover, patients treated with duloxetine (0.58; 0.55–0.60), escitalopram (0.64; 0.62–0.66) or sertraline (0.65; 0.64–0.67) showed better adherence in comparison with paroxetine. Conclusions: Clinical variables resulting in improved adherence seem to identify patients with more severe disorders and who actually need a pharmacological approach, whereas differences in adherence among ADs could in part be caused by channeling and sponsorship bias. Initiatives addressed at improving cooperation between primary care and psychiatrists could decrease AD prescription for cases of sub-threshold or mild depression that easily drop out because of rapid symptom relief or side effects. [ABSTRACT FROM AUTHOR]

Abstract: Trial design: This was a multicenter cluster-randomized controlled trial. Participants: A total of 227 patients ≥18 years old with a new onset of depressive symptoms who screened positive on the first two items of the Patient Health Questionnaire-9 (PHQ-9) were recruited by primary care physicians (PCPs) of eight health districts of three Italian regions from September 2009 to June 2011. Intervention: PCPs of the intervention group received a specific collaborative care program including 2 days of intensive training, implementation of a stepped care protocol, depression management toolkit and scheduled meetings with a dedicated consultant psychiatrist. Objective: The objective was to determine whether a collaborative care program for depression management in primary care leads to higher remission rate than usual PCP care. Outcomes: Outcome was clinical remission as expressed on PHQ-9 <5 at 3 months. Randomization: An independent researcher used computer-generated randomization to assign involved primary care groups to the two alternative arms. Blinding: PCPs and research personnel were not blinded. Results: The 223 PCPs enrolled recruited 227 patients (128 in collaborative care arm, 99 in the usual care arm). At 3 months (n=210), the proportion of patients who achieved remission was higher, though the difference was not statistically significant, in the collaborative care group. The effect size was of 0.11. When considering only patients with minor/major depression, collaborative care appeared to be more effective than usual care (P=.015). Conclusions: The present intervention for managing depression in primary care, designed to be applicable to the Italian context, appears to be effective and feasible. [Copyright &y& Elsevier]

Objectives: To establish whether the risk of psychotic disorders in cannabis users changes with time following cannabis cessation using data from the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia (EU-GEI) case-control study., Methods: The EU-GEI case-control study collected data from first episode psychosis patients and population controls across sites in Europe and Brazil between May 2010 and April 2015. Adjusted logistic regressions were applied to examine whether the odd of psychosis case status changed: (1) with time following cannabis cessation and (2) across different cannabis use groups., Results: Psychosis risk declined following cessation of cannabis use (β = -0.002; 95% CI -0.004 to 0.000; P  = 0.067). When accounting for duration of use, this effect remained (β = -0.003; 95% CI -0.005 to -0.001; P  = 0.013). However, in models adjusting for frequency and potency of use the result was not significant. Analysis of different cannabis use groups indicated that ex-users who stopped 1 to 4 weeks previously had the highest risk for psychotic disorder compared to never users (OR = 6.89; 95% CI 3.91-12.14; P  < 0.001); risk declined for those who stopped 5 to 12 weeks previously (OR = 2.70; 95% CI 1.73-4.21; P  < 0.001) and 13 to 36 weeks previously (OR = 1.53; 95% CI 1.00-2.33; P  = 0.050). Ex-users who stopped 37 to 96 weeks (OR = 1.01; 95% CI 0.66-1.57; P  = 0.949), 97 to 180 weeks (OR = 0.73; 95% CI 0.45-1.19; P  = 0.204), and 181 weeks previously or more (OR = 1.18; 95% CI 0.76-1.83; P  = 0.456) had similar psychosis risk to those who had never-used cannabis., Conclusion: Risk of psychotic disorder appears to decline with time following cannabis cessation, receding to that of those who have never used cannabis after 37 weeks or more of abstinence. Although, preliminary results suggest that frequent users of high potency types of cannabis might maintain an elevated risk compared to never users even when abstaining for longer than 181 weeks., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MDF reports personal fees from Janssen, outside the submitted work. RMM reports personal fees from Janssen, Lundbeck, Sunovion, and Otsuka, outside of the submitted work. CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. The other authors have no conflicts of interest to declare.

