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Molecular psychiatry

Head: Prof. Dr. med. Helge Frieling

English version

Background

The Molecular Psychiatry research group focuses on questions of neuroepigenetics.

Epigenetic mechanisms serve to regulate genetic activity and are partly hereditary. DNA methylation and post-translational modification of histone proteins can change the structure of DNA (chromatin remodeling) in such a way that individual genes are permanently switched off. Short RNA species and post-transcriptional RNA modifications (RNA editing; alternative splicing) are further substrates of epigenetic processes.

In psychiatry, the particular importance of epigenetic processes in the development, maintenance and healing of mental illnesses has been demonstrated in recent years, as well as for the biological coding of susceptibility to illness (vulnerability) or insusceptibility (resilience). Epigenetic processes are also of particular interest for the transmission of mental illnesses over several generations.

To research these phenomena, we at the Laboratory for Molecular Neuroscience we use modern cell biological and biochemical methods in addition to the entire spectrum of molecular biological methods. The investigation of epigenetic processes from cell culture through suitable animal models to clinical study populations corresponds to our guiding principle of translational research.

Within the Clinical Department of Psychiatry, Social- and Psychological Therapy, we work closely with the following research groups

Overarching goals

Mapping precision in psychiatry: yesterday, today, tomorrow. From epigenotyping to clinical application to precise diagnostics and therapy.
Precision Psychiatry /Copyright: Prof. Dr. med. H. Frieling, MHH

One of the main obstacles in psychiatric research today is the obvious discrepancy between the diagnostic categories that were mainly coined at the end of the 19th century and the modern neurobiological concepts of normal and disturbed brain function, which leads to a delay in the development of new and more effective therapies.

One approach to bridge this gap is offered by "personalized" or "precision psychiatry", which will identify more homogeneous subgroups of mentally ill patients on the basis of a bio-psychosocial model of disease and provide them with specific therapies. A major research goal of our research group in this context is the use of epigenetic markers to identify and categorize biologically distinct subgroups of psychiatric disorders, using response to specific therapies as the primary phenotype. Once a potential marker is discovered, we not only address rigorous replication in clinical cohorts, but also try to understand how specific regulation of a particular gene leads to (non-)response to specific therapies. To answer these questions, we use patient-derived samples including induced pluripotent stem cells (iPSC) and post-mortem brain tissue in addition to animal and cell culture models and utilize a broad spectrum of state-of-the-art molecular testing methods.

Our molecular findings complement imaging, psychopathology, test psychology and other clinical data from patients, as even the best molecular analyses in psychiatric disorders need to be informed by the Clinical Department and should subsequently be able to be transferred back to the clinic. To enable this flow, large cohorts of patients with excellent and multimodal phenotyping are needed. One way to recruit these cohorts is to establish a broad-consent system that allows the use of all routinely collected clinical data. Facilities or Institutions of a data warehouse system will allow all data from the clinical information systems to be used for specific research questions.

We have supplemented this system with large patient registries for specific indications (for example, a registry for the special outpatient clinic that treats patients with Prader-Willi syndrome and psychiatric disorders) or therapies (Lower Saxony ECT Outcome Registry - NEKTOR) or side effects (AMSP; pharmacovigilance in gerontopsychiatry) and expanded it to include biobanking of blood and other samples according to strict pre-analytical protocols. To achieve high quality phenotypic data, we have implemented standardized diagnostic and treatment algorithms. These algorithms can be easily adapted to incorporate new findings (for example, potential new biomarkers that guide treatment). At the same time, large patient collectives open up the possibility of tracking new findings from basic research, such as structural variations of the genome in people suffering from psychosis, and better understanding and making them clinically useful through multimodal reverse phenotyping.

Large amounts of data from the various areas of basic research (-omics, imaging) or clinical research contain a wealth of information. In addition, new developments in sensor technology (e.g. wearables) or app-based examinations as well as the possibility to use all clinical data from routine care lead to an even more extensive amount of data that can no longer be handled with classical evaluation methods of inferential statistics. In order to access this information, new methods for data analysis such as pattern recognition based on artificial intelligence / neural networks are necessary.

In recent years, we have gained experience in using these "big data" methods for the integrative analysis of molecular and clinical data. The use of self-learning algorithms not only helps to discover new and unexpected relationships between molecular and clinical data, but also promotes the development of diagnostic and treatment algorithms in an iterative and evolutionary way (Plan-Do-Check-Act (PDCA) cycle to integrate patient care and research goals), paving the way for more precise psychiatry.


Scientific collaborations

In addition to the above-mentioned internal departmental collaborations, we work with numerous other research groups within the framework of national and international research networks (e.g. on eating disorders [BMBF-EDNET], borderline personality disorders, psychopharmacological effects [BMBF-NeSSy] and traumatization):

Research group members

Head of the research group

Prof. Dr. med. Helge Frieling

Deputy Head of Clinic

Phone: +49 511 532 7275

Fax: +49 511 532 7276

frieling.helge@mh-hannover.de