EU-GEI Newsletter 3 (February 2014)
   
   

INTRODUCTION by Bart Rutten and Jim van Os
   
   

OUR RESEARCH: Assessing stress sensitivity in daily life - experience sampling research in EU-GEI
   
   

OUR RESEARCH: Looking at genetics from an environmental perspective
   
   

PUBLICATIONS: Life Events and Psychosis: a Review and Meta-analysis
   
   

EU-GEI PARTNER IN THE SPOTLIGHT: Omega Pro
   
   

A DAY IN THE LIFE OF: SERMAS, the Madrid research team
   
   

EU-GEI PARTNERS and affiliated partners
   
   

EU-GEI CONTACT
   


 



 
INTRODUCTION by Bart Rutten and Jim van Os


Dear readers,

Welcome to the third EU-GEI annual Newsletter.

The EU-GEI project has now reached its successful completion of the third project year. Within these first 3 years, the EU-GEI consortium has established a high-quality and well-running research infrastructure for our multicenter, multinational investigations on gene-environment interactions in schizophrenia. Data collection in EU-GEI is approaching the final stages, and we are now in the phase of planning the optimal analysis strategies for the large amounts of valuable data on genetic, environmental and clinical variables in patients, family members and control subjects that are collected within EU-GEI, while EU-GEI scientists are continuing to publish high-impact findings from early EU-GEI output.

One of the main challenges in mental health research is to obtain data of experiences and social context of people in the flow of everyday life. Our EU-GEI scientists have developed the Experience Sampling Method (ESM), a structured, random time-sampling diary technique. This detailed method is currently being used in Amsterdam, London, and Melbourne to assess these aspects and can be used to investigate important phenotypes such as sensitivity to stressors in the daily life of individuals with an at-risk mental state for psychosis.  This ongoing work is described in the news letter by Uli Reininghaus, one of the key scientists on this topic.

Other EU-GEI scientists have been very active in investigating the impact of life events on psychosis. Stephanie Beards and others performed a meta-analysis of relevant scientific studies on this topic, and their work by is highlighted in this newsletter as well.

While genotyping of the DNA of EU-GEI subjects is currently ongoing in the laboratories of Cardiff University, EU-GEI scientists are already performing large genetic discovery studies and are developing new techniques to summarise the signals of large gene-datasets of an individual into one score, thereby facilitating these endeavours.

Given that people with psychotic disorders differ in their biopsychosocial trajectories and neurobiological underpinnings for developing psychosis, EU-GEI scientists are currently exploring possibilities for findings biological pathways that are influenced by environmental exposures during life, and investigating whether subjects that carry genetic variants in these pathways may have higher risk for developing psychotic disorder, particularly when they encounter certain adversities during life. 

One of the key people in these genetic studies in EU-GEI is Alex Richards and he describes his recent work in the newsletter.

We hope you will enjoy reading this third annual Newsletter, and please feel free to contact us if you want to make a contribution in the future; input from all kinds of stakeholders and audiences is much appreciated!

Jim van Os and Bart Rutten
coordinators of EU-GEI



 

 





 
OUR RESEARCH: Assessing stress sensitivity in daily life - experience sampling research in EU-GEI

 

by Uli Reininghaus, Eva Velthorst, and Barnaby Nelson on behalf of the EU-GEI ESM group

Department of Psychiatry and Psychology - Maastricht University

Institute of Psychiatry - King’s College London

Department of Psychiatry – University of Amsterdam

Orygen Youth Health Research Centre - University of Melbourne

 

Understanding how genes and adverse social environments combine with each other and impact on individuals in the development of psychotic experiences (such as odd beliefs or unusual perceptual experiences) to increase risk of disorder is no doubt complex. One possibility that has been suggested is that individuals, who have a greater genetic risk for psychosis and who encountered problematic social environments in their life, particularly in childhood, may experience stronger emotional reactions in response to minor daily hassles or, in short, may be more sensitive to stress.  For individuals with such elevated stress sensitivity, psychotic experiences may, in turn, be more likely to persist and, ultimately, result in a transition to psychotic disorder.


