Welcome to the second PRONIA newsletter. This time the group from the University of Udine is in charge to update you on the recent developments of the PRONIA project.  If you are new on our website and curious to know what the project is about, you can find an introduction to PRONIA in the first part of this newsletter.
In the following parts we will inform you on the project achievements and plans for the future. We will also report on recent meetings and give announcements of upcoming events.
Finally, let’s meet the team. This time we are presenting you the Italian PRONIA sites: The University of Udine, Ospedale Niguarda (Milan) and their PRONIA team members.

The PRONIA project is a European Commission funded study with collaborators in the UK, Germany, Italy, Switzerland, Finland and Australia. The purpose of PRONIA is to develop a computerised tool which can predict the onset and course of early psychotic illness. Reliable and broadly accessible prognostic tools will significantly alleviate the burden of psychotic illness by enabling individualised risk prediction, and paving the way to the targeted prevention of psychoses. However, to date no reliable prediction tools have been developed.

Primarily we are interested in the prediction of frank psychotic illness in individuals who are currently considered to be at risk of developing psychosis. Using a combination of different data types we hope to identify markers of risk which will allow us to predict whether an individual will develop psychosis, as well as which stage of psychotic illness they are currently in, and what their psychosocial outcomes will be.

To achieve this goal, we are collecting information on psychopathology, structural and functional neuroimaging, neuropsychological, metabolic and genomic data, as well as information on other factors that could affect outcome, such personality, trauma, resilience and coping strategies. We collect this information from four different groups of people aged 16-40 years: those with recent onset psychosis, young people who are at-risk for psychosis, individuals with recent-onset depression, and healthy controls who have never experienced living with a mental illness. We then follow up participants at multiple time points over an 18 month period in order to monitor the development or remission of their symptoms. Finally, the data collected undergoes complex machine learning algorithms in order to develop reliable prediction tools.

The PRONIA consortium is comprised of 7 academic partners; University of Birmingham, UK, Ludwig Maximilian University Munich, Germany, University Hospital Basel, Switzerland, University Hospital Cologne, Germany, University of Turku, Finland, University of Udine, Italy, and Melbourne Neuropsychiatry Centre, Australia; and 4 private sector partners; Dynamic Evolution, GE healthcare, GE Global Research, and GABO:mi.

Happy 2nd birthday to PRONIA! We are looking back on a successful and eventful 2nd year of PRONIA.  
During this time, all groups were very active in the recruitment of participants for PRONIA. Across all our recruitment sites the PRONIA participants’ population now counts 752 recruited subjects. Of these subjects 613 are still in the study (after excluding drop-outs and non-participations), including 132  individuals who are considered to be at risk of developing psychosis, 127 patients with a recent onset of psychosis, 121 patients with a recent onset of depression, and 233 healthy control participants. The clinical follow-up assessment at 9 months after recruitment has also started in all centers.
Besides the recruitment, the groups in the consortium were involved in various tasks to ensure the successful progression of PRONIA. Our colleagues from the University of Cologne organized monthly web based case conferences, with the help of Professor Frauke Schultze-Lutter, to discuss the clinical assessment of participants at high risk to develop psychosis. Also, they held web based trainings on the administration of clinical interviews and regularly monitored the quality of the data collected.
The group from the University of Udine worked hard to continuously improve the PRONIA PEBL battery of neurocognitive tests, which is administered via tablet, and developed a new battery for the assessment at 9 months’ follow-up. A series of web based trainings on the neurocognitive tests application also started in September 2015, along with the release of a manual and a video tutorial aimed at supporting the raters’ job and the training of new raters.
Two of our colleagues from the Ludwig-Maximilian-University (LMU) Munich and from the University of Basel travelled around Europe visiting the PRONIA recruitment sites to have scans of their brains acquired with each site’s MRI scanner. This was a big effort in terms of both financial and personal resources, but it was absolutely necessary for calibrating the MRI machines of the entire consortium.
WP1 (Data acquisition, clinical endpoints & predictors) and WP4 (Neurocognitive predictors) trainings, conferences/seminars, as well as MRI calibrations were done to ensure that all the relevant measurements are acquired in the right and same way, so that the results are reliable and comparable, across all PRONIA recruitment sites.
The colleagues from the LMU Munich, the University of Cologne and Dynamic Evolution in Germany further developed and improved the PRONIA portal, in order to give us an easy and safe tool to store the data collected across the consortium.

