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Unusual chromosomal changes increase the risk of schizophrenia

31.07.2008
People with schizophrenia have an increased number of unusual chromosomal changes, particularly structural changes that have the potential to alter the function of the genes. These results were published today in the scientific journal Nature.

Research scientists found changes in the structure of the genes in patients with schizophrenia when they studied what are known as copy number variants.

Genetic diseases are caused by a large number of different possible changes in human DNA. The type of mutation or change referred to as CNV means that large pieces of DNA may exist in several copies, have disappeared or have been transposed. In some diseases such changes in the genome may be protective, for example in HIV infection and malaria.

“The results strongly support the notion that schizophrenia may be partly caused by the effects of such structural changes in genes, both across the whole genome and in specific chromosomes,” says Christina Hultman, associate professor at Karolinska Institutet.

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A breakthrough in genetic research on diabetes and prostate cancer, among other diseases, has been achieved in 2007 and 2008 by mapping the whole genome in what are known as genomwide association studies. There is now much to suggest that a breakthrough may also be made in schizophrenia in 2008, when up to seven studies relating to a total of 20,000 cases have been carried out. An important step will then be to understand the biological mechanisms underlying a complex pattern of genes that can be linked to schizophrenia and also what is known as epigenetics, that is to say how genes are switched on and off during the lifespan.

“We anticipate a breakthrough in the near future in research into psychiatric diseases such as schizophrenia, bipolar disease and autism. At the same I wish to stress that in such a complex disease as schizophrenia there is a need for research on both genetic and environmental causes and on treatment and management,” says Christina Hultman.

Schizophrenia is a common psychiatric disease. There are around 35,000 people in Sweden today who have at some time been in institutional care with the diagnosis of schizophrenia, and just as many who have been treated for other psychotic diseases.

It has long been known through family studies, adoption studies and twin studies that there appear to be hereditary causes of schizophrenia. The risk among both first-degree relatives (a person’s children) and second-degree relatives of people with schizophrenia is raised. The search for specific genetic causes in the last ten years has been intensive, but schizophrenia has a complex pattern of heredity, and the results of previous studies have been unclear. Various research teams have presented several different suggestions for genes that may be involved, including genes that control the development of brain cells.

Publication: “Rare chromosomal deletions and duplications increase risk of schizophrenia”, International Schizophrenia Consortium, which includes Christina Hultman from the Department of Medical Epidemiology and Biostatistics of Karolinska Institutet. Nature on line, www.nature.com, Digital Object Identifier (DOI): 10.1038/nature07239.

Sabina Bossi | alfa
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