In the GxE Prodrome Work Package of EU-GEI, the Experience Sampling Method (ESM), a structured, random time-sampling diary technique, is currently being used in Amsterdam, London, and Melbourne to assess stress sensitivity in the daily life of individuals with an at-risk mental state for psychosis. Participants are given a PsyMate®, an electronic device developed in Maastricht for sampling experiences in the context of daily life. For a period of 6 consecutive days, this gadget beeps 10 times per day and each time it beeps participants have to answer questions about minor disturbances and distinctive unpleasant events, emotional reactivity, and psychotic experiences.


Coupled with data on genetic risk and childhood adversity collected as part of the GxE Prodrome Work Package, this will allow to investigate whether stress sensitivity is an important psychological mechanism underlying the interplay of genes and early adverse environments in the development of psychosis. Statistical analysis will test whether individuals with greater genetic risk (i.e. higher polygenic scores) and prior exposure to childhood adversity experience stronger emotional reactions in response to minor daily hassles. These analyses will be probed further to investigate whether, in individuals with elevated stress sensitivity, psychotic experiences are more intense, more likely to persist and result in a transition to psychotic disorder.

Owing to the immense effort the team in Amsterdam, London, and Melbourne have put into collecting this data, so far, experience sampling assessment has been completed for a total of 82 participants. Recruitment is still ongoing and, once successfully completed, this will be the largest experience sampling study conducted to date in individuals with an at-risk mental state for psychosis. Evidence on stress sensitivity as a mechanism underlying the interplay of genetic and environmental factors will further our understanding of the aetiology of, and contribute to developing novel interventions for, schizophrenia and other psychoses.

 

Photo top: Uli Reininghaus (United Kingdom)
Photo middle: Eva Velthorst (the Netherlands)
Photo bottom: Barnaby Nelson (Australia)

 



 

 

 
OUR RESEARCH: Looking at genetics from an environmental perspective

 

Dr Alex Richards, bioinformatician at the Department of Psychological Medicine and Neurology, Cardiff University, WP3

Large Genome-Wide Association Studies have begun to open the door to a greater understanding of schizophrenia. However, it is not an easy matter to extract inferences about the aetiology and variety of symptoms from the mass of GWAS data. In our research, we aim to use the simple technique of polygenic scoring on the EU-GEI datasets to discover more about the disorder.

Polygenic scores are essentially a count of the number of risk alleles for a condition present across an individual's genome. These alleles are weighted by the log odds ratio for that SNP and thresholded by the significance of their association with the disorder of interest. These statistics, and the identity of the risk alleles, are calculated in an independent GWAS dataset. Genome-wide polygenic scores are predictive of schizophrenia status with a high level of significance in logistic regression.

We are constructing pathway-specific polygenic scores, restricted to SNPs found in genes in particular biological pathways. These gene sets come from a variety of sources, such as public databases such as the Gene Ontology, manual curation of the literature or large-scale transcriptomic and proteomic experiments. The gene sets are chosen on the basis of support from other datasets for a link with schizophrenia. Currently we are making polygenic scores for specific biological pathways, some of which are related to environmental sensitivity

To examine the interaction between genetics and the environment, we plan to look at the relationship between these pathway polygenic scores and specific environmental variables for particular hypotheses.

We hope to have the first results this coming year!