The 1st PRONIA Summer School took place in Munich from the 23 to the 26 of June 2015. This was a fantastic opportunity to have a first experience of working with the Neurominer algorithm. The School was a great success and, despite the very diverse background and experience level of the participants, thanks to an amazing group of very patient tutors, everyone could take home a good body of knowledge that will be highly valuable for the future analyses of the data collected by PRONIA.
Thanks to the Project Coordinator and his team for all their organizational efforts and for the warm hospitality at LMU Munich.

The first PRONIA scientific retreat took place in Basel on December 3 and 4, 2015. There, the members of the consortium discussed about the projects preliminary results and prepared a plan for the future scientific publications concerning the data collected so far.

The 4th Steering Committee Meeting took place in Munich at the end of April 2015. During the Meeting the PRONIA PIs discussed the results achieved so far, as well as the future goals.
The 3rd General Assembly Meeting was held as part of the 1st PRONIA Summerschool, where initial findings of the Summerschool were presented to the audience and future directions discussed.
PRONIA researchers held the 1st PRONIA Symposium at the 5th European Conference on Schizophrenia Research (ECSR) in Berlin from 24 – 26 September. The 90 min symposium "Predicting Psychosis – Methodological concepts and first findings of the 'Personalised Prognostic Tools for Early Psychosis Management' (PRONIA) project" was chaired by the PRONIA Coordinator PD Dr. Nikolaos Koutsouleris (LMU Munich) and Co-Chair Prof. Raimo Salokangas from partner University of Turku. Prof. Stephan Ruhrmann from the University of Cologne talked about “Multivariate clinical prediction of psychosis and its early course”, Prof. Stephen Wood from the University of Birmingham gave a talk titled “Predicting outcomes other than psychosis: past experiences and future approaches”, Dr. Claudia Lenz spoke of “Studying cross-center MRI scanner variations: initial experience from the PRONIA calibration study” and Carolina Bonivento, PhD, talked about “Automatic prediction of psychosis using cognitive measures: the PRONIA approach”.

The PRONIA teams are working with a high level of commitment towards PRONIA in order to achieve the project goals, as well as to constantly improve the tools and applications used in the consortium for data collection and analyses.
In the next months we will be able to do more explorative analyses of the data acquired so far, aiming to decide which factors are more likely to indicate a risk to develop a mental illness.

The group from the University of Basel will generate neuroimaging-based reference models which will be used to calibrate the PRONIA MRI data.
Across all sites we are enlarging the dataset of healthy control participants that are needed for setting the neurocognitive and MRI standards. We expect to be able to develop those norms next year.
Concerning the software, the University of Cologne, the LMU Munich and Dynamic Evolution will finalize the PRONIA@home that allows the participants to complete questionnaire measures at home. The Udine team is designing, and will implement PEBL - 2, which is aimed towards the future commercial use of our neurocognitive assessment tool. Our colleagues at LMU Munich are close to finalizing the machine learning platform NeuroMiner2, the core of the project that will allow building machine learning predictors based on the PRONIA data in a highly standardised way.
All the PRONIA sites are in the process of receiving ethical approvals to integrate the project ‘Harmonization of At Risk Multisite Observational Networks for Youth (HARMONY)’ into PRONIA. This will enable the cooperation between PRONIA and 3 other  studies investigating the prodromal signs of mental illnesses.
A second PRONIA Summer School is going to take place in June 2016 and a PRONIA Symposium will be organized in the framework of one of the major international Psychiatry conferences in 2016.

