0000000000225114
AUTHOR
Andrei Szöke
The EUropean Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI)
Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909
Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study.
Background\ud The 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.\ud \ud Method\ud This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks st…
Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis
The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme.
Migration history and risk of psychosis: results from the multinational EU-GEI study.
The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project was funded by grant agreement Health-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework programme.
Perceived major experiences of discrimination, ethnic group, and risk of psychosis in a six-country case-control study
AbstractBackgroundPerceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.MethodsWe used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-…
Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls
AbstractBackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the association…
A Multilevel Functional Study of aSNAP25At-Risk Variant for Bipolar Disorder and Schizophrenia
The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant inSNAP25,rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combinedin vitroandin vivoapproaches in humans to understand the functional impact of the at-risk allele. Thus, we showedin vi…
Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Duration of untreated psychosis in first-episode psychosis is not associated with common genetic variants for major psychiatric conditions: results from the multi-center EU-GEI Study
The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010–241909 (Project EU-GEI).
The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study
Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom di…
Pre-training inter-rater reliability of clinical instruments in an international psychosis research project.
International audience
Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study
AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on J…
Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study
Importance: Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives: To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants: An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catch…
Premorbid Adjustment and IQ in Patients With First-Episode Psychosis: A Multisite Case-Control Study of Their Relationship With Cannabis Use
Abstract Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic p…
The independent and combined influence of schizophrenia polygenic risk score and heavy cannabis use on risk for psychotic disorder: A case-control analysis from the EUGEI study.
Background: Some recent studies have challenged the direction of causality for the association between cannabis use and psychotic disorder, suggesting that cannabis use initiation is explained by common genetic variants associated with risk of schizophrenia. We used data from the European Union Gene-Environment Interaction consortium (EUGEI) case-control study to test for the independent and combined effect of heavy cannabis use, and of Schizophrenia Polygenic risk score (SZ PRS), on risk for psychotic disorder. Methods: Genome-wide data were obtained from 492 first episode psychosis patients (FEPp) and from 787 controls of European Ancestry, and used to generate SZ PRS from the summary res…
Jumping to conclusions, general intelligence, and psychosis liability: Findings from the multi-centre EU-GEI case-control study
This study was funded by the Medical Research Council, the European Community’s Seventh Framework Program grant [agreement HEALTH-F2-2009-241909 (Project EU-GEI)], São Paulo Research Foundation (grant 2012/0417-0), the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London, the NIHR BRC at University College London and the Wellcome Trust (grant 101272/Z/12/Z).
Social disadvantage, linguistic distance, ethnic minority status and first-episode psychosis: Results from the EU-GEI case-control study
The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project was funded by grant agreement Health-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework programme. The Brazilian study was funded by grant 2012-0417-0 from the São Paulo Research Foundation. Dr Jongsma is funded by the Economic and Social Research Council (grant ES/S011714/1). Dr Kirkbride is funded by the Wellcome Trust and Royal Society (Grant 101272/Z/13/Z). Dr Jongsma and Professor Jones are funded by the National Institute of Health Research Collaboration of Leadership in Applied Health Research and Care East of England. Professor Rutten is funded…
Early Parental Death and Risk of Psychosis in Offspring: A Six-Country Case-Control Study
Evidence for early parental death as a risk factor for psychosis in offspring is inconclusive. We analyzed data from a six-country, case-control study to examine the associations of early parental death, type of death (maternal, paternal, both), and child’s age at death with psychosis, both overall and by ethnic group. In fully adjusted multivariable mixed-effects logistic regression models, experiencing early parental death was associated with 1.54-fold greater odds of psychosis (95% confidence interval (CI): 1.23, 1.92). Experiencing maternal death had 2.27-fold greater odds (95% CI: 1.18, 4.37), paternal death had 1.14-fold greater odds (95% CI: 0.79, 1.64), and both deaths had 4.4…
The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings from the Multinational EU-GEI Study
The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) inte…
The incidence of psychotic disorders among migrants and minority ethnic groups in Europe: findings from the multinational EU-GEI study
AbstractBackgroundIn Europe, the incidence of psychotic disorder is high in certain migrant and minority ethnic groups (hence: ‘minorities’). However, it is unknown how the incidence pattern for these groups varies within this continent. Our objective was to compare, across sites in France, Italy, Spain, the UK and the Netherlands, the incidence rates for minorities and the incidence rate ratios (IRRs, minorities v. the local reference population).MethodsThe European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study was conducted between 2010 and 2015. We analyzed data on incident cases of non-organic psychosis (International Classification of …
The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study.
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 canna…
Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations
European Community Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. in this article, we aim to review these recent developments and illustrate h…
A MULTI-LEVEL FUNCTIONAL STUDY OF A SNAP25 AT-RISK VARIANT FOR BIPOLAR DISORDER AND SCHIZOPHRENIA
Background The synaptosomal associated protein SNAP25 is crucial for synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions. We recently identified a promoter variant in SNAP25, rs6039769, associated with bipolar disorder and gene expression in prefrontal cortex. Methods Here, we performed a genetic association study using this variation on two independent cohorts of 288 and 173 subjects with schizophrenia and 315 unaffected control individuals. We replicated our results using data from the schizophrenia group of the Psychiatric Genomics Consortium (PGC). Functional consequences combined both in vitro and post-mortem gene expression analysis on 30 p…
The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study
The work was supported by Guarantors of Brain post-doctoral clinical fellowship to DQ; Clinician Scientist Medical Research Council fellowship (project reference MR/M008436/1) to MDF; Heisenberg professorship from the German Research Founda- tion (grant no. 389624707) to UR; the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The EU-GEI Project is funded by the European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-…