MH&NS School for Mental Health and Neuroscience Annual Report 2012 ruimte voor illustratie/beeld van het A-merk in blauw Maastricht University Faculty of Health, Medicine and Life Sciences & Health Institutes: Academic Hospital Maastricht RIAGG Maastricht PMS Vijverdal Mondriaan Zorggroep Heerlen
Content Preface Professor Dr. Harry Steinbusch 3 1. Future directions of MH&NS and EURON 5 2. Organizational structure 8 3. Divisions 11 3.1 Division I: Cognitive Neuropsychiatry and Clinical Neuroscience 11 3.1.1 Division I: Research lines 12 3.2 Division II: Mental Health 15 3.2.1 Division II: Expert groups 16 3.3 Division III: Neuroscience 20 3.3.1 Division III: Research lines 20 4. Facts and Figures 29 4.1 Earning Power 29 4.2 Research Staff 32 5. Output results 36 5.1 Aggregated results of the School Output 2012 36 5.2 Best publications 2012 36 5.3 PhD theses 2012 38 6. Master and PhD Educational Activities 42 6.1 Master Programme 42 6.2 PhD Programme 42 Annexes: I MH&NS / EURON PhD Educational Programme 2012 45 II Current PhD theses 48 III Publications 57 MH&NS Annual Report 2012 2
Preface Prof.dr. Harry W.M. Steinbusch Scientific Director I am pleased to provide you with our Annual Report 2012. It presents an overview of the work and full information concerning the School for Mental Health and Neuroscience in the fields of research output, earning power, staff members and postdoctoral teaching activities in 2012. The School has grown further not only regarding the number of publications as requested by the Faculty of Health, Medicine and Life Sciences but also in the quality of the papers as indicated by an increase in the average impact factors. We are not to have more papers, but only more papers in the top 10% and 25% of the impact fields in which we are working. The increase in non-tenured staff members has resulted in a steady increase in the number of PhD theses to 32 in 2012. Our School now hosts about 170 PhD students. The guidance of these students is a significant challenge that requires an enormous and coordinated effort of all our staff members. In accordance with the performance contract with the Faculty of Health, Medicine and Life Sciences we have focused on establishing more funding from NWO (Dutch Medical Research Council) and FP7- EU grants, which has resulted in depending less on grants obtained from other peerreviewed agencies. Grants obtained from industrial contract research now represent a more limited component of our funding. However, it is worth noting that neuroscience research is still quite fragmented in the capital area. This speaks to the need for closer cooperation among the different units. Restructuring has resulted in one division focused on Cognitive Neuropsychiatry and Clinical Neuroscience, one division on Environmental Psychiatry and the third one on Fundamental and Systems Neuroscience. In line with this, educational activities of the Master s programs correspond to these three divisions. The strength of MH&NS is in its translational approach. For example, division 1 concerns neuroepidemiology and brain imaging, division 2 focuses on gene-environmental changes/interactions related to psychiatric disturbances such as psychoses, and division 3 uses animal and cellular models related to systems-level research. These lines of research at MH&NS will continue to find much synergy within collaborative projects and research networks, in the areas of Translational Neuropsychiatry, combined epigenetic studies and studies related to the disturbances of the Brain vasculature, leading to Vascular dementia and a dysfuctioning of the Blood Brain Barrier. The proportion of foreigners on staff has been steadily increasing to approximately 26% for researchers in 2012. In conclusion, I would like to thank all members of MH&NS for contributing their knowledge and expertise to the School and students in the past years. Importantly, these changes and improvements that have been made will create new opportunities for the upcoming years. I look forward to new directions and challenges in the restructured academic environment in the coming years. Prof.dr. Harry W.M. Steinbusch Scientific Director School for Mental Health and Neuroscience MH&NS Annual Report 2012 3
Chapter 1
Future directions of the School for Mental Health and Neuroscience (MH&NS) The mission of the School for Mental Health and Neuroscience at Maastricht University and the European Graduate School for Neuroscience, EURON, at the Euregional level, is threefold: 1. focusing on a basic understanding of brain function and disease mechanisms, 2. understanding the function of genes and proteins, cellular processes and neuronal networks in relation to human health, 3. establishing reciprocal translational links between lab and clinic and reverse. This mission can be made possible by building on multidisciplinary approaches. Therefore, as a foundation we will continue to educate and train Master and PhD students to become independent researchers who are able to plan and execute cutting edge science and to function well in multidisciplinary research programs in academia and/or industry. We use as slogan Through Excellence in Education and Research towards Innovation and Translation. This will be achieved by sharing expertise and knowledge among not only within our School of Mental Health and Neuroscience but also in conjunction with our EURON partners and by stimulating mobility of Master and PhD students. In addition, we aim for uniformity or comparability of standards for PhD degrees among the four participating countries, i.e., the Netherlands, Belgium, Germany and France which ultimately should lead to double or joint degrees. Indisputably, the training of young competent PhD s in Neuroscience is crucial to maintaining the competitiveness of the European community in Neuroscience-based research. The new generation of our neuroscientists should be capable of integrating information across different levels of research. Similarly, they should be competent to participate in integrative projects as a next step in elucidating the complex interplay between multiple genetic and environmental factors in order to reveal how this interplay translates into normal brain function and/or disease. Strategic Goals for MH&NS 2013 2016 