PRONIA’s consortium consists of 11 partners, and combined, makes up to over 100 individuals. Within this group, we come from a great range of backgrounds, including: clinical psychology; neurology; radiology; bio-engineering and psychiatry. Along-side our work on PRONIA, consortium members are working on other prestigious research projects, and presenting at conferences both nationally and internationally. Listed below are a few of our consortium members’ most recent achievements.

Marco Garzitto, PhD. Psychologist. He works at the development and maintenance of the PRONIA cognitive battery and at the participants’ recruitment and assessment in the Udine site.

Giuseppe Cabras, PhD. Computer scientist. He works at the development and maintenance of the PRONIA cognitive battery.

Marta Re, PhD. Engineer. She works at the development and maintenance of the PRONIA cognitive battery and at the MRI scans acquisitions.

Marika Belleri. Psychologist. She works at the participants’ recruitment and assessment in Milan.

Jessica Pellizzari. MD. Resident. She helps us in the recruitment and assessment of patients with recent onset psychosis.

A special thanks to all the residents of the Clinic of Udine for helping us with the recruitment!

Director of the Psychiatric Clinic of the Università di Udine Prof. Matteo Balestrieri

Sara Piccin, PhD (Research Fellow) After graduating in Psychology at the Università degli Studi di Trieste, she obtained her PhD at the Università di Udine with a thesis exploring the effectiveness of a video modeling protocol in rehabilitation of children with autism. She worked with Prof. Paolo Brambilla at projects exploring the risk of mental illness in children and adolescents. She is involved in the participants’ recruitment and assessment at the Udine site. Beside her research activities, she is specializing in psychotherapy.

Adele Ferro, PhD (Research Fellow) She graduated in Psychology at the University of Parma, she obtained her PhD at the University of Verona with a thesis with title “A structural magnetic resonance imaging study of the parietal lobe in bipolar disorder”. In her thesis she investigated the possible volumetric differences in the parietal lobes in patients with bipolar disorder with respect to controls. She worked with Prof. Paolo Brambilla carrying on her PhD topic, also in cooperation with the University of Santander (Spain). She is responsible for recruitment and testing in Milan.

Carolina Bonivento, PhD (Research Fellow) After graduating in Psychology at the Università degli Studi di Trieste, she obtained her PhD at the University of Birmingham (UK) under the supervision of Prof. Glyn Humphreys, with a thesis on ideomotor apraxia. In her thesis she run VBM analyses on CT and MRI scans that related the patients’ imitative skills to lesion of brain areas. Back in Italy she started working with Prof. Paolo Brambilla at projects investigating the risk of mental illness in children and adolescents. She is been in PRONIA since 2014 and she is the referent for the neurocognitive evaluations for the whole PRONIA consortium.

Prof. Paolo Brambilla (Principal Investigator) Paolo Brambilla, PhD MD, is Associate Prof. of Psychiatry, University of Milan, Italy, and Adjunct Associate Prof. of Psychiatry, University of Texas at Houston, USA. He is leading cognitive MR studies in adult and child psychiatry. His current lifetime h-index is 47 and he is author of more than 170 original papers. He is member of the “Imago 7” Foundation, which is dedicated to research using UHF 7T-MRI (www.imago7.eu). As of April 2015 he is Editor in Chief of the Journal of Affective Disorders.

The Unit of Brain Imaging and Neuropsychology @ Università di Udine and Programma 2000 @Hospital Niguarda (MI)

The Unit of Brain Imaging and Neuropsychology (RUBIN - http://icbn.uniud.it) was established in 2003 at the Università di Udine (www.uniud.it). Our main interest have always been the investigation of the neurobiological features of the major psychoses (bipolar disorder, schizophrenia, and unipolar depression), their relation with neuropsychological and genetic domains, as well as their possible causal role in the onset of a mental illness.
Since the foundation of RUBIN, we have developed a substantial expertise in neurocognitive assessment of mentally ill patients, as well as in Magnetic Resonance Imaging (MRI) techniques:  structural MRI (sMRI); diffusion tensor imaging (DTI), tractography, perfusion weighted imaging (PWI), MR spectroscopy (MRS), and functional MRI (fMRI).

