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Genetic Epidemiology in Psychiatry

Head

Scientific Director

Prof. Dr. Marcella Rietschel

Phone: +49 621 1703-6051

Fax: +49 621 1703-6055

e-mail

Assistant: Viola Lahr
Phone: +49 (0) 621 1703-6052, e-mail

Laboratory Building, 4th Floor, Room 406

Description

The Department of Genetic Epidemiology in Psychiatry investigates the biological and environmental basis of psychiatric illness, as well as gene-environment interactions and the genetic basis of treatment response. Since psychiatric-genetic research touches upon a range of ethically sensitive issues, the Department is also engaged in intensive scientific dissection of the inherent ethical dilemmas.

Subject areas and research focus of the department:

  • Phenotype characterization: intensive, longitudinal phenotyping with the simultaneous assessment of environmental factors („deep phenotyping“)
  • Biobank
  • Genetic and biostatistical analysis
  • ELSI (ethical, legal and social implications of genetic and genomic research for individuals, families and communities)

Phenotype characterization:
The Department has one of the largest psychiatric phenotype-databases. This comprises comprehensively characterized samples of patients with psychiatric illness, their relatives and controls, as well as individuals from the general population.

One of our central research themes is treatment response and the acquisition of prospective intensive longitudinal data (ILD). Here, we implement ambulatory assessment (AA) to track complex phenotypes (RDoC) over time. Using multimodal, longitudinal assessments, we aim to identify markers which help not only characterize response to various interventions, but which also may predict response itself. We aim to find biobehavioural markers of emotional, cognitive and mental/disease state as well as sensitive predictors of changes and transitions between these states. In particular, we are in the process of employing novel digital assessment technologies (such as continuous locomotor activity assessment and audio/visual recording) to study and quantify potential quick-acting interventions (e.g. Depression: sleep deprivation, electroconvulsive therapy; Addiction: oxytocin and other pharmacotherapies) and inform the search for underlying mechanisms. In addition, we are working with experts in various fields (i.e. signal processing, engineering, informatics) to find and develop new ways to leverage the rich data streams being assessed.

Biobank:
A prerequisite for psychiatric genetic research is the availability of a comprehensive collection of biomaterials.

Genetic analyses:
Genome wide genetic and epigenetic investigations are conducted in collaboration with Bonn and Munich. Replication studies (Quant Studio, Pyromark), NGS (e.g. microbiome), mobile real-time sequencing (Nanopore) for on-site therapy management and direct feedback to patients are conducted in our Molecular Genetic Laboratory.

Biostatistical analyses:
To develop and establish biomarkers and algorithms, we pursue innovative analysis-strategies of omics-data generated from our well-characterized samples. Here, we focus on the comprehensive integration of phenotypic ILD, molecular, genetic, metabolomics and microbiome data collected and generated at the Department integrating the rapidly growing information from publicly available “-omics”-data. A special focus will be on leveraging the power of both large and longitudinal data sets, including longitudinal “–omics” data, to explore their trajectories. While most research to date has necessarily been cross-sectional in nature, advances in methods and technology are increasingly pointing to the value of time-sensitive and time-based measures to study the dynamical courses of disease progression. These analyses are expected to capture underlying “disease dynamics” which have so far been missed.

The Department will dissect trajectories of “-omics” data in a translational approach by making increased use of multivariate machine-learning approaches and network/graph analysis models in order to overcome the limitations of traditional statistical and genetic analysis packages and facilitate the exploration of high dimensional data. These are developed in collaboration with partners from the CIMH (RG Translational Bioinformatics in Psychiatry, Dept. of Theoretical Neuroscience) and external collaborating partners (e.g. Institute of Computational Biology, Helmholtz Centre Munich; Tim Hahn, Goethe University Frankfurt). Integration of “-omics” data from different sources will allow novel insights into disease etiology (e.g. multi-omics analyses in human postmortem brain tissue).

Statistical approaches using the wealth of genome-wide data such as polygenic risk scores (PRS) explain increasing shares of the genetic risk for psychiatric disorders. By our contribution to international GWAS consortia such as the Psychiatric Genomics Consortium (PGC), we contribute to the large data sets necessary to allow reliable prediction. The ongoing effort and our ongoing contribution to those consortia, will allow more reliable and more specific signal to be incorporated into PRS. PRS screening could serve as a marker to identify individuals at increased risk for specific disorders, and the implementation of prevention programs. Future GWAS will not only be targeting disease risk per se, but also important underlying features, e.g. treatment response to specific medication. Identifying determinants of treatment response can guide the selection of individually tailored treatments, and has the potential to significantly improve treatment outcome.

We will extend the concept of polygenic risk scores, to epigenetic whole-genome methylation data, to investigate sex-specific risk mechanisms for depression. This will be done in cooperation with the KORA study, Moshe Szyf (University of Montreal, the pioneer in the field of epigenetics).

The Department is also engaged in regular exchanges with other experienced analysts worldwide, as well as in the continuous development of approaches and practices.