The School will be facing in the immediate forthcoming period some important changes. However, we believe change will also create opportunities. The first opportunity is related to the establishment of the Maastricht University Medical Center (MUMC) and the fact that the MUMC has decided to stimulate and invest an amount of C0.5 million for the expansion of the research capacity of Contextual Neuroscience, the clinical counterpart of MH&NS within MUMC+. The School will try to match with an additional C0.5 million. The additional funding provided by MUMC will be deployed with a view to put in effect and consolidate strategic choices for expansion and strengthen the positions of postdocs and researchers at the assistant professorship level. At present, all these positions are, unfortunately, non-tenured while what is really needed are tenure-track positions to support and recruit excellent career-oriented staff members from within or beyond. Another consideration regarding Strategic Goals for the years till 2020 is the implementation of a so-called Profile Contextual Neuroscience, a Care Clinical Research Unit, headed by Prof.dr. J. van Os. This new Profile will start at the end of 2013 and will deal with all aspects of mental health related issues related to research, patient care and education in the Academic Hospital Maastricht. The Profile and the School will jointly work together. As mentioned before this relationship has resulted in direct opportunities for translational research from bed to bench and vice-versa. Finally, we would like to provide some additional thoughts with respect to EURON. We have mentioned before that MH&NS is a fully integrated partner in EURON and moreover the coordinator. However, EURON comprises nine other universities in the Euregio as well. MH&NS has been taking the lead in all organizational aspects. Because MH&NS Annual Report 2012 5
it already provides an excellent opportunity for networking, further Euregional activities and introducing an international or European Master in Translational Neuroscience have great potential, which we will incorporate in the next period. A further specific point deserving of attention is our partnership with the Faculty of Psychology and Neuroscience (FPN). In our School within Division 1, the Department of Psychopharmacology, (FPN) headed by Prof.dr. J. Ramaekers is already participating. In addition, there is a strong link with educational activities at the level of the Research Master Program Cognitive and Clinical Neuroscience in which the School is involved in 2 of the 4 tracks. Thus the FHML is the principal coordinator of two tracks of the Research Master. We would like to build further and even strengthen our partnership with other groups in FPN, such as the Neuroimaging group of Prof.dr. R. Goebels and the Neuroplasticity group of Prof.dr. P. De Weerd. These partnerships are important for research and educational exchanges and should result within the next period result into Neuroscience Institute Maastricht (NIM). The foundation of our future plans is that the research within MH&NS is divided into the three reorganized divisions. The choice for three divisions is based upon methodsrelated considerations: division 1 on patient care related cognitive neuropsychiatry and clinical neuroscience; division 2 on patient care-related gene environment investigations, and division 3 on animal models for neurodegenerative disorders. The research within MH&NS is based upon translational perspectives, in which the patient and related problems is the prime focus within the different clinical disciplines in particular Psychiatry and Neuropsychology and Neurology. The patient related studies or cohorts can be divided in patients with early life events problems (Division 2) or late-life event problems and aging (Division 1). Division 2 has an emphasis on gene-environment interactions in relation to neuropsychiatric and neurological disorders as studied in healthy and clinical human studies with as major clinical pictures schizophrenia and depression. The research of Division 1 is related to neuropsychiatric and neurological disturbances studied in healthy and clinical humans focused upon Alzheimer s disease and stroke. In the typical Maastricht University matrix structure towards both divisions, Division 3 is strategically positioned again from a translational perspective to perform animal experimental studies. The emphasis is upon cellular, molecular and behavioral processes underlying neurodegeneration and plasticity on animal models for Alzheimer s disease, Parkinson s disease, epilepsy, schizophrenia and pain. To summarize, MH&NS wants to move forward towards a Center of Excellence. We are aming together with the MUMC+ to formulate steps to increase our critical mass. We have already increased a variety of funding opportunities and we will continue to do so thereby increasing the number of Ph.D. students and postdocs. We intend to gain international recognition, showing this consistently on a translational level. In this way we clearly will distinguish ourselves within the national and international competition. To reiterate, the focus of MH&NS will be on three levels: 1. Research: three divisions working through a matrix model on joint translational neuroscientific clinical problems; 2. Education: expanding and strengthening Research Master, Ph.D. and postdoctoral activities; 3. Collaboration: further exploring the possibilities for a two faculty based Neuroscience Maastricht. MH&NS Annual Report 2012 6
Chapter 2