Objectives: Pathways to Care (PtC) are useful indicators of how patients access mental healthcare, especially in the context of first-episode psychosis (FEP). We explored how PtC: source of referral, is associated with patients' characteristics and clinical presentation and assessed the cross-country differences of the PtC predictors between South London and Bologna., Methods: This study included 427 FEP individuals in the context of the European Union Gene-Environment Interactions (EU-GEI) study. We performed multinomial logistic regression to test the associations between our outcome variables (PtC) and the independent study variables., Results: In London, patients were more likely to be referred by GPs or specialists, while in Bologna, most patients followed the emergency route. Despite the study centre differences, older patients were more likely to be referred by GPs; patients referred informally and via specialist services were more likely to be single. Compared with emergency referrals, patients referred by GPs and specialists experienced a longer DUP. We found insufficient evidence of an association between symptoms profile and PtC., Conclusions: PtC characteristics of FEP patients were associated with several sociodemographic and DUP in both study centres. Our results highlight the importance of social networks and social services and public engagement, and public health initiatives (such as psychoeducation in schools and leisure centres) in easing help-seeking behaviours., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified., Methods: We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of polygenic risk scores for schizophrenia, bipolar disorder, and depression (PRS-SZ, PRS-BD, and PRS-D) with schizophrenia-spectrum disorder and affective psychosis differed when participants were stratified by exposure to specific environmental factors. Secondly, regression models including each PRS and polyenvironmental measures, including migration, paternal age, childhood adversity and frequent cannabis use, were run to test potential polygenic by polyenvironment interactions., Results: In schizophrenia-spectrum disorder vs controls comparison, PRS-SZ was the strongest genetic predictor, having a nominally larger effect in nonexposed to strong environmental factors such as frequent cannabis use (unexposed vs exposed OR 2.43 and 1.35, respectively) and childhood adversity (3.04 vs 1.74). In affective psychosis vs controls, the relative contribution of PRS-D appeared to be stronger in those exposed to environmental risk. No evidence of interaction was found between any PRS with polyenvironmental score., Conclusions: Our study supports an independent role of genetic liability and polyenvironmental risk for psychosis, consistent with the liability threshold model. Whereas schizophrenia-spectrum disorders seem to be mostly associated with polygenic risk for schizophrenia, having an additive effect with well-replicated environmental factors, affective psychosis seems to be a product of cumulative environmental insults alongside a higher genetic liability for affective disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis., Methods: Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use., Results: In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08-8.43, p = 3.21 × 10 -10 ). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use., Conclusions: Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

Background: Urbanicity is a well-established risk factor for psychosis. Our recent multi-national study found an association between urbanicity and clinical psychosis in Northern Europe but not in Southern Europe. In this study, we hypothesized that the effect of current urbanicity on variation of schizotypy would be greater in North-western Europe countries than in Southern Europe ones., Methods: We recruited 1080 individuals representative of the populations aged 18-64 of 14 different sites within 5 countries, classified as either North-western Europe (England, France, and The Netherlands) with Southern Europe (Spain and Italy). Our main outcome was schizotypy, assessed through the Structured Interview for Schizotypy-Revised. Our main exposure was current urbanicity, operationalized as local population density. A priori confounders were age, sex, ethnic minority status, childhood maltreatment, and social capital. Schizotypy variation was assessed using multi-level regression analysis. To test the differential effect of urbanicity between North-western and Southern European, we added an interaction term between population density and region of recruitment., Results: Population density was associated with schizotypy (β = 0.248,95%CI = 0.122-0.375;p < 0.001). The addition of the interaction term improved the model fit (likelihood test ratio:χ 2  = 6.85; p = 0.009). The effect of urbanicity on schizotypy was substantially stronger in North-western Europe (β = 0.620,95%CI = 0.362-0.877;p < 0.001) compared with Southern Europe (β = 0.190,95%CI = 0.083-0.297;p = 0.001)., Conclusions: The association between urbanicity and both subclinical schizotypy and clinical psychosis, rather than being universal, is context-specific. Considering that urbanization is a rapid and global process, further research is needed to disentangle the specific factors underlying this relationship., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity., (© 2024. The Author(s).)

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1 gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCU gene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure., (© 2024. The Author(s).)

Even during the third wave of the COVID-19 pandemic health professionals were facing mental health challenges. The aim of this study was to examine the mental health of doctors, nurses and other professional groups in Europe and to identify differences between the professional groups. We conducted a cross-sectional online survey in 8 European countries. We asked for demographic data, whether the participants were exposed to COVID-19 at work, for main information sources about the pandemic, the Depression Anxiety Stress Scales (DASS-21), and major stressors. A MANCOVA was carried out to find predictors of mental health among health care professionals. The sample (N = 1398) consisted of 237 physicians, 459 nurses, and 351 other healthcare professionals and 351 non-medical professionals with no direct involvement in patient care. The mean mental health of all groups was affected to a mild degree. Major predictors for depression and anxiety were the profession group with higher scores especially in the group of the nurses and working directly with COVID-patients. In the third wave of the COVID-19 pandemic, the psychological burden on health professionals has remained high, with being nurse and working directly with COVID19 patients being particular risk factors for mental distress. We found as a main result that nurses scored significantly higher on depression and anxiety than practitioners., (© 2024. The Author(s).)

Background and Hypothesis: Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings., Study Design: We used incidence data in people aged 18-64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group., Study Results: Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61-0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55-0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02-2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings., Conclusions: Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)