ELSI: ethical, legal and social implications of genetic and genomic research for individuals, families and communities:
Since this research has many ethical-, legal-, and social implications, the Department also works to address these issues. Besides theoretical considerations, the Department seeks to formulate practical solutions to such questions within the research context, e.g., data protection and the optimal provision of information to patients. Here, a key focus is on the examination and harmonization of the procedures of national and international cooperation partners, keyword: “Global Science-Global Ethics”.

The Department collaborates with representatives from diverse disciplines, e.g., with lawyers, ethicists, philosophers, and patient representatives. In addition, Marcella Rietschel and her team are active members of the Task Force on Genetic Testing of the International Society of Psychiatric Genetics, and provides advice on ethical issues to both national- (e:Med Systems Medicine: Datenschutz und Ethik, TMF e.V.:Biomaterialbanken) and EU-funded projects (Imagemend, PRISM, MiND).

Prof. Dr. Ole A. Andreassen, Institute of Clinical Medicine, University of Oslo, Norway

Dr. Markus Baumgartner, Institute of Forensic Medicine, Universit of  Zurich, Switzerland

Prof. Dr. Dr. Konrad Beyreuther, Network Aging Research (NAR), University of Heidelberg

Dr. Dr. Elisabeth Binder, Max-Planck-Society, München

Prof. Dr. Sven Cichon, University Basel, Switzerland

Prof. Dr. David Collier, William Harvey Research Institute, Barts and The London, UK

Prov.-Doz. Dr. med. Joachim Cordes, LVR-Clinic Düsseldorf

Prof. Dr. Dr. Udo Dannlowski, Department of Psychiatry, University Münster

Prof. Dr. Maria Grigoroiu-Serbanescu, Medical University Bucharest, Romania

Lejla Hasandedić, Akdeniz University, Ankara, Turkey

Dr. Patrick Jern, Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland

Prof. Dr. Rudolf Kaaks and Prof. Dr. Hermann Brenner, German Cancer Research Center,  (DKFZ) Heidelberg

Prof. Dr. Tilo Kircher, University Clinic of Psychiatry and Psychotherapy, University of Marburg

PD Dr. Dirk Lanzerath, German Reference Centre for Ethics in the Life Sciences (DRZE) Bonn

Prof. Dr. Nick Martin, QIMR Brisbane, New Zealand

Prof. Dr. Fermin Mayoral Cleries, Institute of Biomedical Research, Malaga, Spain

Prof. Dr. Peter McGuffin, Institute of Psychiatry, King’s College London, UK

Professor Ole Mors, Prof. Dr. Preben B. Mortensen und Dr. Christiane Gasse, Abteilung für Psychiatrie, Aarhus Universität, Dänemark

Prof. Dr. Hossein Najmabadi, Universität für Soziale Wohlfahrt und Rehabilitationswissenschaften (USWR), Teheran, Iran

Prof. Dr. Markus Nöthen, Institute of Human Genetics, University Clinic, Bonn

Prof. Dr. Stephan Ortner und Prof. P.P. Pramstaller, Europäische Akademie Bozen, Italien

Dr. Lilijana Oruc, Universität Sarajevo, Bosnien und Herzegowina

Prof. Dr. Dan Rujescu, Universitätsklinikum Halle

Dr. Christoph Schickhardt und Dr. Romy Kirsten, NCT, Universität Heidelberg

Prof. Dr. med. Peter Schirmacher, Pathologisches Institut, Universität Heidelberg

Prof. Dr. Thomas Schulze und Prof. Dr. Peter Falkai, LMU München

Prof. Dr. Ze’ev Seltzer und Prof. Dr. James L. Kennedy, Universität von Toronto, Kanada

Prof. Dr. Birgit Spinath, Institute of Psychology, Universität Heidelberg

Prof. Dr. Kári. Stefánsson, Decode Genetics, Island

Dr. med. Patrick Sullivan, Abteilung für Genetik, Universität von North Carolina, USA

Prof. Dr. Moshe Szyf, Abteilung für Pharmakologie und Therapie, McGill Universität, Kanada

Prof. Dr. theol. Klaus Tanner, Wissenschaftlich-Theologisches Seminar, Universität Heidelberg

Dr. Alexander Varzari, Institute für Phthisiopneumologie, Kishinev, Moldawien

Prof. Dr. Dr. Henrik Walter, Dr. Dr. Stephan Ripke und Prof. Dr. Dr. Andreas Heinz, Charité Berlin

Dr. James Walters, Institut für psychologische Medizin und klinische Neurowissenschaften, Cardiff Universität, UK

Prof. Dr. Dr. Erich Wichmann, Helmholtz-Zentrum, München

Prof. Dr. Georg Winterer, Medizinische Fakultät, Universität Düsseldorf
 

Topics of the department

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4 pillars of the department

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Deep Phynotyping

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Zentralinstitut für Seelische Gesundheit (ZI) - https://www.zi-mannheim.de