The Research Group Molecular Psychiatry

Rsearch Group Leader: Prof. Dr. med. Helge Frieling

Background

The Research Group Molecular Psychiatry is mainly focused on neuroepigenetics.

Epigenetic mechanisms serve to regulate transcriptional activity and are partly hereditary. Through DNA methylation and post-translational modification of histone proteins, the structure of DNA can be altered (chromatin remodeling) in such a way that individual genes are switched on and off in a spatio–temporal manner. Short RNA species and posttranscriptional RNA modifications (RNA editing; alternative splicing) are further substrates of epigenetic processes. Environmental cues (stress, diet, substance abuse and adverse life experiences) mediate their effect on cellular pathways via epigenetics.

Therefore, the special importance of epigenetic processes in psychiatry has been demonstrated both in disease development, maintenance and cure of mental illness, and in the biological coding of disease susceptibility (vulnerability) or insusceptibility (resilience).  Epigenetic processes are also of particular interest for the longitudinal transmission of mental illness over generations.

To investigate these phenomena, we in the Laboratory of Molecular Neuroscience use an entire spectrum of molecular biological methods as well as modern cell biological and biochemical processes.

We systematically design and execute clinical studies followed by validation in cell culture and animal models towards our mission statement of translational research.

Within the Department of Psychiatry, Social Psychiatry and Psychotherapy there is close cooperation with the research groups

  • Alcohol, Nicotine and Drug Addiction
  • Neurometabolism and Psychotherapy
  • Depression and ECT
  • clinical psychology and sexual medicine

Aim of the research group

One of the main obstacles in today's psychiatric research is the apparent discrepancy between the diagnostic criterias, mainly coined at the end of the 19th century, and modern neurobiological concepts of normal and impaired 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 disease model and will provide these specific therapies. In this context, a major research goal of our research group is the use of epigenetic markers to identify and categorize biologically different subgroups of psychiatric disorders, using response to specific therapies as a primary phenotype. Once a potential marker is discovered, we not only focus on 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 animal and cell culture models as well as patient samples including induced pluripotent stem cells (iPSC) and post mortem brain tissue, and employ a broad spectrum of state-of-the-art molecular testing methods.

Reterospectively, Our molecular findings are complemented with functional imaging, psychopathological, test-psychological and other clinical data of the patients*, because even the best molecular analyses of psychiatric disorders need to be informed by the clinic and should be transferable back to the clinic afterwards. 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-content system that allows the use of all routinely collected clinical data. By establishing a data warehouse system, all data from the clinical information systems can be used for specific research questions. We have supplemented this system with large patient registries for special indications (for example, a registry for the special outpatient clinic that treats patients with Prader-Willi syndrome and psychiatric disorders), therapies (Lower Saxony EKT-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. In order to achieve a high quality of phenotypic data, we have implemented standardized diagnosis and treatment algorithms. These algorithms can be easily adapted to incorporate new findings (e.g. potential new biomarkers guiding treatment). At the same time, large patient* collectives open up the possibility to understand new findings from basic research, such as structural variations of the genome in people suffering from psychosis, and to better understand and clinically exploit them through multimodal reverse phenotyping.

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

In recent years we have gained experience in the use of 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 diagnosis and treatment algorithms in an iterative and evolutionary way (Plan-Do-Check-Act (PDCA) cycle to integrate patient care and research goals), thus paving the way for more precise psychiatry.

Research group leader

Prof. Dr. med. Helge Frieling

Hanover Medical School

Center for Mental Health

Laboratory for Molecular Neuroscience

Founding member and scientific advisory board of the Research Core Unit Genomics of the MHH

Feodor-Lynen-Str. 35

30625 Hannover

 

Phone 0511 532 7275

Fax 0511 532 7276

frieling.helge@mh-hannover.de

 

Colleagues