EU-GEI

European Network of National Schizophrenia Networks Studying Gene-Environment Interactions

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 Obiettivo del progetto (Objective)

'The aim of EU-GEI is to identify the interactive genetic, clinical and environmental determinants involved in the development, severity and outcome of schizophrenia (EU-GEI, Schiz. Res. 2008; 102: 21-6). In order to identify these interactive determinants, EU-GEI will employ family-based, multidisciplinary research paradigms, which allow for the efficient assessment of gene-environment interactions. In order to go beyond old findings from historical convenience cohorts with crude measures of environmental factors and clinical outcomes, the focus in EU-GEI will be on recruitment of new, family-based clinical samples with state-of-the-art assessments of environmental, clinical and genetic determinants as well as their underlying neural and behavioural mechanisms. New statistical tools will be developed to combine the latest multilevel epidemiological with the latest genome-wide genetic approaches to analysis. Translation of results to clinical practice will be facilitated by additional experimental research and risk assessment bioinformatics approaches. This will result in the identification of modifiable biological and cognitive mechanisms underlying gene-environment interactions and the construction of Risk Assessment Charts and Momentary Assessment Technology tools which can be used for (i) early prediction of transition to psychotic disorder in help-seeking individuals with an at-risk mental state and (ii) early prediction of course and outcome after illness onset. In order to reach these goals, EU-GEI has assembled a multidisciplinary team of top schizophrenia researchers who have the range of skills required to deliver a program of research that meets all the call’s requirements and who have access to / will collect a number of unique European samples. The partners in EU-GEI represent the nationally funded schizophrenia / mental health networks of the UK, Netherlands, France, Spain, Turkey and Germany as well as other partners.'

Introduzione (Teaser)

Up to 3 % of people develop a psychotic disorder in the course of their lives, and approximately 1 % develop schizophrenia, one type of psychotic disorder. European researchers, together with international partners, are looking into measuring the genetic, clinical and environmental factors and mechanisms that determine the development, severity and outcome of schizophrenia.

Descrizione progetto (Article)

People with psychotic disorders are overwhelmed by inner experiences that disturb their ability to connect in an adequate way with their social environment. Importantly, there is currently no reliable method allowing prediction of the risk of an individual to develop a psychotic disorder.

The risk of developing a psychotic disorder is known to be related in particular to both a person's genetic make-up, and environmental factors during his/her course of life. These factors include adversity during childhood, belonging to a society's minority group, drug addiction, or just living in a city rather than in a rural environment. Twin studies show that susceptibility to developing a psychotic disorder may be to 50 % determined by genetics. It is assumed, but still needs to be rigorously tested, that a person's genetic make-up also influences the role that environmental factors can play to enhance/or decrease risk for psychiatric disorders to develop.

To address this key question, a multidisciplinary, multinational collaboration within, and beyond, Europe has been initiated, the EU-funded 'European network of national schizophrenia networks studying gene-environment interactions' project (http://www.eu-gei.eu (EU-GEI)).

EU-GEI is investigating genetic, environmental, behavioural and clinical variables in samples and data from more than 7 500 individuals, including families of patients with psychotic disorders, twin pairs and individuals from the general population.

In order to better understand fluctuations in behaviour and experiences in the flow of daily life, EU-GEI scientists have developed the PSYMATE device and application. This data collection and software tool, is able to capture multiple parameters during moments in the flow of people's everyday life, and is thus providing a 'film' rather than a 'snapshot' of the patient's day. Data from the PSYMATE tool helps to empower patients in managing their own lives, helps clinicians in terms of diagnosis and it can contribute to the evaluation of mental health care interventions.

The EU-GEI website is up and running, providing both information for the general public and patients as well as a web-based training package available for researchers in the centres that are participating in the clinical study under the project.

A fully functional database has been established that handles the large quantities of incoming data from the large EU-GEI cohorts that will provide the largest set of data available on genetic, environmental, behavioural and clinical variables in psychosis, in particular schizophrenia. DNA samples collected under the EU-GEI study are all genotyped in the project's centralised genotyping facilities, and a large number of subjects have already been genetically analysed.

Approaches for statistical analyses of the complex EU-GEI data sets have been developed and are currently in use. The full data set from the Dutch part of the study has become available and is currently under investigation for genotype x environment interactions. First explorations have already provided replicated evidence that the impact of cannabis use on psychosis is moderated in people that carry a specific variant of the AKT1 gene.

Considerable progress has been made in discovering genetic variants that increase risk for schizophrenia. Moreover, functional neuroimaging studies have discovered correlates of environmental exposures in the brain.

The prime clinical relevance of the EU-GEI project will be the establishment of risk assessment charts based on genetic, environmental, behavioural and clinical variables. These momentary assessment tools, which are amendable to predict risk to develop clinical manifestation of psychotic disorders, will significantly improve diagnosis, treatment outcome prediction and treatment evaluation.