Numerous research centres around the world have been working together in order to clarify the genetic basis of schizophrenia. The Central Institute of Mental Health (ZI) in Mannheim was also involved in the study, which was recently published online in the scientific journal Nature.
Schizophrenic disorders are complex psychiatric diseases caused by an interplay of genetic and environmental factors. Genetic studies show that 80 per cent of the variability of schizophrenic disorders are the result of genetic factors. This fact has been known for quite some time. However, molecular genetics methods have only recently made it possible to systematically search the genome for variants that modulate the risk of contracting a schizophrenic disorder. Another important area where progress has been made is in the intensive collaboration between psychiatric and genetic researchers. Thanks to international cooperation, a large number of patient and control subject samples are now available, which enable scientists to carry out genome-wide studies with a high statistical significance. Data obtained from a total of 2,663 schizophrenic patients and 13,498 control subjects were analysed by the cooperation partners and the best findings were reconfirmed by the testing of an additional 4,999 patients and 15,555 control persons.
Three groups from Germany that had already joined forces in the National Genome Research Network (NGFN) were involved in the study: the Central Institute of Mental Health, Mannheim (head of department: Professor Marcella Rietschel), the Institute of Human Genetics at the University of Bonn (research group led by Professor Markus Nöthen and Dr. Sven Cichon), and the Department of Psychiatry at the University Hospital of Munich (head of work group: Professor Dan Rujescu). These three groups had already made a major contribution to the discovery of new, rare genetic variants that contribute to the development of schizophrenia. “We have now succeeded in identifying new, frequently occurring genetic risk factors,” said Professor Rujescu. “We are getting closer to our goal of being able to prove existing hypotheses on the development of schizophrenia using molecular genetics methods,” said Professor Nöthen explaining why the genetic study carried out by an international team of researchers was so important. “The results hint at the presence of several regions in the genome that have a high probability of being involved in the development of schizophrenia,” commented Dr. Cichon.
The researchers found associations of schizophrenic disorders with several markers that comprise the MHC (major histocompatibility complex) complex located on chromosome 6. The MHC region has many genes that are of major importance for the human immune system. "These findings support a long-standing hypothesis that the immune system plays a role in the development of schizophrenic psychoses," said Professor Rietschel. This hypothesis is based, for example, on clinical observations that virus infections contracted in the last trimenon of pregnancy are associated with a higher number of babies who will later contract schizophrenia. It is also based on earlier reports on the coupling and association of markers of the MHC region with schizophrenia.
The study also provided evidence pointing to the involvement of genetic variants in the neurogranin gene located on chromosome 11q24.2 and the transcription factor TCF4 on chromosome 18q21.2 in the development of schizophrenia. These genes are involved in metabolic pathways that play a role in brain development, memory and cognition. The major symptoms of schizophrenia are disorders of the brain and cognition along with other generally known phenomena such as delusions and hallucinations. The authors hope that their findings will give them new starting points for developing innovative therapies.
Further information: Central Institute of Mental HealthProf. Marcella RietschelDepartment of Genetic Epidemiology in PsychiatryJ5, 68159 MannheimTel.: +49 (0)621 / 1703-6051E-mail: marcella.rietschel(at)zi-mannheim.deAdvanced Online Publication in "Nature" on 1 July 2009:Common variants conferring risk of schizophrenia. H. Stefansson et al. (10.1038/nature08186)