Organizational structure MH&NS is managed by the Board of MH&NS. The board is the body where strategis issues are discussed and effectuated. It consists of five members: the scientific director, the managing director and the three division leaders. Dean of the Faculty Health, Medicine and Life Sciences Prof.dr. Albert Scherpbier Managing Director Laurent Louwies Scientific Director Prof.dr. Harry Steinbusch Cognitive Neuropsychiatry and Clinical Neuroscience Prof.dr. Frans Verhey Deputies Dr. Martin van Boxtel Dr. Caroline van Heugten Psychiatry & Neuropsychology (section Neuropsychology) Movement Sciences General Practice Radiology Othorhinolaryngology Neurology Mental Health Prof.dr. Inez Myin-Germeys Deputy Dr. Koen Schruers Psychiatry & Neuropsychology (section Psychiatry) Neuroscience Prof.dr. Marc de Baets Deputies Prof.dr. Martin van Kleef Dr. Yasin Temel Psychiatry & Neuropsychology (section Neuroscience) Neurosurgery Anesthesiology Urology Ophthalmology Neurology Pediatrics Figure 2.1 Organogram of MH&NS: the contribution of the different Departments of FHML to the current three Divisions of MH&NS. Participating departments Core Departments Anesthesiology, Prof. Dr. W. Buhre Neurology, Prof. Dr. R. Van Oostenbrugge - Clinical Neurophysiology, Prof. Dr. W. Mess Neurosurgery, Prof. Dr. J. Van Overbeeke Ophthalmology, Prof. Dr. W. Webers Psychiatry & Neuropsychology, Prof. Dr. J. Van Os Urology, Dr. G. Van Koeveringe Non Core Departments General Practice, Prof. Dr. J. Metsemakers Human Movement Science, Prof. Dr. M. Hesselink Internal Medicine, Prof. Dr. C. Stehouwer General Practice, Prof. Dr. J. Metsemakers Pediatrics, Prof. Dr. L. Zimmerman Orthorhinolaryngology, Prof. Dr. B. Kremer Radiology, Prof. Dr. J. Wildberger MH&NS Annual Report 2012 8
Members of EURON MH&NS is the coordinator of the European Graduate School of Neuroscience (EURON). EURON is a research and training network of 11 universities in four countries i.e. Belgium, Germany, France and the Netherlands. EURON MH&NS Belgium Université Libre de Bruxelles Universiteit Hasselt Katholieke Universiteit Leuven Université de Liège Université catholique de Louvain Germany RWTH Aachen University University of Bonn University of Cologne Saarland University, Homburg France Université Lille 1 Figure 2.2 EURON in relation to MH&NS. The Netherlands Maastricht University (MH&NS) MH&NS Annual Report 2012 9
Chapter 3
Divisions Goals & Results 3.1 Division I: Cognitive Neuropsychiatry & Clinical Neuroscience Division Leader: Prof.dr. Frans Verhey Deputies: Dr. Martin van Boxtel Prof.dr. Caroline van Heugten Prof.dr. Robert van Oostenbrugge Dr. Paul Hofman Staff: Dr. Pauline Aalten Dr. Jos Adam Dr. Marjan van den Akker Prof.dr. Bert Aldenkamp Dr. Lucien Anteunis Dr. ir. Walter Backes Dr. Saartje Burgmans Prof.dr. Jan Willen Cohen Ter Vaart Dr. Jeanette Dijkstra Dr. Annelien Duits Dr. Carin Faber Dr. Ed Gronenschild Prof.dr. Fred Hendrikse Dr. Paul Hofman Prof.dr. Raymond Hupperts Dr. Jaap Jansen Dr. Heidi Jacobs Prof.dr. Herman Kingma Dr. Sebastian Köhler Dr. Vivian Kranen van Mastenbroek Prof.dr. Bernd Kremer Dr. Abraham Kroon Dr. Albert Leentjens Prof.dr. Peter de Leeuw Prof.dr. Werner Mess Prof.dr. Job Metsemakers Prof.dr. Felix Mottaghy Prof.dr. Rudolf Ponds Dr. Inez Ramakers Dr. Jennifer Reijnders Dr. Olga Schiepers Dr. Pieter-Jelle Visser Prof.dr. Hans Vles Dr. Marielle Vlooswijk Dr. Marjolein de Vugt Prof.dr. Joachim Wildberger Dr. Ieke Winkens Dr. Claire Wolfs Goals & Results CNP&CNS performs fundamental and applied research on brain-cognition relationships. CNP&CNS mission is to generate new insights into neurocognitive and neurobehavioural mechanisms which may help us to improve the treatment and care for people with cognitive and other neurological disorders. Since 2009, clinical neuroscience researchers have been assigned to the Division 1 Cognitive Neuropsychiatry & Clinical Neuroscience (CNP&CNS), a name expressing the translational nature of the research program. With respect to the medical core topics, the focus is upon neurodegeneration in relation to neurodegenerative diseases of the central nervous system, more specifically Alzheimer s disease and its prodromal phases, Parkinson s disease, peripheral nervous system disease, such as small fiber neuropathy, acquired brain damage, such as stroke, traumatic brain injuries, and epilepsy. Researchers in the division investigate the contribution of biological, neuropsychological and psychosocial factors, single and in combination, and the effect of ageing on the normal development of normal neurocognition and on mild to severe cognitive dysfunction. Research in Division 1 is typically conducted in a multidisciplinary way, with contributions of scholars with a background in neuropsychology, cognitive neuroscience, neuropsychiatry, clinical neurology, neuroradiology and neuroepidemiology. In 2012, we further pursued our studies into normal, successful and pathological ageing, with a great interest in translating basic insight into practical application. Studies that are carried out as part of the NWO/FES program on Brain and Cognition are producing the first results and products. New grants were obtained from both national and international (EU) sources. 14 PhD students successfully defended their thesis. Below, several examples are presented of ongoing and recently started research projects that are at the core of the research in this division. MH&NS Annual Report 2012 11
3.1.1 Division I Research lines Research-Line: Neurodegenerative disorders: mechanisms, early diagnosis and biomarkers P.I.: Prof.dr. F. Verhey, Dr. P-J Visser Post docs: Dr. P. Aalten, Prof.dr. R. van Oostenbrugge, Dr. P. Hofman, Dr.ir. W. Backes, Dr. J. Jansen, Dr. A. Leentjens, Dr. M. van Boxtel, Dr. S. Köhler, Dr. A. Duits, Dr. S. Burgmans, Dr. H. Jacobs PhD-students: Drs. S. Aarts, Drs. L. Clerx, Drs. B. Dandachi-Fitzgerald, Drs. R. Drijgers, Drs. L. Elias, Ir. H. van de Haar, Drs. H. Handels, Drs. M. Huijts, Drs. M. Legra, Drs. A. Moonen, Drs. S. Schievink, Drs. N. Vermunt, drs. T. Van der Voort, Drs. S. Vos Focus of research: Translational research into the early diagnosis of pathological ageing A large-scale national biobank, coordinated by MUMC and the VU-MC, formed the infrastructure for translational research into the early diagnosis of pathological ageing (Parelsnoer Neurodegeneratief), initiated by F. Verhey. Novel diagnostic technology for the early detection of Alzheimer s disease will be examined and evaluated in terms of Health Technology Assessment, i.e., with respect to its added value to existing diagnostic procedures (LeARN, CTMM). A project funded by VSB was started on the prediction of individual trajectories in cognitive disorders. Collaboration with the Departments of Neurology and Radiology was intensified, which has led to a new study on neurovascular mechanisms of cognitive disorders, and the interaction between vascular and neurodegenerative mechanisms. To assess brain microvascular pathology in the