Wednesday, 5 October 2016

Schizophrenia: genes under the microscope to identify molecular triggers

The University of Trento is part of the “CommonMind Consortium” with Enrico Domenici of CIBIO. The first results of their work have been published in “Nature Neuroscience”.

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Different genes might be associated with schizophrenia, but recent studies point in the direction of at least three genes, and some other factors, that make us vulnerable to this disease. In the near future, this discovery might lead to the development of new treatments.

Looking into the microscope is an international group of researchers, and one of them is Enrico Domenici of CIBIO, the Center for Integrative Biology of the University of Trento.

«Thanks to recent advances in genomics – says Domenici (Laboratory of Neurogenomic Biomarkers, CIBIO) – we now know that there are many subtle variations, in over 100 different genomic regions, that may increase a person’s risk of developing this highly disabling disorder in their life. But very little is known on how these variations exert their effects».

The researchers’ work started four years ago with the establishment of an international consortium, the CommonMind Consortium, made up of scientists from nine institutions and four different countries, thanks to public and private funds. The aim of the consortium was to decipher the molecular mechanisms at play in the brain of patients with mental disorders and make this data broadly available to the scientific community.

On 26 September “Nature Neuroscience” published an article, “Gene Expression Elucidates Functional Impact of Polygenic Risk for Schizophrenia”, describing the first steps towards the identification and unmasking of the genes that might be responsible for the disease.

Domenici explains: «We started from the analysis of post mortem brain tissue from over 600 schizophrenic patient and healthy donors. Thanks to advanced sequencing and data analysis technologies, we were able to identify, in the 100 different genomic regions, a series of genetic variants responsible for changes in cerebral processes at molecular level. With more accurate analysis, we have finally identified five suspect genes and by testing them in cellular and animal models, we found that three of them induced deficits that are similar to those found in tissues from schizophrenic patients. This achievement opens new perspectives to understand the genetic mechanisms that, together with other factors, contribute to the development of schizophrenia. The research work continues: by monitoring the activity of these genes we hope to develop new therapeutic treatments».