RUBIN closely cooperates with the University of Verona, and together they form the InterUniversity Center for Behavioral Neurosciences (ICBN) since 2005. We also work in partnership with the Neuroimmunology Unit of Ospedale San Raffaele in Milan, at the characterization of patients’ immunological blood profiles.

Since Prof. Paolo Brambilla was appointed as Associate Professor of Psychiatry at Università di Milano (info at www.unimi.it), RUBIN started a strict cooperation with that site.

Programma 2000 at the hospital Niguarda of  Milan (info at www.programma2000.org) is also giving a substantial contribution in enlarging the sample of PRONIA participants from the Italian sites.

GABO:mi

Since its release online on 26.02.2014, the PRONIA website (www.pronia.eu) counts 20.733 sessions in 136 countries; in 60 of those countries all over the world we have even had more than ten sessions per country on the PRONIA website. We update our website on a regular basis and look forward to attracting more visitors to our pages, which offer information for scientists and professionals as well as help-seekers and relatives. The section for investors is now online, including PRONIA information for investors, a section on the PRONIA patent application and an FAQ section.
Thanks to the team at GABO:mi, together with the other PRONIA partners, for implementing the website and for its continuous maintenance.

University of Turku

MD Otto Turtonen started in PRONIA in March. He has graduated from the Medical Faculty of University of Turku in 2013. He is working part-time in PRONIA and is specializing in psychiatry on the psychiatric hospital ward of Turku welfare division.
M.Sc. Janina Paju joined our team in October 2015. Janina is a psychologist and has graduated from Åbo Akademi University in 2013. She works part-time in PRONIA and part-time in the Clinical Research Services of Turku CRST. 
Prof. Salokangas had two new publications:
Salokangas RKR. Käypä hoito ei unohda skitsofreniapotilaiden tarpeita. (In English: The Schizophrenia Guidelines do not forget the need of schizophrenia patients) SLL 2014;69:31-42.
Salokangas RKR. Psykoosien varhainen tunnistaminen viivästyy. (In English: Early detection of psychoses is still delaying.) Duodecim 2015;131:815-6.

University of Birmingham

Katharine Chisholm and Stephen Wood along with other colleagues published a paper in Neuroscience and Biobehavioral Reviews: The association between autism and schizophrenia spectrum disorders: A review of eight alternate models of co-occurrence. (2015) Katharine Chisholm, Ashleigh Lin, Ahmad Abu-Akel, Stephen J. Wood, Neuroscience and Biobehavioral Reviews 55 173–183
New Study members:
Alexandra Stainton started her PhD with us in September. Alex has completed her MSci in Psychology at the University of Birmingham, graduating with a first honours degree. Her MSci placement was on the PRONIA project, and during this time she proved herself to be a vital team member. Alex is focusing on neurocognition and resilience for her PhD.  
We are also currently advertising for a second PhD student who will work specifically on work package 6. This second PhD student will focus on multimodal data and machine learning techniques with the pronia data. The PhD candidate’s primary role will be to systematically investigate whether the different combinations of data channels collected by PRONIA improve accuracy and reliability of prediction in individuals with emerging mental health difficulties. The predictive power of the different types of data collected by PRONIA (clinical, neurocognitive, MRI and genetic data) will be optimized by pooling them together. Using this pooled ‘multi-modal’ data, the PhD candidate will create models which will predict prognostic outcomes significantly better than current models which employ only one type of data. The PhD role will be based at the University of Birmingham but will involve a placement in Munich, Germany. The advert for this position closed at the end of November and the first interviews were conducted in December.