brain in vivo, novel imaging techniques are currently being developed. S. Burgmans and W. Backes started a pilot study on blood-brain barrier leakage in dementia (funded by an ISAO pilot award). They hypothesized increased bloodbrain barrier permeability in Alzheimer patients and developed a new dynamic contrast enhanced MRI scan. In December 2012 received a grant of 150,000 was received by these researchers to expand this research line. In 2013, Alzheimer NL will acquire additional funding (e.g. by a mailing to the donors and a spinning marathon). Research line: Determinants of normal, successful and pathological cognitive ageing P.I.: Dr. M. van Boxtel, Prof.dr. F. Verhey, Dr.ir. W. Backes, Dr. T. van Berenschot, Dr. P. Hofman, Dr. J. Jansen, Dr. S. Koehler, Prof.dr. R. van Oostenbrugge, Dr. O. Schiepers, Prof.dr. J. Wildberger PhD-students: Drs. F. van Dooren, Drs. P. Spauwen, Drs. W. van Zwam, Ir. F. van Bussel, drs. E. Zhang Focus of research: Insight into the prevention, etiology and treatment of cognitive dysfunction in the normal adult population Division staff members are active participants the Maastricht Study (MS), a study to provide more insight into the prevention, etiology and treatment of type 2 diabetes and other chronic diseases in relation to mental health. The MS illustrates the integrative approach we are aiming at, with multidisciplinary input from the departments of Psychiatry & Neurosychology, Neurology, Neuroradiology, and Neuro-ophtalmology. A grant was acquired by F. Verhey and M. van Boxtel for a 3-year s study into preventive strategies to ameliorate the individual dementia risk profile of middle-aged individuals (FP7 In-MINDD program; see www.inmindd.eu). The project by J. Jansen (VENI grant) MH&NS Annual Report 2012 12
on multi-parametric imaging of cerebral biomarkers of cognitive deterioration using MRI in diabetes type-2 in the context of the Maastricht Study was started. This project encompasses a multi-disciplinary approach between the departments of Radiology, Internal Medicine and Psychiatry & Neuropychology. Furthermore, the NWO/FES program (0,9M) aimed at the development of internet-based low-level intervention strategies to support the cognitive ageing process in middle-aged and older adults yielded its first products and results. Also, a NWO MOZAIEK talent grant was acquired to study blood brain barrier permeability in the development of cognitive dysfunction in patients with cerebral small vessel disease. Research line: P.I.: Post doc/ PhD students: Neuropsychological interventions and cognitive rehabilitation Prof.dr. C. van Heugten, Dr. M. de Vugt, Prof.dr. R. Ponds, Dr. M. van Boxtel, Dr. I. Winkens, Prof.dr. F. Verhey Drs. B. Ament, Drs. L. Boots, Drs. I. Brands, Drs. J. Collet, Drs. M. van Eeden, Drs. M. Fens, Dr. E. de Joode, Drs. R. van Knippenberg, Drs. B. ter Mors, Drs. V. Moulaert, Drs. S. Smeets, Drs. N. Tielemans, Dr. D. van Vliet, Drs. L. Willemstein, Dr. G. Wolters Focus of research: Cognitive rehabilitation and health service evaluation research. Interventions in cognitive and acquired brain disorders In this research line a strong focus is put on evidence-based neuropsychological interventions, psychosocial interventions, caregiver interventions, cognitive rehabilitation and health service evaluation research. Interventions are investigated in cognitive and acquired brain disorders. In 2012, both Prof.dr. C. van Heugten and Prof.dr. R. Ponds were appointed professor. Three PhD students finished their PhD projects successfully: Dr. E. de Joode and Dr. G. Wolters. A program on e-health intervention studies started in 2012 funded by Alzheimer Netherlands / Alzheimer Research Fund Limburg. Aim of the program is to support dementia patients and informal caregivers in their home environment. In this program 2 PhD students (L. Boots / R. van Knippenberg) study the feasibility and effectiveness of two newly developed e-health interventions. The programme will be extended to a third PhD student in 2013. A large national longitudinal study on functioning and needs in Young Onset dementia was continued in 2012 with 2 PhD students (Ch. Bakker/ D. van Vliet) and resulted in the thesis of D. van Vliet. The VSB fonds/zonmw for a research program on successful psychosocial reintegration of patients and caregivers after stroke continued in 2012. In this program 4 PhD students (Maastricht, Nijmegen and Utrecht) investigate the course and predictors of psychosocial functioning, costs of psychosocial care and effectiveness of two new psychosocial interventions for patients and caregivers aimed at self-management and cognitive behavioural therapy for post-stroke depression and anxiety. In 2012, the inclusion of patients and caregivers in a large multicentre cohort study investigating the course and predictors of psychosocial functioning was completed with 400 patients in total. The intervention protocols have been developed, and recruitment of patients started in 2012. The NWO/FES Brain & Cognition program (0.9 Me) continued in 2012 studying the effectiveness of cognitive rehabilitation and factors influencing the success of cognitive rehabilitation. In 2012, new interventions for executive dysfunctioning in Parkinson patients, errorless learning augmented Goal Management Training, problem solving MH&NS Annual Report 2012 13
therapy for stroke patients and the ABC method for severe behavioural problems after acquired brain injury have been developed, and recruitment for efficacy studies has started. Research line: Epilepsy/ neuropathy and small fiber neuropathy P.I.: Prof.dr. A. Aldenkamp, Dr.ir. W. Backes, Dr. C. Faber, Dr. P. Hofman, Dr. J. Jansen, Dr. Majoie, Dr. R. Rouhl, Prof.dr. H. Vles, Dr. M. Vaessen, Dr. M. Vlooswijk Post doc / PhD students: Drs. S. van Abeelen, Drs. E. Barendse, Drs. K. Beerhorst, drs. K. Bekelaar, Drs. R. Besseling, Drs. R. Binie, Drs. W. van Blarikom, Drs. N. Bodde, Drs. Z. Bouwman, Drs. H. Braakman, Dr. M. Buskermolen, Drs. S. Ebus, Drs. N. Gosens, Dr. J. Hoeijmakers, Drs. M. Huijts, Drs. D. IJff, Drs. R. van der Kinderen, Drs. S. van der Kruijs, Dr(s). G. Overvliet, Drs. S. Klinkenberg, Drs. J. Peijnenborgh, Drs. G. Ponds van Dijk, Drs. J. van Tuyl, Drs. T. van der Voort Focus of research: Chronic epilepsy and small fiber