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Advances in the field of schizophrenia research: New genetic factors identified

Schizophrenia is one of the most serious mental illnesses and is accompanied by symptoms that include delusions and blunted affect. Environmental as well as genetic factors form a complex interplay that leads to the illness. Two papers published in the Internet editions of the professional journals "Nature" and "Nature Genetics" have offered a ground-breaking step in the complex and extraordinarily difficult search for relevant genetic factors. The studies were carried out by large international research teams that also included researchers from Ludwig-Maximilians-Universitt (LMU) Mnchen. As one of the first authors of the "Nature" study, Dr. Dan Rujescu, along with his colleague Dr. Hreinn Stefansson from deCODE genetics and Dr. Sven Cichon from the University of Bonn, played an influential role in conducting the studies. In both studies, researchers analyzed and compared the genetic data of non-affected persons with persons suffering from schizophrenia in the hopes of discovering genetic variations that contribute to the illness. "We were able to identify three so-called microdeletions." reports Rujescu. "When one of these rare genetic variations is present in a person, the result is a moderate to large increase in disease risk. In a study lead by Dr. Michael O'Donovan from Cardiff University we also found other relatively frequent variations that slightly increase a person's risk. Our results could make a significant contribution to the further research concerning the causes of schizophrenia as well as the development of diagnostic testsand possibly treatment."

Contrary to common belief, a split personality is not one of the potential symptoms of schizophrenia. "Persons affected with the illness, however, may exhibit changes in thought and behavior," explains Dan Rujescu, head of the Molecular and Clinical Neurobiology Section at the Department of Psychiatry, University of Munich. "Hallucinations or delusions are only a few of the potential symptoms of this severe mental illness." Symptoms may also include a blunted affect along with episodes of depression. Depending on the manifestation, schizophrenia is classified into different subtypes. Altogether, the illness is among the most severe mental illnesses known. According to estimates, approximately one in every hundred persons experiences a schizophrenic episode at least once in their lives. In Germany alone there are approximately 800,000 persons affected with the illness. It is still only possible to partially treat schizophrenia. In a best case scenario, such treatment can offer a patient a good level of functioning despite the illness.

What exactly causes schizophrenia remains unknown. Family, twin and adoption studies have demonstrated, however, that in addition to environmental factors, genetic components are crucialapproximately 80 percent according to estimations. Thus, close relatives of a schizophrenic patient are more susceptible to fall ill themselves. The hereditary pattern of the underlying genetic factors, however, proved extraordinarily complex and can be decoded only with great difficulty. "There are presumably several genetic factors working together, each of which only has a very small effect on disease risk or which occur very rarely and have a moderate to strong effect," explained Rujescu. "For this reason, the field of schizophrenia genetics should be concerned with identifying these so-called risk genes. We have certainly made an important leap in the search for genetic factors. Yet there is not a single 'schizophrenia gene' but rather only genetic variations that can increase or decrease one's susceptibility to the illness."

The European team of researchers who conducted the "Nature" study compared the genome of thousands of persons not affected by the illness with those patients suffering from the disease. The researchers sought to discover what are known as "copy number variations" or CNVs. These are sections of DNA with at least 100,000 building blocks that vary among different people particularly with respect to the number of copies found in the person. The scientists were able to identify three especially important CNVs, one of which is found on chromosome 1 and the other two on chromosome 15, respectively. These CNVs proved relevant to the risk of developing schizophrenia and other related psychoses. The second study examined what are known as single nucleotide polymorphisms (SNPs). These are the smallest possible genome variations that affect the individual building blocks within the entire genome. The researchers were able to identify several DNA locations where SNP variations that lead to an increased risk of developing a psychosis such as schizophrenia occur.

Certain SNPs and CNVs associated with schizophrenia had already been discovered prior. However, these studies were only based on the genetic data of a relatively small number of persons. In contrast, the newly published studies were based on the data of thousands of persons. "Altogether, a great number of institutes took part in both studies," reports Rujescu. "We would never have been able to achieve the enormous sample size otherwise and were therefore able to find associations between the genetic variations and the illnesswithout regional or national differences. What is also particularly interesting here is that there are clearly different mechanisms that come into play. For example, we have found rare genetic variations that have a major influence, but we have also found frequent genetic variations that have only a minor effect on the disease risk."


Contact: Luise Dirscherl
Ludwig-Maximilians-Universitt Mnchen

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