University of Cologne

As member of the board of the Section on Prediction of Mental Disorders of the European Psychiatric Association (EPA) and of the respective writing groups, Prof. Stephan Ruhrmann co-authored two new guidance publications, the EPA guidance on the early detection of clinical high risk states of psychoses and EPA guidance on the early intervention in clinical high risk states of psychoses (Schultze-Lutter et al., 2015; Schmidt et al., 2015). As member of the Section for Prevention of Mental Disorders of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), he co-authored a survey investigating the structure of the Early Recognition Centers in Germany: Services on early recognition of psychoses and bipolar disorders in Germany: inventory survey study (Leopold et al., 2015). His group published a Systematic review and meta-analysis on the predictive value of event-related potentials for the prediction of psychosis:  Forecasting psychosis by event-related potentials-systematic review and specific meta-analysis (Bodatsch et al., 2015). Together with Professor Frauke Schultze-Lutter and other colleagues, he published a paper on the meaning of personality dimensions in persons clinically at high-risk: Personality dimensions in persons symptomatically at risk of psychosis: pronounced but lacking a characteristic profile (Schultze-Lutter et al., 2015). Together with Professor Paolo Fusar-Poli and Professor Philip McGuire, he co-authored a meta-analysis on functioning in clinical high-risk samples: Disorder, not just state of risk: meta-analysis of functioning and quality of life in people at high risk of psychosis (Fusar-Poli et al., 2015). As a former co-investigator of the first episode related section of the German Research Network on Schizophrenia, he co-authored an analysis of relapse predictors: Predictors for symptom re-exacerbation after targeted stepwise drug discontinuation in first-episode schizophrenia: Results of the first-episode study within the German research network on schizophrenia (Gaebel et al.,2015). At the DGPPN Congress in Berlin, 25-28 November 2015, Marlene Rosen and Dr. Theresa Haidl presented a poster regarding level of expressed emotions and transition to psychosis. Further, Nathalie Kaiser presented a poster about the remission of patients at clinical high risk at the DGPPN Congress 2015.

LMU Munich

The PRONIA Team from Munich (Dr. Joseph Kambeitz, Dr. Lana Kambeitz-Ilankovic, Carlos Cabral and PD Dr. Nikolaos Koutsouleris) published a paper in Neuropsychopharmacology on MRI-based classification of schizophrenia. The paper indicates the importance of moderatoring variables like age, clinical symptoms or antipsychotic medication for the accuracy of MRI-based decision models. At the DGPPN conference in Berlin, PD Dr. Nikolaos Koutsouleris (Coordinator of the project) was invited to present in multiple sessions. In his talks he presented data from different studies covering the multiple areas of application of multivariate prediction models in psychiatry. Also at the DGPPN Dr. Lana Kambeitz-Ilankovic gave a talk on her recent results regarding the promise of MRI data fusion techniques in improving diagnostic accuracy of machine learning classifiers.
At the PRONIA Team in Munich we are happy to welcome two new members. Anne Erkens and Michaela Amft are both medical students that will assist the project in the recruitment process and write their doctoral thesis with us. Anne is mainly interested in resilience factors and clinical moderators of stress effects on psychosocial functioning in patients with depression and subjects with clinical risk for psychosis. Michaela will investigate brain structural alterations associated with perceived stress in subjects with recent onset psychosis.

University of Udine

This year Prof. Paolo Brambilla (Principal Investigator in Udine/Milan) was appointed Associate Professor of Psychiatry, University of Milan, Italy. On April 2015 he was also nominated Editor in Chief of the Journal of Affective Disorders.
Dr. Adele Ferro (research fellow) presented a poster at the 55th International Neuropsychiatric Congress in Pula (HR) in June 2015, with the title: “The Parietal Lobe in Bipolar Disorder: A Cross Sectional and Longitudinal Study Using Structural MRI”. The poster was judged the 3rd best poster at the conference and was awarded a price consisting in a travel grant for participating at the meeting next year.
Dr. Sara Piccin (research fellow) presented a poster at the 27th ECNP Congress in Berlin from 8-21 October 2014, with the title: "COMT Modulates Working Memory and Impulsivity Control in Bipolar Disorder”. The poster abstract was published in the journal of the European Neuropsychopharmacology (ENP).
Prof. Paolo Brambilla (PRONIA Principal Investigator), Dr. Carolina Bonivento, Dr. Marco Garzitto, Dr. Livia Fornasari (research fellows), contributed to the publication of the work: “Deficit di regolazione emotiva in età evolutiva: analisi dei profili di funzionamento in un campione clinico italiano.