neuropathy Epilepsy. The central theme within the research topic Epilepsy is Chronic Epilepsy. A substantial grant from the National Epilepsy Fund (NEF) was previously obtained for this program (led by Prof.dr. A. Aldenkamp). One of the most severe consequences of chronic epilepsy concerns to the impairment of cognitive functions, including the general thinking, memory, language and problem-solving capabilities. The neuronal substrate that explains this co-morbidity is still largely unknown. The novel insight today is that epilepsy is more a network disease rather than a single focal abnormality or malfunction. Traditionally, epilepsy research utilizes different techniques and methods: measurement of brain waves (electro-encephalogaphy, EEG), imaging (acquisition of anatomic and functional brain images with scanning devices) and neuropsychological assessment. Recent technological developments of MRI methods, in particular functional and diffusion MRI, provide possibilities to obtain new insights on the organization and integrity of cerebral networks which may lead to strategies that prevent chronic epilepsy and cognitive co-morbidity. The current research program resembles a close collaboration between the Departments of Radiology and Neurology and the Epilepsy Institute Kempenhaeghe. Neuromuscular disorders. Research into neuromuscular disorders (led by Dr. C. Faber) targets myotonic dystrophy and neuropathy, with a focus on small fibre neuropathy. In 2010, a formal international cooperation within this later field was established with Prof.dr. S. Waxman (Yale University). Furthermore, a PhD was funded by the GBS CIDP Foundation International and a grant from a Baxter PNS Fellowship to start a study on clinimetric aspects (outcome measures) in Small Fibre Neuropathy (SFN) within a large multi-dimensional international multi-centre collaboration project, captured under the umbrella PeriNomS -study (Inflammatory Peripheral Neuropathy Outcome Measures Standardisation). Furthermore, additional funding was obtained from the Talecris Talents program. MH&NS Annual Report 2012 14
3.2 Division II: Mental Health Division Leader: Prof.dr. Inez Myin-Germeys Deputies: Dr. Marieke Wichers Dr. Ruud van Winkel Staff: Prof.dr. Therese van Amelsvoort Dr. Maarten Bak Dr. Philippe Delespaul Dr. Rob van Diest Dr. Marjan Drukker Prof.dr. Eric Griez Dr. Ed Goenenschild Prof.dr. Peter van Harten Dr. Gunter Kenis Prof.dr. Andries Korebrits Dr. Tineke Lataster Dr. Ritsaert Lieverse Dr. Richel Lousberg Dr. Machteld Marcelis Dr. Nancy Nicolson Prof.dr. Jim van Os Dr. Frenk Peeters Dr. Bart Rutten Dr. Jan Schieveld Dr. Jean-Paul Selten Dr. Ruud Severijns Dr. Jacqueline Strik Dr. Wolfgang Viechtbauer Prof.dr. Marten de Vries Dr. Marieke Wichers Dr. Ruud van Winkel Dr. Franz Wojciechowski Goals & Results As outlined in the SEP protocol, division II Mental Health is focusing on gene-environment research in mental health and illness, within a translational context, bringing together human and animal components of gene-environment interaction research as well as translating these findings to the clinic. The ultimate goal is to identify interactive determinants of reactive phenotypes at the level of lived experience relevant to mental health and resilience. In 2012, we worked on the following goals: 1) In order to improve G*E studies searching for the causes of complex diseases such as severe mental disorders, increasingly large sample sizes are urgently required. The EU- GEI study with 28 European partners, funded by a large FP7 grant, is half-way. The last consortium meting in Palermo in November 2012 demonstrated that the study is going well, with all centers being actively involved in data collection. Secondly, a large generalpopulation study has been set up together with the Trimbos Institute. The NEMESIS II study is collecting genetic data as well as data on mental health in 7000 participants from the general population. Division II was specifically involved in collecting data on psychosis. The second wave of this study has been finished in 2012. Third, the third wave of data-collection in the national (Amsterdam, Utrecht, Groningen, Maastricht) GROUP study has been set up. This study is following up 1000 patients with psychosis, 1000 relatives and 1000 parents and 500 controls over a period of 10 years. The last wave of data-collection has been started in 2011 and is expected to be finished in 2013. Finally, the large data-set of real-life ESM data combined with genetic information has been finalized. 2) Division II has been strongly investing in combined ESM neuro-imaging approaches (either PET, MRI or fmri). Combining imaging data with real-time and real-world personenvironment interaction patterns is extremely powerful, since it provides ecological validity for the neuroimaging data, correlating real life behaviour with alterations in specific brain regions, and vice-versa, improves the understanding the neural mechanisms underlying real-life behaviour. Division II has been setting up a large cross-diagnosis study focusing on underlying mechanisms of reward, stress and aberrant salience, studied with experimental fmri paradigms as well as real-life ESM assessment. This large SMARTSCAN project has been started in the fall of 2012. In a second study, funded by an ERC consolidator grant, the neural effects of a psychological real-life intervention will be assessed in a combined ESM PET approach. This INTERACT study will start in the beginning of 2013. MH&NS Annual Report 2012 15