 

 

 
PUBLICATIONS: Life Events and Psychosis: a Review and Meta-analysis


Published in:        
Schizophrenia Bulletin 
(doi: 10.1093/schbul/sbt065)

EU-GEI author:   
Stephanie Beards 
P2 - Institute of Psychiatry, King's College London

Despite a surge of interest into the relationship between childhood adversity and psychoses, the impact of adverse experiences close to onset has received far less attention. In order to improve our understanding and consider avenues for future research, Beards and colleagues performed a systematic review and meta-analysis which looked closely into the association between recent stressful life events and the onset of psychosis. Studies were eligible if they assessed life events in adulthood (aged above 16 years) and included individuals had a first episode of psychosis or reported subclinical psychotic experiences. An electronic search of key scientific databases found 16 studies (published between 1968 and 2012), with 14 studies showing recent life events were associated with an increased risk of psychotic experiences and disorder. The effects were evident for up to 3 years prior to first occurrence of experiences, and clinical studies reported that recent exposure to life events were associated with a two to eight-fold increase in the risk of psychosis. Within the general population studies, the experience of recent stressful events appeared to increase the risk of psychotic experiences by two to seven times. A meta-analysis of a subgroup 13 studies that reported the number exposed and not exposed to life events found exposure to recent life events to be associated with a three-fold increase in risk among individuals with psychotic disorders or experiences. Many of the included studies were found to be limited by small sample sizes and the use of checklist measures of life events, with no consideration of the meaning and interpretation of events. Beards and colleagues concluded that life events may play some role in the onset of psychosis. The methodological quality of included studies, however, was weak and this makes it difficult to infer events cause psychosis.  Consequently, more methodologically robust research is needed to clarify the nature of this association.

Click here for the FULL ARTICLE as pdf



 

 





 
EU-GEI PARTNER IN THE SPOTLIGHT: Omega Pro


OMEGA PRO; established in March, 2008 and specialized at the area of clinical research, is one of five SME's participating in the EU-GEI
project.

Omega Pro is one of the sister companies of Omega CRO that was established in 1997 as a first contract research organization in Turkey. Omega Pro has 25 staff and provides high quality clinical and epidemiological research management to national and international consortia and other health-related organizations. Major services provided by Omega PRO includes project writing, project submission, project management, education, data management, statistical analysis, developing software, drug depot and management.

Omega PRO is an independent research organization specialized in Phase III and IV clinical trials and post marketing surveys encompassing the full range of services needed for large-scale studies. The senior staff has extensive experience in planning, conducting and monitoring clinical and epidemiological studies as well as in data management, data analysis, presentation of data and bioinformatics. In addition, Omega PRO offers training programs for pharmaceutical companies and investigators, and publishes educational materials, such as periodicals and serials. Omega PRO has been involved in various major, multi-centre trials in Turkey.

In the scope of EU-GEI project, Omega PRO works as a part of WP6 (GxE Vulnerability &Severity). Omega PRO provides database management of all samples collected in Turkey. Omega PRO also gives support to Ankara University (WP6 leader) in terms of EU-GEI research assistant management, consumable supply, logistic solutions, communication with project team and conducting field study.

You can visit the website at http://www.omega-pro.com.tr.



 

 

 
A DAY IN THE LIFE OF: SERMAS, the Madrid research team

6:30: Riiing! A typical working day starts for the EU-GEI team in Madrid! After a quick breakfast I run to the bus stop. It arrives late… again! It is 2ºC and it is raining…where has the Spanish sun hidden out today?
 

7:57: The research team meeting starts at 8 AM sharp and Celso is already waiting impatiently. I arrive huffing and puffing, but fortunately it seems that today I’m on time… Time to review all our projects:  “PEPs”, “PERS”, “PIT”, “SG-PIT”, “SG-BIP”, “2EPs”, “OPTiMiSE”, “EUGEI”…too many acronyms for a single cup of coffee! Recruitment has gone well this week. However, Celso is smiling in a way all people in our team know how to read:  NOT ENOUGH!

8:30: No time to waste, I run to the inpatient unit “searching for the EU-GEI man”, while Gonzalo starts to look for controls to recruit.  We knock all doors: “knock, knock, our recruitment is in trouble; who can help us?

10:00: Completely lost in the world of patients, siblings, controls, White noises and Degraded faces the morning goes by. I am so hungry!

