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Photo: Henseler, Copyright: BMBF
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The genetic-epidemiological research group deals with the identification of genetic and environmental causes of mental disorders. Furthermore, the genetic contributions on the individual response of psychopharmacological drugs are explored. Our main focuses of interest are affective and schizophrenic disorders.
In line with the current knowledge we can assume that both the aetiology of the disorders and the treatment response are determined by the interaction of genes and environmental factors. As in all complex disorders, the effect of single vulnerability genes is thought to be limited. Thus, large patient samples are necessary to identify the underlying susceptibility-genes.
The homogeneous and standardized clinical characterisation of these patients is an important prerequisite for genetic analyses. Following previous work of the research group of Prof. Dr. Marcella Rietschel at the Psychiatric Hospital at the University of Bonn (Head: Prof. Dr. Wolfgang Maier), a coordinated examination of large samples will be conducted within the so-called "PsychoGene" - network. This network is organised by the Bonn and Mannheim groups. Further partners are the Psychiatric University Hospital of the Saarland in Homburg (Head: Prof. Dr. Peter Falkai) and the Psychiatric University Hospital of Göttingen (Head: Prof. Dr. Eckart Rüther).Research focuses:
Genetics of schizophrenic and bipolar affective disorders
Schizophrenic and bipolar affective disorders are severe and common disorders. The biological basis of these disorders is still widely unknown and no causal therapy is available yet. Formal genetic analyses have shown that genetic factors contribute to 50-80% of the variance in the aetiology of the disorders. In classic-genetic (so-called monogenetic) disorders one single gene is responsible for the manifestation of the disorder. However, in psychiatric disorders this is different. The susceptibility to these disorders is not determined by a single gene locus, but rather by several so-called vulnerability (disposition-, or susceptibility-) genes. Each of these genes may neither be necessary nor sufficient to cause the disease and genes may interact with each other and/or with environmental factors.
For the localisation of chromosomal regions which might harbour genes for the development of a disorder, so-called linkage analyses have been performed. For these analyses, the availability of families with several affected members is a prerequisite. For bipolar affective disorders we have conducted a genome-wide linkage analysis and have identified different regions on the human genome, in which vulnerability genes are very likely to be localised (Cichon et al. 2001). To characterise the responsible genes on a molecular level we now have to further analyse these chromosomal regions, i.e. embark on fine-mapping procedures. For this purpose both case-control and family-based association studies provide promising tools (Schulze and McMahon, 2002). The success of these approaches, however, hinges critically on the availability of both large sample sizes and on exact and detailed phenotype-characterisation. Pharmacogenetics
Genetic factors also play an important role in the way individuals respond to psychopharmacological drugs and develop specific side effects. A main goal of our research is to identify these genetic factors on a molecular level in order to be able to predict response and the risk of developing side effects even before starting medication. This will allow more efficient treatment with less side effects and higher compliance in patients.
Environment and Genes
Besides genes, environmental factors also contribute in a major way to the development of schizophrenic and affective disorders. We believe that as soon as genetic risk factors will be known, this will allow the identification of both preventive and unfavourable environmental influences. Thus a comprehensive evaluation not only of the clinical course of the disease but also of a multitude of environmental and life history-related factors is warranted. Ethical aspects of psychiatric-genetic research
Investigating the molecular genetic basics of psychiatric disorders raises ethical questions. To address this topic we additionally focus on the chances and risks associated with psychiatric-genetic research. We pursue these questions within the framework of several research projects. |