3) In 2012, the PsyMate app has been developed as an assessment strategy of environmental exposures in relation to lived experience (reactive phenotytpes), relevant for mental health and resilience. The PsyMate App for IPod and Android is expected to be fully operational in 2013. In addition, a web application to provide web-based feedback will be developed. 4) Division II is continuously working to develop the PsyMate as a therapeutic tool for mental illness, such as depression and psychosis. The first, ZON-MW supported trial on depression has been finished in 2012 and showed that behavioural activation using active feedback through PsyMate is beneficial for patients with severe depression, improving real-life positive affect, activities and decreasing symptoms of depression. A second PsyMate therapy is now being developed. This Acceptance and Commitment therapy will be applied both in the SMARTSCAN and INTERACT study. 5) Translational studies bringing together basic animal research and patient studies remain a core research line within division II. The translational expert-group has initiated a number of studies, translating human findings to animal models and vice versa. 6) Division II is actively involved in forming international networks to accelerate psychiatry research. The EURON Psychiatry Institute has been formed to formalize the intensive collaboration between the University of Leuven (UPC Kortenberg) and Division II of Maastricht University. This formal collaboration will also strengthen the clinical neuroscience within EURON. Second, members of division II are active partners in the European ROAMER project, aiming to set up a European Roadmap to Mental Health Research. The methodological expert groups withing the division focus on 1) genetics, 2) Experience Sampling, 3) Neuroimaging, 4) Experimental approaches, 5) Epidemiology and Mental Health Services Research, and 6) Translational approaches. 3.2.1. Division II Expert groups Expert-group: Genetics Coordinator: Dr. R. van Winkel P.I.: Prof.dr. J. van Os, Dr. B. Rutten, Dr. G. Kenis, Dr. W. Vichtbauer, Dr. M. Drukker, Dr. M. Wichers, Dr. C. Simons, Dr. D. Collip PhD students: Drs. C. Hamels, Drs. M. Van Nierop, Drs. J. Decoster, Drs. C. Lothmann Focus of research: The design of genetic studies in the field of psychiatry as well as investigating the role of genetic variances and gene-environment interactions in the etiology, severity and course of psychopathology The genetics expert group coordinates the design of genetic studies in the field of psychiatry as well as the choice of various genetic methodologies, choice of SNPs and genes of interest for the different research lines. Furthermore, it offers a platform for bringing together several disciplines in order to conduct adequately designed, multidisciplinary and translational research to establish the role of genetic variances and gene-environment interactions in the etiology, severity and course of psychopathology and dimensions of psychological and psychiatric traits. The main focus is currently on developing polygenic risk scores. MH&NS Annual Report 2012 16
Expert-group: Coordinator: P.I.: Post doc/ PhD students: Experience Sampling Dr. M. Wichers Prof.dr. I. Myin-Germeys, Dr. T. Lataster, Dr. R. van Winkel, Dr. Ph. Delespaul, Dr. N. Nicolson, Dr. W. Viechtbauer, Dr. N. Jacobs Dr. C. Simons, Dr. D. Collip, Dr. R. Kuepper, Dr. J. Lataster, Drs. C. Lothmann, Drs. J. Decoster, Drs. C. van Zelst, Drs. F. Smeets, Drs. I. Kramer, Drs. J. Hartmann, Drs. M. Janssens, Drs. M. Gevonden, Drs. M. van Winkel, Drs. T. Batink, Drs. Z. Kasanova, Drs. J. Bakker Focus of research: To guard and increase the quality of ESM data collections and analyses, as well as to increase statistical expertise and analytic possibilities The aim of the EXM expertgroup is to guard and increase the quality of ESM data collections and analyses, to examine the validity of the method and the items used in ESM and report on this in international peer-reviewed journals, as well as to increase statistical expertise and analytic possibilities, such as time-series analysis in ESM. Expert-group: Neuro-imaging Coordinator: Dr. M. Marcelis (psychiatrist) P.I.: Dr. K. Schruers, Prof.dr. I. Myin-Germeys, Dr. E. Gronenschild, Prof.dr. J. van Os, Dr. L. Ritsaert, Dr. M. Wichers Collaborators: Dr. A. Roebroeck, Dr. M. van Kroonenburgh, Dr. P. Hofman, Prof.dr. R. Goebel, Prof.dr. K. van Laere, Prof.dr. F. Mottaghy, Dr. J. Suckling Post doc/ PhD students: Drs. P. Domen, Drs. Z. Kasanova, Drs. S. Michielse, Drs. I. Lange, Drs. C. Vingerhoets, Drs. G. Bakker, Drs. C. van der Leeuw, Drs. S. Peeters, Dr. L. Goossens, Dr. D. Collip, Drs. N. Leibold, Drs. D. Hernaus, Drs. A. Frissen Focus of research: To combine expertise on various neuroimaging modalities (eg. smri, DTI, fmri, PET, MRS) and analysing techniques to examine brain structure and function in psychiatric disorders The expert group Neuro-imaging is a group of researchers that are using various neuroimaging modalities (e.g. smri, DTI, fmri, PET, MRS) and analysing techniques to examine brain structure and function in psychiatric disorders, such as psychotic and anxiety disorder. Our main goals are to examine i) neurobiological pathways influencing psychopathology, ii) genetic and environmental determinants of brain phenotypes, and iii) neural mechanisms underlying therapeutic interventions. Expert-group: Coordinator: P.I.: Post doc/ PhD students: Experimental Psychopathology Dr. T. Lataster Dr. K. Schruers, Prof.dr. E. Griez Dr. C. Simons, Dr. L. Goossens, Drs. F. Smeets, Drs. M. Janssens, Drs. K. de Cort, Drs. I. Knuts, Drs. D. Collip, Drs. Z. Kasanova Focus of research: To design novel experimental tasks assessing underlying (neuro) psychological and biological mechanisms that are implicated in the development, course and outcome of psychiatric disorders This expert group provides support to those researchers designing novel experimental tasks assessing underlying (neuro)psychological and biological mechanisms that are implicated in the development, course and outcome of psychiatric disorders. The focus is on psychotic and affective disorders. Our goal is to combine these experimental designs MH&NS Annual Report 2012 17