14:30: Lunch time at last! (Yes, 2:30 PM, this is Spain…) As usual, we keep on speaking all at the same time and fighting to be first at the microwave queue “What do you have today for lunch? Have you cooked it yourself?” After this short break and one more cup of coffee, everything seems much easier…

15:30: Gonzalo leaves for the Community Mental Health Centers to review hundreds of clinical files!!

16:00: To round the day off, we go for a tour around Spain: it is time for a teleconference with the rest of the Spanish groups: “María, has the sun not appeared in Santiago yet?” “Sabrina, how was the weekend on the beach?” “Eva and Estela, how is everything going in Oviedo and Cuenca?”, “Bibiana and Silvia, any new cases in Barcelona?” Good luck with your recruitment and see you in two weeks!

17:00: The only thing left to do is reply to all the emails accumulated during the day, write the teleconference minutes and send them around.

But… wait! EU-GEI data are calling!! I hope you are not tired yet, because it is time now to think and write our EU-GEI hypothesis!

Oops! Where’s everybody gone? Time has gone by and it is still raining…Bravo! It is already 7:30 PM… I think today I will not go to the gym either….


Photo: Gonzalo López and Laura Roldán Diaz from the Madrid team



 

 

 
EU-GEI PARTNERS and affiliated partners


PROJECT COORDINATOR
Universiteit Maastricht

EU-GEI PARTNERS
Institute of Psychiatry / King's College London
Cardiff University
Central Institute of Mental Health
Ankara University
Servicio Madrileno de Salud
Academisch Medisch Centrum - Universiteit van Amsterdam
Institut National de la Santé et de la Recherche Medicale (INSERM)
Katholieke Universiteit Leuven
University Mental Health Research Institute
Medizinische Universität Wien
Universität Basel
Universität Köln - Universitätsklinikum
SERMES Planificacion
Wingz b.v.
E.C.S. International BV
Omega Pro Proje Arastirma Gelistirme ve Danismalik Ltd Pti
Mediamens B.V.
The University of Hong Kong
Universidad del Pais Vasco
The Chancellor, Masters and Scholars of the University of Cambridge
Royal College of Surgeons in Ireland
Ludwig-Maximilians-Universität München
Alma Mater Studiorium - Universita di Bologna
Universita Degli Studi di Palermo
University of Melbourne

For contact details see HERE

Affiliated partners
EU-GEI's affiliated partners are external parties participating in the project. As conditions of participation, affiliated partners have agreed to meet the EU-GEI standards with respect to the identification, recruitment and assessment of subjects. All related costs will be met by the new affiliated centers (with no funding being available form EU-GEI).

Universidade de Sao Paulo (Brazil)
University of Verona (Italy)
University of Copenhagen (Denmark)
UPC Kortenberg / Katholieke Universiteit Leuven (Belgium)
Centre Hospitalier Saine Anne - Paris (France)
Universitat Autònoma de Barcelona (Spain)
Federal University of Sao Paulo (Brazil)
University of Belgrad (Serbia)



 

 

 
EU-GEI CONTACT


EU-GEI contacts:

Project Management:
Karin Quanten
Maastricht University Medical Centre
Department of Psychiatry and Neuropsychology
Location Vijverdal
Vijverdalseweg 1, 6226 NB, Maastricht - The Netherlands
PO Box 616, 6200 MD, Maastricht - The Netherlands
T +31 43 3883600 / F +31 43 3884122
Karin.Quanten@maastrichtuniversity.nl

Wendy Beuken
Maastricht University Medical Centre
Department of Psychiatry and Neuropsychology
Location Vijverdal
Vijverdalseweg 1, 6226 NB, Maastricht - The Netherlands
PO Box 616, 6200 MD, Maastricht - The Netherlands
T +31 43 3883702 / F +31 43 3884122
W.Beuken@maastrichtuniversity.nl

This newsletter was produced as part of EU-GEI dissemination activities.
Contact: Karin Quanten

Design by MediaMens

EU-GEI: European Network of National Schizophrenia Networks studying Gene-Environment interactions
www.eu-gei.eu



 

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