with the observational methods (for example the Experience Sampling Method) that have been developed within our department in order to improve validity of our studies. Expert-group: Epidemiology and mental health services research Coordinator: Dr. M. Drukker P.I Methodology: Dr. W. Viechtbauer, Prof.dr. J. van Os, Dr. R. Lousberg, Dr. M. Drukker PI Health Services Research: Dr. M. Bak, Dr. Ph. Delespaul, Drs. G. Driessen, Dr. F. van Dael, Dr. M. Drukker Focus of research: To discuss the correct use of research methods (epidemiology) and meta-analyses as well as to work on data of patient registers and monitors This expert group aims to analyse and develop in correct use of research methods (epidemiology) and meta-analyses. Furthermore, this expert group works on the data of one register (Psychiatric Case Register) and two monitors (Cumulative Needs for Care Monitor and Medication Monitor), as well as on data of healthy children, collected by the youth health care division (YHCD) of the Public Health Service South-Limburg and the Infant Welfare Centre register. Expert-group: Coordinator: P.I.: Post doc/ PhD students: Translational and Cross-species Research Dr. B. Rutten Dr. G. Kenis, Dr. D. van den Hove, Prof.dr. H. Steinbusch, Prof.dr. J. van Os, Prof.dr. K-P. Lesch, Prof.dr. F. Verhey, Dr. K. Schruers, Dr. P-J. Visser Dr. B.e Machiels, Drs. E. Lambrichts,, Drs. L. Chouliaras, Drs. N. Leibold, Drs. S. Mafi Rad, Drs. C. Hammels, Drs. E. Pischva Focus of research: To support and stimulate innovative projects on translational research questions that require a cross-species approach The mission of this expert group / team is to support and stimulate innovative projects on translational research questions that require a cross-species approach. The research of its members aims to decipher molecular and cellular pathways that underlie sensitivity and resilience to environmental exposures, and gene-environment interactions in (neuro)psychiatric phenotypes. The ultimate goal is to identify molecular and cellular pathways that are causally involved in the etiologies of psychiatric disorders, to identify biologic markers that predict disease onset and course, to establish the reversibility of neurobiological changes, and to find novel preventive and therapeutic strategies. To this end, the team brings together multidisciplinary expertise ranging from epidemiology, genetics, molecular biology, biochemistry, experimental neuroscience, quantitative neuroanatomy, behavioral ecogenetics and clinical psychiatry. The bundling of expertise enables innovative, translational research projects on specific research questions in a variety of study group such as patients with a certain (neuro)psychiatric disorder, controls without psychiatric disorders, certain animal species, and cell cultures. Extrapolation of research findings from certain animal species to the human situation, and vice versa, is associated with numerous promises, challenges and pitfalls. The main tasks of the Expert Group are therefore i) to intensify sharing of knowledge, ii) to develop state-of-the-art methodologies, using cross-species approaches, and iii) to maximize success of such collaborative research efforts within our Research School. MH&NS Annual Report 2012 18
The team focuses on the following two main research questions: What are the neurobiological underpinnings of neuropsychiatric phenotypes; with a particular focus on mechanisms involving gene-environment interactions? What is the role of epigenetic mechanisms in mediating long term effects of environmental exposures and gene-environment interactions? These research questions are applied preferentially to the following themes which cut across the School of Mental Health and Neuroscience: i) affect regulation, ii) cognition, iii) psychosis, iv) resilience. MH&NS Annual Report 2012 19
3.3 Division III: Neuroscience Division Leader: Prof.dr. Marc de Baets Deputies: Prof.dr. Maarten van Kleef Prof.dr. Yasin Temel Staff: Dr. Daniel van den Hove Dr. Danilo Gavilanes Dr. Govert Hoogland Dr. Bert Joosten Prof.dr. Philip van Kerrebroeck Dr. Gommert van Koeveringe Prof.dr. Steijlens Prof.dr. Boris Kramer Prof.dr. L. Zimmermann Dr. Fred van Leeuwen Dr. Mario Losen Dr. Marco Marcus Dr. Piluca Martinez Prof.dr. Koo van Overbeeke Dr. Jos Prickaerts Prof.dr. Harry Steinbusch Prof.dr. Hans Vles Prof.dr. Carroll Webers Dr. Toss Berendschot Goals & Results The Division Neuroscience performs translational research with a strong emphasis on fundamental research. The translational research area can be subdivided into two parts: neurodegeneration and neuroplasticity. Its mission is to uncover the underlying mechanisms of neurodegenerative and regenerative processes for neurological and psychiatric diseases to improve early diagnosis, health and treatment strategies. Thus, we aim to gain knowledge of physiological and pathophysiological mechanisms underlying affective, cognitive and motor disorders. Within this context, the role of neuroinflammation and pain is also studied as well as their link to developmental disturbances and neuro-urogenital control. Main research topics include cell signalling, brain plasticity, neurodegeneration, regeneration,genetics and epigenetics. Its ultimate aim is to translate relevant scientific findings into new neurotherapies including pharmacotherapy, antibodies or deep brain stimulation. The multidisciplinary staff consists of professionals from relevant disciplines within research and clinic. There are collaborations within world-wide international networks of research offering a strong environment to come up with new neurotherapeutical approaches. The results of the research efforts in division 3 are described by the different Principal investigators and expertise groups. 3.3.1 Division III Research Lines Research line: Signal Transduction P.I.: Dr. J. Prickaerts, Prof.dr. H.W.M. Steinbusch Post docs: Dr. T. Vanmierlo, Dr. J. De Vry, Dr. M. van Duinen PhD students: Drs. O. Reneerkens, Drs. E. Bollen, Drs. A Sierksma, Drs. S. Akkerman, Dr. Nick van Goethem Associated Researchers: Prof.dr. Y. Temel, Dr. A. Blokland (FPN), Dr. A. Sambeth (FPN), Prof.dr. F. Verhey, Prof.dr. M. De Baets Focus of research: Cellular signal transduction in affective and cognitive processes in health and disease The major aim is to unravel the mechanism of action of signaling pathways both in health and disease while at the same time exploring the therapeutic potential of key MH&NS Annual Report 2012 20
factors in the affected signaling pathway. The focus in this respect is on the growth factor Brain Derived Neurotropic Factor (BDNF) and the second messengers camp and cgmp. In the field of signal transduction in cognitive processes/disorders we have shown that phosphodiesterase (PDE) inhibitors, which inhibit the degradation of camp and/or cgmp by PDEs, improve memory in rats independently of cerebrovascular effects. This is of major importance since this indicates that the second messengers can be targets for new drugs to improve memory function directly. Therefore, the biological mechanism of action of specific PDE inhibitors to improve memory is investigated in depth in collaboration with international academic partners (eg. University of Genoa) and pharmaceutical companies. A proof of concept study funded by a grant from ZonMW is ongoing to investigate the memory improving potential of a specific PDE type 4 inhibitor in human subjects. This is done in collaboration with Division 1 of MH&NS and the Faculty of Psychology and Neuroscience (FPN). Finally, we apply our in house developed innovative method of microelectroporation as a non-viral approach for targeted gene delivery in specific brain areas of rodents. In particular this approach has been used to directly influence the expression of BDNF receptors implicated in signal transduction in either affective or cognitive processes of a mouse model of Alzheimer s disease. This line of research was funded by the Internationale Stichting Alzheimer Onderzoek (ISAO). The results of these studies will help us to find new therapeutic targets for affective and cognitive disorders. Research line: Experimental Neurosurgery P.I.: Prof.dr. Y. Temel, Dr. G. Hoogland, Prof.dr. JJ. van Overbeeke Post doc: Dr. A. Jahanshahi PhD students: Drs. J. Carrera, Drs. S. Hescham, Drs. M. Janssen, Drs. M. Melse, Drs. B. Plantinga, Drs. S. Tan, Drs. M. Raijmakers, Drs. A. Swijsen, Drs. R. Santegoeds, Drs. L. Schonfeld, Drs. J. Smits, Drs. H. Vlamings, Drs. Y. Yakkioui, Drs. D. Zeef Focus of research: Movement disorders and related psychiatric symptoms, Epilepsy, biology of skull base tumours Our group is continuing to perform both clinical and experimental studies. In this respect, we have conducted studies to improve the surgical therapy for Parkinson s disease patients, by developing novel ultra-highfield MR-based anatomical targeting and evaluation methods (saccadometry). In our experimental studies, we mainly focused on developing novel therapies in experimental models of Parkinson s disease (tailored neurostimulation),, Huntington s disease (gene-based therapy) and tinnitus (neurostimulation). Anotherr focus of investigation is trying to understand epileptogenesis from a neurodevelopmental and inflammatory perspective. In addition, we are investigating the molecular mechanisms underlying the biological behaviour of skull base tumours such as chordoma and meningioma. These lines of research are supported by grants from the ZonMw, NWO, Cure Huntington s Disease Intitiative (CHDI, New York, USA), transnational University Limburg, Prosensa BV, and Hersenstichting Nederland. MH&NS Annual Report 2012 21
Research-Line: Transition from acute to chronic postoperative pain P.I.: Prof.dr. E.A. Joosten, Prof.dr. M. Marcus Staff-member: Dr. H. Gramke PhD students: Drs. S. van Gorp, Drs. L. Knaepen, Drs. M. Theunissen Focus of research: Identification of predictors of chronic postoperative pain and investigating approaches aimed at prevention of chronic postoperative pain Chronic postoperative pain is associated with an enormous socio-economic burden and can result from a plethora of clinical conditions. In our research, we focus primarily on trauma-induced neuropathies in the peripheral and/or central nervous system, which are a common cause of chronic pain. The initial pathological events at the site of nerve damage form the drive of pathological events higher up in the neuraxis, and are considered to be fundamental to the establishment and chronification of acute pain into chronic postoperative pain. We aim at understanding the processes of neurodegeneration and regeneration in relation to neuropathic pain. In a recently completed Ph.D. (Dr.R.Jaken) project we found that injury to peripheral nerves induces structural plasticity in the wiring of the spinal nociceptive network, a phenomenon which is likely long-lasting. In two ongoing Ph.D. projects we are investigating predictors of neuropathic pain after spinal cord injury. As a strategy to prevent pain chronification after acute nerve injury, we aim to provide (1) repair of nerve injuries / damage, (2) immuno-modulatory therapies (collaboration with Prof.dr. M. De Baets, Dr. M. Losen, Dr. P. Martinez), (3) functional training paradigms (e.g. enriched environment) and (4) the role and treatment of anxiety in development of chronic postoperative pain (collaboration with Prof.dr.M.Peeters, Faculty of Psychology). Moreover, we are interested in understanding the pathological events by which painrelated insults during the neonatal period can have long-lasting effects on pain in adulthood (Dr. J. Pawluski, Prof.dr. H. Steinbusch). Research-Line: Modulation of chronic pain P.I.: Prof.dr. E.A. Joosten, Prof.dr. M. van Kleef Staff members: Dr. M.Sommer, Dr. A.Balthazar PhD students: Drs. W. Pluijms, Drs. K. van Boxem, Drs. R. Slangen, Drs. M. van Beek Focus of research: The understanding and application of neuromodulatory techniques, in particular spinal cord stimulation and pulsed radiofrequency, in order to minimize chronic (neuropathic) pain Today Spinal Cord Stimulation (SCS) is used in the treatment of intractable neuropathic pain (NPP). Despite the existence of SCS as a pain therapy for over 40 years, up till now only two randomized clinical trials (RCT s) have been performed: one in patients with CRPS-1(Chronic Regional Pain Syndrome) and the other one in patients with Failed Back Surgery Syndrome (FBSS), both of which provide limited clinical evidence that SCS relieves neuropathic pain. We extend implementation of SCS in other NPP syndromes and designed and completed a pilot study on the clinical effect of SCS in painful diabetic polyneuropathy (PDP). As a follow-up, an RCT (Rachelle Slangen) on the effect of SCS in PDP is currently ongoing. In order to understand the underlying mechanism of action of SCS in PDP a rat model for PDP was developed in the laboratory and the effect of various stimulation parameters was analyzed. It is our intention to study the role of SCS in small fiber neuropathies experimentally as well as clinically in collaboration with Dr. C. Faber (Department of Neurology). From a basic scientific point of view the role of glial cells (as immune-regulatory cells) in the modulation of chronic pain (or plasticity of the nervous system) has our prime interest. MH&NS Annual Report 2012 22